PubMed Health⌕ Search

Biomedical subjects

S Ladefoged

Publications and source records attributed to S Ladefoged.

10 recordsLinked to original sources

Optimizing lithium dosing in hemodialysis.

We studied a 62-year-old female hemodialysis patient during initiation and maintenance of lithium carbonate therapy. Three different methods were applied to estimate the regimen: a scenario based on volume of distribution (V(d)), a scenario based on glomerular filtration rate (GFR), and a scenario in which we developed an algorithm based on a 2-compartment distribution without elimination. The GFR estimate led to plasma concentrations 3-4 times lower than those anticipated. In contrast, the estimates based on V(d) and the algorithm derived from pharmacokinetic modeling led to comparable loading dose estimates. Furthermore, the maintenance dose estimated from the central compartment (V1) led to plasma concentrations within the therapeutic range. Thus, a regimen where 12.2 mmol lithium was given after each hemodialysis session resulted in stable between-dialysis plasma lithium concentrations in this patient with no residual kidney function. We did not observe adverse effects related to this regimen, which was monitored from 18 days to 8 months of therapy, and the patient experienced relief from her severe depressive disorder. In conclusion, dialysis patients may be treated with lithium administrated immediately postdialysis. Further observations are necessary to obtain robust long-term safety data and to optimize the monitoring schedule.

Aged↗

The effect of recombinant human growth hormone treatment on bone and mineral metabolism in haemodialysis patients.

BACKGROUND: Uraemia and chronical haemodialysis are associated with an abnormal growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to malnutrition and renal bone disease. Short-term studies have shown a beneficial effect of treatment with recombinant human growth hormone (rhGH) on nutritional status in patients on haemodialysis. In the present study, we evaluated the effect of rhGH on bone and mineral metabolism. METHODS: Twenty chronic malnourished patients on haemodialysis took part in a double-blind, placebo controlled trial with subcutaneous injections of rhGH (4 IU/m2/day) or placebo for 6 months. RESULTS: During rhGH treatment, serum IGF-1 increased 264 +/- 52% (mean +/- SEM) (P < 0.008). There were no significant changes in biochemical markers of mineral metabolism (serum ionized calcium, phosphate and parathyroid hormone). Among markers of bone metabolism, there was a significant increase in serum procollagen type I C-terminal propeptide (maximum 155 +/- 8%, P < 0.001) and no significant changes in serum alkaline phosphatase. Bone densitometry showed a significant decrease in whole body bone mineral content (95.7 +/- 1.2%) after 6 months treatment. The effects on the proximal femur were not significant. CONCLUSION: The effects of 6 months treatment with rhGH seen in this study are best explained by a GH- or IGF-1-induced increased bone turnover. Long-term treatment in larger cohorts followed by bone densitometry and, preferentially, bone histomorphometry are needed to evaluate whether this is a beneficial effect in haemodialysis patients.

Adolescent↗

Selection of Mycoplasma hominis PG21 deletion mutants by cultivation in the presence of monoclonal antibody 552.

Three mutants of Mycoplasma hominis PG21 were isolated and shown to contain alterations in the size of a repeat-containing gene encoding a surface-localized 135-kDa antigen designated Lmp1. The mutants were isolated by cultivating M. hominis for a 3-month period in the presence of Lmp1-specific monoclonal antibody (MAb) 552. The epitope for MAb 552 was localized at the repeated part of the protein. The gene encoding Lmp1 is part of a transcriptional complex that contains 9.5 direct repeats of 471 bp each. Pure cultures of mutant strains were obtained by subcloning, and three mutants were characterized. The mutants showed deletions of a various number of repeats. The deletions were accompanied by a decrease in size of the proteins. With increasing size of deletions, agglutination and growth inhibition by MAb 552 became less pronounced. Spontaneous aggregation of the mutant M. hominis cells in culture medium was, however, increased, indicating that the repeated elements may be of importance for repulsion of the cells.

Agglutination Tests↗

Polymerase chain reaction as a rapid diagnostic assay for cytomegalovirus infection in renal transplant patients.

The aim of this study was to apply a polymerase chain reaction for diagnosis of CMV infection and determine its clinical value in renal transplant recipients. We have applied the PCR to urine and blood specimens collected from 27 renal transplant recipients as well as blood from 49 normal blood donors. Ten of twenty-seven patients, compared to 3 of 49 normal blood donors, had CMV-DNA present in one or more samples. Six of the ten CMV-DNA-positive patients had positive CMV serology, and 3 of the 10 had severe clinical symptoms of active CMV infection. In four additional patients with positive CMV serology - but without clinical signs of active CMV infection - no CMV-DNA could be detected by the PCR. In the three patients with severe symptoms, PCR could detect CMV-DNA before serology became positive, and in one of these three patients, serology remained negative despite the patient's death from clinically obvious CMV pneumonia. PCR thus appears capable of detecting active CMV infection at a time when CMV serology is inconclusive, but cannot substitute for serology as the only routine analysis since a transient viraemia might be missed. However, in immunosuppressed patients with severe CMV infection, PCR could provide an early diagnosis, enabling the clinician to implement early specific treatment.

Antibodies, Viral↗

Expression of the intercellular adhesion molecule-1 (ICAM-1) in human renal allografts and cultured human tubular cells.

The in vivo distribution of the intercellular adhesion molecule ICAM-1 was investigated in renal tissue specimens obtained from 17 renal allotransplanted patients, nine normal kidneys (controls), seven native kidneys, nine patients with mesangioproliferative glomerulonephritis, and nine patients with active extracapillary glomerulonephritis. Biopsies from patients with signs of acute rejection showed a significant increase in ICAM-1 expression in the tubular epithelium (P less than 0.05). In normal kidneys (controls) ICAM-1 expression was found in endothelial cells; additional expression in the tubular epithelial cells was induced in patients with extracapillary glomerulonephritis. The in vitro expression of ICAM-1 was examined in cultured human tubular cells after stimulation with gamma-interferon and interleukin-1, treatment with cyclosporin and/or verapamil and coculture with allogenic mononuclear cells. An increased ICAM-1 expression was demonstrated by coculture with allogenic mononuclear cells and after stimulation with gamma-interferon and/or interleukin-1. Cyclosporin or verapamil induced no changes. Our results give support to the hypothesis that ICAM-1 upregulation is important in immune interactions such as allograft rejection. Furthermore, the in vitro model indicates that ICAM-1 expression is regulated by gamma-interferon and interleukin-1 produced by activated T lymphocytes and macrophages.

Adult↗

Lack of effect of intravenous LHRH on plasma noradrenaline in man.

One hundred microgram of LHRH was given intravenously to two male and two female subjects. Plasma noradrenaline did not change following LHRH, in contrast to findings reported by others. There was no change in heart rate and systolic arterial blood pressure. LH increased significantly as expected.

Adult↗

Assessment of verapamil in the treatment of angina pectoris.

A brief review is given of the pharmacological data of verapamil, which chemically shows a certain similarity to papaverine. The effect of the drug (80 mg) 3 times daily, on angina pectoris, as compared with placebo, was evaluated in a double-blind cross-over therapeutic trial with 4-wk periods in 47 patients. The incidence of attacks and the nitroglycerine consumption decreased in the second fortnight of the verapamil period by approximately 25% compared with the placebo period. An ergometer test showed a prolongation of the exerice time of 20%. The mean blood pressure and the heart rate fell under verapamil treatment if the patients had values which were relatively high in the placebo period. The increase in heart rate during exercise from two different resting levels showed a tendency to become more pronounced under treatment with verapamil than under placebo. The length of the P-Q intervals were not affected by verapamil. The mechanism of action in angina pectoris is discussed, but it is concluded that it is still not possible to explain it. Twelve Danish medical departments took part in the trial.

Aged↗