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Biomedical subjects

J Ladefoged

Publications and source records attributed to J Ladefoged.

At least 55 records · Page 3Linked to original sources
PubMed1988

In vitro immune functions in patients with minor, moderate, and severe kidney impairment.

We examined the in vitro immune response of lymphocytes from 86 non-dialyzed patients with progressive renal failure and 48 healthy control subjects by comparing the production of interleukin-2, the mitogen-induced proliferative response and sensitivity to glucocorticoid of lymphocyte cultures. The patients were divided in three groups with minor, moderate, and severe uremia. The uremic lymphocyte responses to stimulation with concanavalin A (Con A) were significantly lower than those of control lymphocyte cultures. A similar but not significant decrease was also seen in phytohemagglutinin (PHA) and pokeweed mitogen stimulated cultures. There was no trend towards diminishing mitogen responses with decreasing renal function. The median interleukin-2 activity in the uremic cell cultures was decreased by 50% during the culture period but the decrease was not significant. However, PHA and Con A stimulated lymphocyte cultures from all groups of patients were significantly more sensitive to the immunosuppressive effect of methylprednisolone. Thus an increased sensitivity to the immunosuppressive effect of glucocorticoid can be demonstrated in vitro at an early stage of progressive renal disease.

Adolescent↗
PubMed1988

Focal segmental glomerular tip lesions with IgM. A case report.

In a 59-year-old man with nephrotic syndrome, immunohistochemical examination of a renal biopsy revealed exudations of IgM localized to peripheral segments of the tufts in some glomeruli. This pattern is known so far to occur only in some cases of focal segmental glomerulosclerosis (FSGS). In this patient, however, no histological criteria of FSGS were present, nor was the clinical course typical of this disease, being characterized by changing reactions to steroid therapy. The patient was therefore considered to suffer from a disease different from FSGS. The histological lesion may possibly be identical with what has recently been described as the glomerular "tip lesion".

Biopsy↗
PubMed1987

Lithium: long-term effects on the kidney--II. Structural changes.

Forty-six patients treated with lithium for an average of 8 yr participated in a follow-up study involving a kidney biopsy. The results were compared with renal biopsy specimens from an age-matched group of controls never treated with lithium. The average number of totally scelerotic glomeruli and atrophic tubuli was higher in lithium-treated patients. The histopathological changes showed significant correlations with lithium dosage schedule. Both the proportions of sclerotic glomeruli, atrophic tubuli and focally distributed interstitial fibrosis were higher in patients receiving their lithium two or three times a day than when lithium was given in a single daily dose.

Adult↗
PubMed1987

Urinary prostaglandin E2 excretion in renal allotransplantation in man.

The urinary prostaglandin E2 excretion was measured daily for 28 days in 15 patients (10 men and 5 women) after renal allotransplantation. Patients with acute oliguric renal failure immediately after the transplantation showed high urinary PGE2 concentrations, but no or minimal increase in the total excretion rates. The median PGE2 excretion was 211 micrograms/24 h after establishment of stable renal function, but with great individual variations. Rejection crises were characterized by a two-fold increase in PGE2 excretion, with a subsequent fall induced by the steroid treatment. The PGE2 excretion correlated better with urinary sodium excretion than diuresis.

Acute Kidney Injury↗
PubMed1987

The immunosuppressive potency in vitro of physiological and synthetic steroids on lymphocyte cultures.

The immunosuppressive potency of five natural and seven synthetic steroids were tested in vitro on phytohemagglutinin (PHA) stimulated peripheral lymphocytes (PBL) and T-lymphocytes and compared to their anti-inflammatory potencies. The physiological glucocorticoid, hydrocortisone, was of intermediate immunosuppressive potency in vitro, whereas the metabolites of hydrocortisone (cortisone, dihydrocortisol, and tetrahydrocortisol) and aldosterone were without effect. The synthetic steroids, methylprednisolone and fluorohydrocortisone were both highly potent in suppressing the PHA responses of both lymphocyte subsets. Prednisolone and dexamethasone were of intermediate potency and ranked similar to hydrocortisone which is in contrast to their anti-inflammatory properties. Prednisone, the biologically inactive metabolite of prednisolone, was without immunosuppressive properties. Deoxy-deflazacort, the biologically active metabolite of deflazacort (a new oxazoline derivative of prednisolone) was comparable to prednisolone and hydrocortisone in suppressing lymphocyte proliferation but again there was a large discrepancy between the in vitro immunosuppressive effect and the anti-inflammatory potency. In conclusion, the present assay may therefore separate the immunosuppressive properties from the anti-inflammatory properties of glucocorticoids. These findings may be useful for comparison of new synthetic steroids.

Adult↗
PubMed1987

The impact of high lymphocyte sensitivity to glucocorticoids on kidney graft survival in patients treated with azathioprine and cyclosporine.

Lymphocyte sensitivity to methylprednisolone (MP) was examined in 70 consecutive cadaver kidney recipients: 36 recipients were given prednisolone and azathioprine (Aza), while 34 patients received prednisolone and cyclosporine (CsA). Peripheral blood lymphocytes (PBL) isolated just before transplantation, and again 6-12 hr after transplantation and i.v. administration of 120 mg of MP were stimulated with phytohemagglutinin (PHA). The observation period for all recipients was six months. In vivo, administration of MP was followed by a significant (P less than 0.02) decrease in the mitogen response of lymphocyte cultures from Aza-treated patients with graft function (n = 23) at six months. In contrast, the mitogen response of lymphocyte cultures from patients with graft failure (n = 13) did not decrease. Lymphocyte cultures from CsA-treated patients with graft function (n = 26) were not more responsive to i.v. MP than cultures from recipients who lost their grafts (n = 8). In vitro, the dose-response curves to MP were examined in pretransplant PHA cultures. The lymphocyte cultures from Aza-treated patients with graft function were 20 times more sensitive to MP than those of patients with graft failure at six months. The difference was highly significant (P = 0.005). Lymphocyte cultures from CsA-treated patients who maintained graft function were 12 times more sensitive to MP than cultures from recipients who lost their grafts (P = 0.02). Thus, in vivo and in vitro lymphocyte sensitivity to MP, which can be examined before transplantation, is suggested to have an important influence on the graft survival of azathioprine-treated patients. Furthermore, this effect is partly modified by treatment with cyclosporine.

Adult↗
PubMed1987

Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes.

The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen-induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures decreased significantly after 48 h of stimulation with mitogen compared with that of 24 control cultures. The lymphocyte responses to phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) increased linearly with time, but the responses of the uraemic cell cultures were significantly lower than those of the control cultures. The relative numbers of cells double-stained for both Tac (IL-2 receptor)/HLA-DR or Tac/Leu 2 were significantly increased in the uraemic cultures as compared with the control cultures at 48 and 72 h. A similar, but not significant, trend was also demonstrated for uraemic cells positive for Tac/Leu 3. These findings were also seen in uraemic lymphocyte cultures supplemented with exogenous IL-2. Thus, the IL-2 production of uraemic lymphocytes seems to be exhausted more rapidly than that of normal lymphocytes, and there is no evidence that the poor proliferative response of uraemic lymphocytes is due to a decreased relative number of cells positive for IL-2 receptors.

Adult↗
PubMed1987

Lithium: long-term effects on the kidney. III. Prospective study.

Renal function in 32 patients treated with lithium for an average period of 10 years was reexamined 2 years after the first examination. A markedly influenced tubular function leading to increased urine volume (average 3 litres/24 h) and decreased renal concentrating capacity was still found, whereas glomerular function remained unimpaired in nearly all of the patients. No statistically significant changes in renal functions were observed at the follow-up examination. The results were compared with the same renal functional tests obtained from a control group consisting of 53 patients with affective disorders never treated with lithium. The control group had a significantly lower urine output (average 2 litres/24 h), but lithium-treated patients on a one-dose schedule had an average urine volume of only 500 ml/24 h more than the controls. In conclusion, this prospective study found no evidence of a progressive impairment of glomerular or tubular function in lithium-treated patients reexamined after 2 years. Patients with affective disorders never treated with lithium had normal renal concentrating capacity.

Adult↗
PubMed1987

Glucocorticoid levels and lymphocyte functions in kidney transplanted patients.

The in vitro lymphocyte response to mitogen stimulation and the in vitro lymphocyte sensitivity to glucocorticoid were examined in 72 kidney transplanted patients before and after administration of high or low doses of glucocorticoid. Administration of 10 mg of prednisone orally to 10 patients did not significantly change the mitogen responses or the lymphocyte sensitivity to methylprednisolone. Likewise, administration of 100-120 mg of methylprednisolone, intravenously to 62 patients did not significantly affect the mitogen responses, but, in contrast, the lymphocyte sensitivity to the immunosuppressive effect of methylprednisolone was clearly increased. This effect was highly significant in both cyclosporine A and azathioprine treated patients. These findings suggest that a change of the lymphocyte sensitivity to the immunosuppressive effect of methylprednisolone may occur after a high dose of glucocorticoid, anaesthesia and surgery, although no changes of the immunefunctions in vitro can be demonstrated by examining the mitogen response of the lymphocyte cultures. No relationship was found in the present study between the individual lymphocyte sensitivity to glucocorticoid and metabolic clearance rate.

Adult↗
PubMed1987

The sensitivity and specificity of Hippuran renography as a diagnostic investigation of renal transplant rejection.

Renography is a valuable investigation of a graft, as it can alert suspicions of rejection before it is clinically discernible. Renographic signs of rejection are delayed excretory phase and decreased Hippuran uptake in phase 1 and 2. A prospective trial was performed including 319 necrokidney transplanted patients. In 139 patients, acute rejection was diagnosed on clinical parameters. The material was divided into two groups: 1. Transplant patients suffering from acute tubulointerstitial nephropathy and having unmeasurably low creatinine clearance and an initial renogram showing an accumulation curve. 2. Patients with functioning grafts exposing a renogram with an excretion phase. The prevalence of rejection was 0.19 and 0.33, respectively, in the two groups. The sensitivity and specificity of renography as a parameter for diagnosing rejection was for group 1: Sensitivity 0.77 and specificity 0.95. Group 2: Sensitivity 0.68 and specificity 0.84. Efficiency of renography as a predictive test for the whole material was 74 percent. In group 1: 92 percent and in group 2: 79 percent. Acute rejection was diagnosed with renography in group 1 in 30/39 episodes before it was clinically evident. In group 2, with functioning grafts, rejection was diagnosed in 67 percent of the cases one to two days before it was clinically manifest. On the day of clinically manifest rejection, 92 percent of the renograms showed positive signs of rejection. False positive renographic signs of rejection were mainly caused by urinary tract obstruction, infection, and medication.

Acute Disease↗
PubMed1987

The influence of ischemia on 131I-Hippuran renograms performed after kidney transplantation and its prognostic value.

Within 72 hours after 289 uncomplicated cadaver kidney transplantations, 131I-ortho-iodo-hippurate renography was performed. The renographic changes caused by ischemic damage were correlated to the length of warm and cold ischemia times and followed during the recovery of graft function. Normal or slightly decreased phase 1 and 2 were seen in approximately 65 percent of the renograms if warm ischemia time was shorter than 15 min and the cold ischemic period less than 10 hours. For cold ischemia longer than 10 hours, the proportion was 30-60 percent. Warm ischemia time between 15 and 30 min caused a decrease of phase 1 and 2. Approximately 40 percent were normal or reduced if the cold ischemia time was less than 10 hours; for longer than 10 hours, the proportion was approximately 30 percent. Renograms with an excretion phase were mainly seen in the group with warm ischemia time less than 15 min combined with cold preservation for less than 20 hours. The phases of the post transplant renograms were closely correlated to the creatinine clearance. A normal or slightly decreased phase 1 or 2 was seen in patients with a clearance of 20-35 ml/min, moderately decreased phase was seen in the group with clearance of 10 ml/min, severely changed phase in the group with clearance of 0-5 ml/min. Correlating the onset of renal function to the initial posttransplant renogram showed immediate onset of function of 65 percent of the grafts with a normal or slightly decreased phase 1 or 2, as opposed to 15 percent of the grafts with moderately to severely decreased phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Recipient lymphocyte sensitivity to methylprednisolone affects cadaver kidney graft survival.

In 42 recipients of mixed-lymphocyte-culture (MLC) incompatible cadaver kidneys and conventional immunosuppressive treatment (azathioprine and steroids) the concentrations of methylprednisolone suppressing the in-vitro response of pretransplant lymphocytes to phytohaemagglutinin by 50% (ED50) were determined. 1-year graft survival was significantly higher in 21 recipients with methylprednisolone ED50 values below the median than in 21 patients with higher than median ED50s (86% v 29%; p less than 0.0002). Thus, the steroid sensitivity of recipients strongly influences the survival of MLC-mismatched kidneys. In 42 transplant recipients treated with cyclosporin and steroids, the effect of steroid sensitivity was also apparent (1-year graft survival 76% and 57% for recipients with low and high ED50, respectively), though not significant. Determination of the sensitivity to steroids may be valuable in determining which recipients can be given HLA-DR-mismatched kidneys and may serve as a guideline for determining the dose of steroids to be used.

Cadaver↗
PubMed1986

Lithium: long-term effects on the kidney. I. Renal function in retrospect.

46 patients treated with lithium for an average of 8 years participated in a functional-morphological follow-up study based on a 12-day hospitalization and involving a kidney biopsy. The functional part of the study showed that tubular function was markedly influenced, leading to increased urine volume (average 3 1/24 h) and a decreased renal concentration capacity in 85% of the patients. Glomerular function was generally not influenced, and only 10% of the patients had glomerular filtration rates below their age-corrected normal ranges. Both urine volume and glomerular filtration rates showed significant correlations with dosage schedule. Urine volume was lower and glomerular filtration rate higher on a one-dose schedule than when lithium was given in divided doses during the day. It is concluded that discontinuity in lithium treatment minimizes lithium effects on kidney function.

Adult↗
PubMed1986

beta-Blockade used in precision sports: effect on pistol shooting performance.

In a double-blind cross-over study of 33 marksmen (standard pistol, 25 m) the adrenergic beta 1-receptor blocker, metoprolol, was compared to placebo. Metoprolol obviously improved the pistol shooting performance compared with placebo. Shooting improved by 13.4% of possible improvement (i.e., 600 points minus actual points obtained) as an average (SE = 4%, 2P less than 0.002). The most skilled athletes demonstrated the clearest metoprolol improvement. We found no correlation between the shooting improvement and changes in the cardiovascular variables (i.e., changes of heart rate and systolic blood pressure) and no correlation to the estimated maximum O2 uptake. The shooting improvement is an effect of metoprolol on hand tremor. Emotional increase of heart rate and systolic blood pressure seem to be a beta 1-receptor phenomenon.

Adrenergic beta-Antagonists↗
PubMed1986

Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes.

The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte cultures. Furthermore, the increased uremic lymphocyte sensitivity to methylprednisolone was normalized by addition of IL-2 to the cultures. The measured IL-2 production had clearly decreased in the HD cultures after 48 h as compared to that of the control cultures. A similar but not significant trend was also seen in the CAPD cultures. Thus, it is suggested that a deficient production of IL-2 may partly explain the reduced lymphocyte response of uremic lymphocytes in vitro.

Adult↗