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Biomedical subjects

L Theodorsen

Publications and source records attributed to L Theodorsen.

At least 19 recordsLinked to original sources

Experiences of the Janus Serum Bank in Norway.

The ongoing JANUS project was started in 1973. The serum bank comprises 424,938 serum samples consolidated from 293,692 donors. The specimens are stored at -25 degrees C. From 1 to 13 consecutive samples are available from each donor. Up to October 1993 about 14,000 of the donors had developed some form of cancer. Frozen serum samples collected from a few months to 19 years prior to clinical recognition of their disease are available for research purposes. The principle aim of the JANUS project is to search in the premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA-125 may be elevated months prior to the diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumor marker in subgroups of thyroid cancer; low levels of selenium in serum reflects increased risk of thyroid cancer; raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkins disease; prostate-specific antigen may be elevated years prior to clinical diagnosis of prostate cancer; and linoleic acid in serum phospholipids is inversely related to breast cancer risk. The serum bank is, in principle, suitable for environmental studies, e.g., human exposure assessment. The steering committee of the JANUS project is open to suggestions for collaborative research on this topic.

Biomarkers, Tumor

[Tumor marker analyses--valuable tools if used correctly].

The tumour marker assays in routine use today are not cancer-specific. Most markers are normal products of epithelial tissues, usually excreted from the intact organ. The infiltrating malignant growth allows release directly into lymph and blood, where the product is measured as a "tumour marker". Many tumour markers are glycoproteins depending on the liver function for their catabolism. These mechanisms explain the slight to moderate increases in tumour marker values found in various non-malignant diseases. Therefore, in general, such assays are of no use for screening healthy populations, and a normal value does not exclude cancer. Their main use is in the primary staging of patients known to have cancer, to evaluate the completeness of primary surgery, to follow-up patients for early detection of relapses, and to monitor the effect of cytotoxic or radiation therapy of advanced disease. In all these applications, good clinical judgement is the necessary basis for using these assays.

Biomarkers, Tumor

Safety and tolerability of iodixanol in healthy volunteers with reference to two monomeric X-ray contrast media.

The low osmolar, non-ionic X-ray contrast media have shown a lower frequency of adverse events than the older ionic ones. In this study changes in routine clinical-chemical parameters in blood and urine, vital signs and adverse events were recorded in six groups of 10 healthy male volunteers receiving either iodixanol, a new non-ionic, dimeric X-ray contrast medium for general vascular use, or one of the two non-ionic, monomeric contrast media iopentol and iopamidol. Minor decreases were observed in the values for haemoglobin, haematocrit and erythrocytes 5 min and 3 days after injection of iodixanol. A minor increase was seen in platelets and total protein after 3 days. A transient increase in serum osmolality was seen 5 min after the injections of iopentol and iopamidol. This was not seen in any iodixanol group. The level of thyrotropin showed an increase in all groups at 3 days. It was back to normal within 21 days. No changes of clinical importance were seen regarding blood pressure, heart rate or ECG in any volunteer. No severe adverse events were reported. All events were of short duration, and of mild or moderate intensity. The results, however, may indicate a lower frequency of adverse events/discomfort after the administration of the dimeric iodixanol than the 2 monomeric contrast media iopentol and iopamidol.

Adult

Prediction of long-term gonadal toxicity after standard treatment for testicular cancer.

Long-term post-treatment gonadal toxicity was examined (median 3 years after treatment discontinuation) in 125 testicular cancer patients treated with standard regimens: no radiotherapy or chemotherapy (36 patients), infradiaphragmatic radiotherapy (38 patients), and 3-4 cycles of cisplatin-based chemotherapy (51 patients). Radiotherapy and chemotherapy had no impact on serum testosterone, but led to a slight increase in serum follicle-stimulating hormone (FSH). The lowest median value of post-treatment sperm cell count was observed after infradiaphragmatic radiotherapy, the highest value after standard chemotherapy. After more intensive cytotoxic treatment recovery of the gonadal function seemed to be delayed. In testicular cancer long-term post-treatment gonadal toxicity is correlated to the patient's pretreatment gonadal function and age rather than to the standard treatment of the malignancy. In patients with pretreatment normal gonadal function the risk of permanent treatment-induced toxicity is minimal after present standard treatment.

Adolescent

Glomerular filtration rate, 131I-hippuran clearance and estimated creatinine clearance in cancer patients.

Glomerular filtration rate (GFR), 131I-Hippuran clearance and estimated creatinine clearance were investigated in 34 patients with cancer. For Hippuran clearance and GFR, analysed with the X-ray contrast (iohexol) and fluorescence technique, the least square linear regression coefficient was 5.01 +/- 0.41 (r = 0.91). This value concurs with the five to one ratio between GFR and renal plasma flow known from normal physiology and supports that Hippuran clearance is a valid measure of renal function. When the individual values of Hippuran clearance were divided by 5.01, the mean difference between the methods was 0.4 ml min-1 1.73 m-2 with standard deviation 13.4 ml min-1 1.73 m-2. The lower and upper limits of agreement were -26.7 and 25.9 ml min-1 1.73 m-2, respectively. Comparing creatinine clearance estimated from the serum creatinine level with GFR, the limits of agreement were -29.4 and 21.6 ml min-1 1.73 m-2. These agreement limits are in the same range as those which can be calculated from the data from other studies.

Creatinine

DNA flow cytometry in sperm cells from testicular cancer patients. Impact of different treatment modalities on spermatogenesis.

In 77 patients with testicular cancer, sperm cell density was evaluated before and after treatment together with the following parameters as recorded by DNA flow cytometry: the percentage of condensed and non-condensed haploid sperm cells, and the number of non-haploid cells. The patients received either abdominal radiotherapy, cisplatin-based combination chemotherapy (+/- surgery) or did not undergo antiproliferative treatment at all. Ejaculates with a low sperm cell density had high numbers of non-condensed haploid and non-haploid cells, whereas the percentage of condensed haploid cells was decreased. However, even 'azoospermic' semen samples (by light microscopy) contained haploid cells indicating ongoing sperm cell production. One year after radiotherapy there was a significant decrease in the sperm cell density and the number of condensed haploid cells. Chemotherapy led to a significant reduction of sperm cell density evaluated 1 year after treatment. Three years after the diagnosis of testicular cancer, sperm cell production had recovered in most patients. In patients who did not have radiotherapy or chemotherapy the median density of sperm cells 3 years after treatment significantly exceeded the corresponding figure from the pretreatment situation. A low pretreatment percentage of condensed haploid cells (less than or equal to 90%) was correlated with the lack of 1-year recovery of sperm cell production. It is too early to state whether longitudinal flow cytometric data from ejaculates in testicular cancer patients yield clinically valuable information, in addition to that obtained by light microscopy. From this preliminary observation it seems that DNA flow cytometry in ejaculates from testicular cancer patients may give valuable clinical information about sperm cell production following treatment.

Antineoplastic Agents

Recovery of impaired pretreatment spermatogenesis in testicular cancer.

Light microscopic sperm analysis was done 24 months after treatment or later in 25 patients with testicular cancer with azoospermia or severe oligospermia (sperm cell count less than 10 x 10(6)/mL) after orchiectomy before further treatment. Treatment after orchiectomy consisted of abdominal irradiation, cisplatin-based chemotherapy, retroperitoneal surgery, a combination of the former treatment modalities, or a surveillance policy. At the time of post-treatment reassessment, 15 of the 25 patients had sperm cell concentrations of at least 10 x 10(6)/ml (7 of 14 patients in the azoospermia group; 8 of 11 patients in the oligospermia group). Eight patients fathered a child after discontinuation of treatment for testicular cancer. Recovery of spermatogenesis could be seen after all types of treatment. A highly increased pretreatment serum follicle-stimulating hormone was correlated with lack of sperm cell production recovery.

Adult

Automated cyanide-free method for haemoglobin determination on Technicon H.1.

We have developed a cyanide-free haemoglobin method for our Technicon H.1 counter. By adding 2.5 mmol/l of the ionic surfactant sodium dodecyl sulphate in 154 mmol/l sodium chloride, the haemoglobins are converted to a stable product, denatured globin haemichrome, within the 25 s available on the instrument. The method is as precise and accurate as the original H.1 method, and the reagent is easily made in the laboratory at a very low price. Since the method is relatively safe with regard to waste disposal, the effluent from the counter can be drained into the laboratory sink. The method, a 'SDS-haemichrome method', has now worked very satisfactorily in routine use for a year. Manufacturers of haematological analysers should consider this haemoglobin method for their automated instruments.

Autoanalysis

Alterations of blood analyses at relapse of osteosarcoma and Ewing's sarcoma.

Alterations of blood analyses have been studied at relapse of patients with osteosarcoma and Ewing's sarcoma. The tests included erythrocyte sedimentation rate (ESR), haemoglobin (Hb), leukocyte and thrombocyte counts, gamma glutamyltransferase (GT), lactate dehydrogenase (LD) and alkaline phosphatase (ALP). Sixteen relapsing patients diagnosed from 1970 to 1987 were eligible in each sarcoma group. Median age was 16 years (range 9-30) at diagnosis. The blood tests seemed to be of no help in detecting relapse of osteosarcoma, while ESR, LD and GT rose significantly in relapsing patients with Ewing's sarcoma. ESR was best correlated to disease activity.

Adolescent

DNA flow cytometry in sperm cells from unilaterally orchiectomized patients with testicular cancer before further treatment.

Light microscopic sperm cell analysis and DNA flow cytometry in the seminal fluid were done in 85 testicular cancer patients after orchiectomy before further treatment. The results were compared with those from 26 healthy age-matched males (control group). A computer-based method for analysis of the DNA histograms was developed for evaluation of the percentage of sperm cells within the sub-haploid, haploid (1c), and diploid (2c) and greater than 2c levels. Compared with the control group, testicular cancer patients had a reduced sperm cell density and sperm cell motility. The mobility grade was also significantly reduced as compared with healthy males. In addition, the number of condensed haploid sperm cells (within the subhaploid level) was decreased in testicular cancer patients, whereas the percentages of noncondensed haploid (1c), diploid, and greater than 2c cells were increased. Most of the DNA flow cytometric parameters were significantly correlated with sperm cell density. DNA flow cytometry in human seminal fluid offers a possible means of assessing spermatogenesis, thus providing an objective method for studying fertility disturbances, for example, in cancer patients before and after treatment.

Adolescent

Prediagnostic serum selenium in a case-control study of thyroid cancer.

Sera from 43 persons who developed thyroid cancer on an average 4.8 years after blood sampling were compared with sera from controls. Three controls per case matched for sex, age, place of residence and year of blood sampling, with regard to serum selenium and serum copper. Cases were significantly lower in serum selenium than controls, and the estimated odds ratio of thyroid cancer increased from 1 for levels greater than or equal to 1.65 mumol/l, to 6.1 for levels 1.26-1.64 mumol/l, to 7.7 for levels less than or equal to 1.25 mumol/l. When time from blood sampling to diagnosis of the case was considered, it could be shown that the protective effect of high serum selenium concentrations was restricted to the last (less than 7) years prior to the diagnosis of thyroid cancer. The serum selenium concentration of cases tended to decrease relative to controls the shorter time was from blood sampling to the diagnosis. There was no difference between cases and controls with regard to serum copper.

Adenocarcinoma

Haemoglobinometry on automated haematology analysers.

It is generally recognized that the standardized cyanmethaemoglobin (HiCN) method is the preferred method for the determination of haemoglobin in blood. In automated analysers, however, the reaction time available before the photometric measurement is too short. With the Ortho ELT800 we found that the conversion into HiCN took longer than 25 s. More important was the variation of results with the haemoglobin derivatives present in the blood sample. Our experiments suggest that Coulter counters and other automated analysers as well use denaturated globin haemichrome as the end product in their haemoglobin procedure although they profess to use HiCN by the addition of cyanide to the reagents. However, haemichrome is a suitable alternative for automated analysers as the conversion time is very short for all haemoglobin derivatives including HbCO. In the Coulter S Plus III where white cell size distribution analysis and haemoglobin determination are performed in the same solution, the haemoglobin derivative formed shortly after mixing is not a stable one. White cell size analysis and haemoglobin determination should preferably be performed in separate channels with different lysing reagents giving optimal conditions for each determination. Evaluation of the analysers would be easier if the manufacturers would give correct information on the chemistry of the haemoglobin method and state the composition of the reagents used.

Hemoglobinometry

Diagnostic efficiency of biological markers in blood serum on prostate cancer: a comparison of four different markers and 12 different methods.

Serum-acid phosphatase as measured by nine different methods, serum prostate-specific antigen, cancer antigen CA-50, and creatine kinase BB isoenzyme have been evaluated and compared with respect to efficiency in differentiating between prostate cancer and benign hyperplasia. The patient material consisted of 92 prostate cancer patients (59 untreated, and 33 previously treated), 106 patients with benign hyperplasia and 66 patients with non-prostatic urological diseases. The cancer group was classified according to the TNM-system, and also graded according to histopathological findings. The following main conclusions were drawn. Acid phosphatase activity, when measured with continuous monitoring procedure (substrate: alpha-naphthyl phosphate), showed on the average slightly, but statistically not significant higher diagnostic efficiency than when measured with conventional two-point discontinuous monitoring method (substrate: p-nitrophenyl phosphate). There was no or only marginal differences in diagnostic efficiency between activity measurements of the total acid phosphatase and the tartrate-labile fraction, and also between activity measurements and immunological measurements (PAP-RIA and PAP-IEA). Prostate-specific antigen was found to have statistically significant higher diagnostic efficiency than acid phosphatase, the former being positive in 17 of 25 patients with prostate cancer without distant metastases, and in six of 11 patients classified as T0-2 M0. Cancer antigen CA-50 and creatine kinase BB isoenzyme appeared to be of little diagnostic value. From a cost-effective point of view, total or tartrate-labile prostatic acid phosphatase activity, as measured by continuous monitoring technique with alpha-naphthyl phosphate as substrate, is suggested suitable as a first-choice parameter both for diagnostic and monitoring purposes with respect to prostate disease. Prostate-specific antigen may give additional information, and should be considered analysed on special request.

Acid Phosphatase

SCE Nordic alpha-amylase study. II: Assessment of proposed calibration procedure. A report by the Scandinavian Committee on Enzymes (SCE).

Eighty-seven Nordic Hospital laboratories participated in a joint SCE-NORDKEM follow-up study of the long-term stability of the previously established calibration factors for a number of alpha-amylase routine methods based on six different substrates. Human control materials with 90% pancreatic, 90% salivary, and pure pancreatic alpha-amylases were measured by the participants. The data were plotted before and after calibration of each method using a human pancreatic calibrator with an assigned catalytic concentration of 390 U/l (Phadebas blue starch method, 37 degrees C). As in the previous study, carried out 9 months earlier, the pre-calibration values varied over a six-fold range. The post-calibration values of all methods except those based on a tetraose substrate showed an acceptable inter-laboratory comparability. As a temporary measure, SCE recommends that the Nordic laboratories calibrate the accepted routine methods by their individual calibration factor. Detailed suggestions for calibration procedures and a discussion of the principles of transferability will shortly be published by the SCE in this journal.

Calibration

SCE Nordic alpha-amylase method selection and calibration study. A report by the Committee of Enzymes of the Scandinavian Society for Clinical Chemistry (SCE).

Seventy-six Nordic routine laboratories participated in a joint SCE-NORDKEM study comprising evaluation, selection, and temporary calibration of amylase methods. Human control materials with known fractions of salivary and pancreatic amylase were determined by seven routine amylase assays based on substrates with glucosyl (G) chain lengths G4, G5, G5-6, G7, G9, amylopectin and blue starch polymer (Phadebas). The data were plotted before and after calibration of each method using a human pancreatic calibrator with an assigned value of 390 U/l (37 degrees C, Phadebas). the study led to three conclusions: The analytical overestimation of salivary to pancreatic amylase ratio (S:P) increased with decreasing number of glucosyl units in the substrates. Relative to the S:P value of blue starch polymer (set at 1.00), for example, tetraose mean S:P value was 1.55. The hydrolysis rates relative to that with blue starch polymer decreased with the number of glucosyl units in the substrates. The precalibration values of all methods spread over an approximately six-fold range. Post-calibration values of all methods, except tetraose, showed an acceptable inter-laboratory comparability. The CV values for low, medium, and high controls were about 5.5, and 6% respectively. As a temporary solution to the current problem of diverse amylase assays, the SCE suggests calibration of the methods considered acceptable in this study. The long-term effects will be evaluated in a follow-up study within a year.

Calibration