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Biomedical subjects

K O Pedersen

Publications and source records attributed to K O Pedersen.

At least 19 recordsLinked to original sources
PubMed1997

Metabolic cobalamin deficiency in patients with low to low-normal plasma cobalamins.

Over a 2-year period, we examined 48 patients with P-cobalamin levels in the difficult "grey zone" at the lower reference limit detected by a competitive protein binding assay using intrinsic factor as binder. In 21 of 30 patients (70%) with low P-cobalamins we could not establish the diagnosis of metabolic cobalamin deficiency, but 1 of 18 patients (6%) with low-normal P-cobalamin values was confirmed metabolically cobalamin-deficient. Half of these 30 patients with low P-cobalamins had neuropsychiatric disorders, but only one-third of the latter patients had metabolic cobalamin deficiency. Ten of the remaining 15 patients (67%) were characterized as non-deficient. In patients with low-normal P-cobalamin level, we found neuropsychiatric disorders in 5 of the 18 (28%), but none of these had metabolic cobalamin deficiency. We conclude that P-cobalamins below the reference interval combined with typical neuropsychiatric symptoms or findings are not diagnostic of cobalamin deficiency and that further analyses are necessary.

Adult↗
PubMed1992

[Determination of vitamin b12 deficiency].

Development of cobalamin deficiency in the tissues is considered to be a process which lasts for years. Macrocytic anaemia and/or neurological symptoms do not occur until late in this process. Serum cobalamins as the only parameter have proved less suitable for differentiation between healthy individuals with low serum cobalamin values and patients who require cobalamin for the remainder of their lives. The need for a better indicator for cobalamin deficiency has been emphasized. Recently developed methods of measurement have rendered determinations of serum methylmalonic acid possible. This value is raised in cases of cobalamin deficiency in the tissues. The serum methylmalonic values have proved both sensitive and specific to determine the extent to which genuine cobalamin deficiency is present or not and may also be employed for monitoring the effect of treatment as the raised values becomes normalized following substitution therapy with vitamin B12.

Humans↗
PubMed1992

[Laboratory diagnosis of cobalamin deficiency. A comparative study of 2 serum cobalamin methods and serum methylmalonic acid].

The diagnosis of cobalamin deficiency is established traditionally by demonstration of lowered serum cobalamin, but, for many reasons it cannot be anticipated that the concentrations of cobalamins in the serum reflect the relationship between blood cobalamin and tissue cobalamin accurately. The blood methylmalonic acid which cannot be metabolized in cases of cellular cobalamin deficiency should, on the other hand, indicate the cobalamin available for the tissues. A blind, prospective, controlled investigation was undertaken to compare the clinical employability of a recently developed method for measurement of the concentration of methylmalonic acid in the serum with older and more recent methods of measuring serum cobalamins. The three methods classified 94, 72 and 74% of the patients correctly, respectively (n = 50). The results reveal that serum methylmalonic acid is a more sensitive and specific analysis for demonstrating whether cobalamin deficiency was present or not. Serum cobalamins measured by both methods are relatively insensitive and unspecific markers for cobalamin deficiency in the tissue. Low cobalamin concentrations do not indicate that the patient in question has cobalamin deficiency, and values in the lower half of the reference interval do not exclude cobalamin deficiency. Measurement of methylmalonic acid in the serum is recommended in patients with low-normal or low serum cobalamin.

Adolescent↗
PubMed1992

[Cobalamin deficiency despite normal serum cobalamins].

In a man aged 77 years with normal concentrations of cobalamins in the serum, the concentration of methylmalonic acid in the serum was raised (2,920 nmol/l; 50-370 nmol/l). (The serum cobalamin concentrations were measured both by an old R-binder method (400 pmol/l; reference interval 200-800 pmol/l) and by a more recent S-binder method (164 pmol/l; 95-585 pmol/l)). Following a saturation dose of vitamin B12, the serum concentration of methylmalonic acid became normal (215 nmol/l) indicating that the patient had had functional cobalamin deficiency. The clinician should never let himself be deceived by a normal concentration of cobalamins in the serum and thus discard a suspicion of cobalamin deficiency. Measurement of serum methyl-malonic acid, which is a sensitive and specific analysis to differentiate between the presence or absence of cobalamin deficiency, is recommended to elucidate cases of doubt.

Aged↗
PubMed1991

[Costs and prices of laboratory services].

Cost accounting is performed in private and public laboratories. Guidelines for these activities are required and with this objective in mind, the Board of the Danish Society of Clinical Chemistry commissioned a working group to produce a position paper which is presented now in this report. The report discusses the objectives, the principles and the general requirements for cost accounting. The significance of information on costs for the clinicians' rational use of the laboratory is also illustrated. The working group points out that prerequisites for lucid and appropriate costing guidelines are clarification of which purposes information on costs are meant to serve, identification of the relevant cost centers and quality assurance of laboratory services to a defined extent. It is common practice to express laboratory costs as costs per test. The report advocates calculation of the cost per patient contact, i.e. the overall costs for laboratory service in a given investigative situation.

Accounting↗
PubMed1991

The prognostic value of estrogen and progesterone receptors in female breast cancer. A single center study.

In the period from September 1980 to December 1987, our laboratory measured estrogen (ER) and progesterone receptor (PgR) levels in 960 patients with primary breast cancer. At presentation, 918 of these had no distant metastases. ER as well as PgR were considered positive at values above 10 fmol/mg cytosol protein. All the patients included had been operated on at one of two participating hospitals in the country of North Jutland, and all patients had been checked up in a uniform way at one oncological out-patient department. By applying test for interaction, the PgR was found to be dependent on nodal status. Separate multivariate analyses were carried out for node positive and node negative patients. By this method, size of tumor, histologic grading, and age turned out to be independent prognostic factors for the node negative patients. Independent prognostic parameters for the node positive patients were histologic grading, PgR and postoperative x-ray therapy. The results support the theory that PgR is a better predictor of disease-free survival than ER.

Breast Neoplasms↗
PubMed1990

The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid.

Over a 1-year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S-protein binder, RIA). In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non-cobalamin deficient. The serum methylmalonic acid level was higher than 0.34 mumol l-1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin-deficient subjects, and below this level in 10 of the 11 non-deficient patients. We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non-cobalamin deficiency (efficiency = 0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency.

Adult↗
PubMed1990

Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism.

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 age- and sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.

Adult↗
PubMed1989

Estrogen receptor analyses in breast cancer: comparison of monoclonal immunohistochemical and biochemical methods.

The estrogen receptor content in 100 female breast carcinomas was determined using the biochemical dextran-coated charcoal (DCC) method and the monoclonal estrogen receptor immunocytochemical assay (ER-ICA). Great care was taken to make procedures optimal in order to minimize preanalytical errors. A statistically highly significant correlation was found between the results of the two methods, which were qualitatively in accordance in 91 cases, while nine gave a negative ER-ICA but a weak positive DCC result. The quantitative correlations were also statistically significant but varied considerably in individual cases. Under optimal conditions, ER-ICA provides results similar to the DCC method, but it is still uncertain if it can stand alone in routine diagnosis.

Antibodies, Monoclonal↗
PubMed1988

Impact of standardization of estrogen and progesterone receptor assays of breast cancer biopsies in Denmark.

Estrogen and progesterone receptor (ER and PgR, respectively) data for the three laboratories participating in the Danish Breast Cancer Cooperative Group (DBCG) project for treatment of primary breast cancer are presented for the period 1979-1986. The frequency of ER positivity remained constant for one laboratory throughout this period, while this value changed significantly in the other two laboratories. Inter-laboratory reproducibility (evaluated as the frequency of ER positivity) was poor at the onset of the project (P = 0.0003) but, due to standardization procedures, improved after 1982. Slight but significant differences in the composition of the patient populations at the three centers (menopausal status and tumor size) may account for some of the differences observed both in frequency of PgR positivity as well as PgR concentrations determined. Greater intra- and inter-laboratory differences were observed in all three laboratories for PgR than for ER. Part of this variation is believed to have been alleviated by the addition of 10 mM sodium molybdate to the assay buffer in 1983. From having very divergent frequencies of PgR positivity in the three laboratories (31-71%) in 1981, this divergence has been reduced in 1985 (62-78%). While data regarding ER status significantly distinguish between patients with long versus short recurrence-free survival (irrespective of treatment) in one laboratory in both the 77 and the 82 generations of clinical protocols within the DBCG program, ER status from the other two laboratories makes this distinction only in the 82 protocols. We attribute this inability of ER status to distinguish among patients in the 77 protocols to the suboptimal nature of the assays performed in these two laboratories at that time. The overall improvement in comparability of data from the three laboratories during the standardization procedures as well as the fact that ER status from all three laboratories is now capable of distinguishing different patient groups attest to the fact that standardization procedures are both necessary and useful.

Aged↗
PubMed1988

Quality control of receptor analyses of breast cancer tissue in Denmark.

Quality control investigations of estrogen and progesterone receptor (ER and PgR respectively) analyses can be undertaken using two principally different methods. The first, and the most frequently employed, is by comparing the results of analyses of a lyophilized, standard cytosol. The second method is by comparing the frequency of receptor positivity as well as the distribution of the receptor concentrations determined on a large number of representative biopsies in different laboratories. This latter method can, however, only be used provided that the composition of the population of biopsies studied is similar in the laboratories undertaking such an investigation. Both approaches have been used by the three Danish laboratories participating in the Danish Breast Cancer Cooperative Group (DBCG) project. The international and national quality control programs that these three laboratories have participated in are reviewed in the present paper. From having a poor degree of inter-laboratory reproducibility in 1981, the inter-laboratory reproducibility has improved due to a collaborative standardization effort. Using the clinical data available through the DBCG program, we have been able to demonstrate that suboptimally performed receptor analyses can influence the conclusions of clinical studies regarding patient prognosis in relation to receptor status.

Aged↗
PubMed1986

Renal tubular reabsorption of calcium in familial hypocalciuric hypercalcaemia.

To investigate the nephron site of the enhanced tubular calcium reabsorption in familial hypocalciuric hypercalcaemia (FHH), the renal plasma clearance of lithium and calcium and the glomerular filtration rate were determined simultaneously after an overnight fast in nine FHH patients and ten healthy controls. As the renal plasma clearance of lithium equals the rate of the proximal tubular fluid delivered into the thin descending loop of Henle's loop, the reabsorption of calcium in the proximal and distal tubule, respectively, could be calculated. We found that the FHH patients had a significantly higher fractional calcium reabsorption in the proximal tubule (77.6 +/- 4.7 (%) vs 73.3 +/- 3.1, P less than 0.05). The same held true for the absolute proximal calcium reabsorption (1.49 +/- 0.12 (mmol/l) vs 1.07 +/- 0.05, P less than 0.001). There was a significant linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption (r = 0.70, P less than 0.05). The distal tubular calcium reabsorption did not differ in the two groups. Our results therefore suggest that the enhanced tubular calcium reabsorption in FHH takes place exclusively in the proximal renal tubule.

Adolescent↗
PubMed1985

Comparison of histo- and biochemical methods for estrogen and progesterone receptor analysis in primary human breast carcinoma.

One hundred and twenty-three primary breast carcinomas have been examined under optimal procedural conditions for presence and quantity of estrogen (ER) and progesterone (PgR) receptors by a histochemical method using hormones conjugated to fluoresceinated bovine serum albumin and by a conventional biochemical (dextran-coated charcoal) assay. The semiquantitative histochemical results for ER and PgR were strongly positively correlated, as were the corresponding quantitative biochemical results, but there was no significant correlation between histo- and biochemical results for ER, nor between the corresponding results for PgR. By generally accepted cut-off limits for positivity there was an equal frequency of ER- and PgR-positive tumors by the histochemical method (71 and 67% respectively), whereas there was a significantly higher frequency of ER- than PgR-positive tumors by the biochemical method (76 and 59%). The qualitative agreement between the two methods was 76% for ER and 61% for PgR, and there was a correspondingly inferior sensitivity and specificity of the histochemical method in comparison with the biochemical method, whose value is clinically validated.

Breast Neoplasms↗
PubMed1985

Familial hypocalciuric hypercalcaemia I: Renal handling of calcium, magnesium and phosphate.

Ten hypercalcaemic members from three generations of a family with familial hypocalciuric hypercalcaemia (FHH) were compared with age and sex matched healthy subjects. Two of the former had undergone unsuccessful subtotal parathyroidectomy. Our results showed that the hypercalcaemia was mainly attributable to an increased capacity for tubular reabsorption of calcium, but in part also to an increased release of calcium from bone. The relative hypermagnesaemia had a similar dual origin. The serum phosphate concentration was low and this could be accounted for in full by a decrease in renal tubular reabsorption of phosphate, as assessed by the renal threshold phosphate concentration (TmPO4/GFR). The results of PHT measurements with two radioimmunoassays were equivocal. Most patients had normal serum PTH values, but with one assay mean serum PTH was significantly higher in the hypercalcaemic group. We conclude that the abnormalities of the divalent cation and phosphate metabolism cannot be accounted for in full by increased circulating PTH activity, and are predominantly due to an intrinsic renal abnormality.

Absorption↗