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Biomedical subjects

K Liewendahl

Publications and source records attributed to K Liewendahl.

At least 55 records · Page 3Linked to original sources

Anti-melanoma antibodies bind preferentially to diploid metastases in immunoscintigraphy.

Immunoscintigraphy with 99Tcm-labelled anti-melanoma monoclonal antibody F(ab')2- fragments was performed in 23 patients with histologically verified metastatic melanoma. Immunoscintigraphy was positive in 14 patients and all known metastases were detected in eight patients, five of whom had only one lesion. Lesion localization and detectability were as follows: 12/13 (92%) cutaneous and subcutaneous, 11/14 (79%) lymph node, 5/7 (71%) bone, 3/6 (50%) lung and 1/5 (20%) abdominal metastases were visualized. Despite its high specificity--no false positive immunoscintigrams--the low sensitivity of this method in detecting deep metastases hampers its usability. The false negative results were not due to lack of antigen expression as positive immunostaining results were observed also in specimens from patients with negative immunoscintigrams. Flow cytometric analysis of the metastases revealed that in 7/8 (88%) patients with diploid tumours had positive immunoscintigrams but only 7/15 (47%) patients with aneuploid tumours. These results show that the diagnostic accuracy of melanoma immunoscintigraphy can be improved by selecting patients not only by testing for the antigen but also on the basis of DNA analysis of an accessible lesion.

Abdominal Neoplasms↗

Prostate tumour markers as an aid in the staging of prostatic cancer.

Serum acid phosphatase activity (ACP), prostate specific phosphatase (PAP) and prostate specific antigen (PSA) were measured in 100 patients with prostatic cancer. The patients were divided into 4 groups: T1-2 MO, T3-4 MO and M1 patients with less than or equal to 10 or greater than 10 metastatic foci in bone scintigraphy. The mean serum ACP levels were almost identical in the T1-2 MO and T3-4 MO groups and there was no significant difference between the mean PAP values. Significantly higher PSA levels were observed in the MO patients in the extracapsular category compared with those in the intracapsular category. The mean serum levels of all 3 tumour markers were significantly higher in the M1 than in the MO category. PSA seems to be the marker of choice as a diagnostic aid for differentiating between patients with intracapsular and those with extracapsular tumour growth. In prostatic cancer patients with bone metastases these markers were of similar value for staging the disease.

Acid Phosphatase↗

The development of nuclear medicine imaging.

Great progress has been made in nuclear medicine imaging during the forty years this imaging modality has existed. Advances have been made both in the area of instrumentation and radiopharmaceuticals. The development started with a single detector system but now imaging devices can produce tomograms displayed three-dimensionally on graphic monitors. The general trend in the production of radiopharmaceuticals has been the development of highly specific compounds for mapping of biological structures and functions.

Gamma Cameras↗

Compartmental analysis of short-lived platelet dynamics.

111In-labelled platelets were used for analysing platelet dynamics in 43 patients with idiopathic thrombocytopenic purpura (ITP). The detected time-activity curves, recorded with a gamma camera, were analysed by three methods: two- and three-compartment models, and an open model in which only the splenic curve was analysed. In the two-compartment model the mean rate constant from blood to spleen was 0.328 +/- 0.028 min-1 (mean +/- SEM) and from spleen to blood 0.061 +/- 0.007 min-1, whereas in the three-compartment model the corresponding values were 0.236 +/- 0.020 and 0.044 +/- 0.007 min-1, respectively. The mean rate constant from blood to liver was 0.466 +/- 0.149 min-1 and from liver to blood 0.341 +/- 0.106 min-1 as derived from the three-compartment model. The rate constant from spleen to blood, as determined from the three-compartment model, was significantly higher in patients with a strongly positive result for platelet-associated auto-antibodies (platelet suspension immunofluorescence test (PSIFT] than in patients with a negative PSIFT. The mean hepatic net rate in patients with a high level of antibodies is into the liver, while in patients with little or no antibodies the net rate is into the blood pool. The mean half-life for the fast component of the inverted splenic curve was 2.5 +/- 0.2 min and for the slow component 16 +/- 2 min. In patients with a strongly positive PSIFT the half-life for the slow component was significantly longer than in patients with a negative PSIFT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Assessment of thyroid status by laboratory methods: developments and perspectives.

Serum protein-bound iodine and in vivo radioiodine tests were employed for over three decades although their usefulness was hampered by interference from iodinated compounds. Tests reflecting thyroid hormone action were therefore used for additional information on thyroid status. Competitive saturation analysis of serum T4 was introduced in the 60s. RIAs for T4 and T3 were not developed until ten years later because of problems in raising polyclonal antibodies to small haptens. Methods for FT4 and FT3 based on equilibrium dialysis of serum labelled with radioiodinated hormone emerged in the 60s, and in the 70s sensitive RIAs enabled direct determination of free hormone concentrations in serum dialysate. Dialysis and ultrafiltration methods are tedious and therefore various free hormone indices, based on total hormone concentrations and tests for unoccupied thyroid hormone-binding sites, have been used right up to our times. In the 80s rapid assays for FT4 and FT3 based on varying principles were developed particularly by commercial companies. Free hormone assays utilizing thyroid hormone analogs as tracers have been criticized because binding of analogs to serum proteins results in spurious values in conditions characterized by thyroid hormone-binding protein abnormalities. Bioassay of TSH was not adopted by the clinical service laboratory because of insufficient analytical sensitivity. The first immunological TSH assay, based on cross-reaction of human and bovine TSH in a hemagglutination inhibition test, was also too insensitive for practical purposes. RIAs for direct determination of normal TSH concentrations were developed in the 60s. The breakthrough in measurement of low TSH concentrations occurred in the 80s with the advent of immunometric assays utilizing monoclonal antibodies. Recently chemiluminescence, fluorescence and enzyme labels have been used for the development of non-isotopic methods for thyroid hormones and TSH. Immunoassay systems for bed-side measurement of analyte concentrations are being developed and immunosensors for continuous monitoring of analyte levels will probably be available in the future.

Dialysis↗

Imaging of soft-tissue sarcomas with indium-111-labeled monoclonal antimyosin Fab fragments.

Some soft-tissue sarcomas contain intracellular myosin. We therefore studied the possibility of localizing various soft-tissue sarcomas with 111In-labeled monoclonal antibody Fab fragments binding specifically to myosin, assuming that damage to the cell membrane could expose intracellular myosin. Nineteen patients with different types of soft-tissue sarcomas were studied. Eighteen patients were found to have abnormal antibody uptakes. Antibody uptake was not observed in an additional patient operated for a benign tumor (gastric leiomyoma). The immunoscintigraphy results were generally in good agreement with those of other radiologic findings (computed tomography, ultrasound, magnetic resonance imaging). Surprisingly, the immunohistochemistry results showed that tumors not stainable for myosin can also be imaged with antimyosin. Thus, the mechanism of antibody uptake does not seem to be related entirely to specific antigen recognition. Irrespective of the exact mechanism for the uptake of labeled antibody this method appears to be useful for localizing soft-tissue sarcomas.

Adult↗

The evaluation of a chemiluminescent assay for free thyroxine by comparison with equilibrium dialysis in clinical samples.

We have investigated the diagnostic performance of a chemiluminescence immunoassay for free thyroxine (Ciba Corning Magic Lite) in comparison with equilibrium dialysis. Agreement between the methods was satisfactory across a wide range of samples including those from patients with non-thyroidal illness. The results suggest that the chemiluminescence immunoassay is not subject to the artefacts of widely used analogue tracer methods for free thyroxine estimation.

Adolescent↗

Brain perfusion defect size in SPECT predicts outcome in cerebral infarction.

The results of previous reports on the usefulness of brain perfusion single photon emission computed tomography (SPECT) in predicting the outcome of patients with acute cerebral infarction are conflicting. We therefore studied brain perfusion in 64 patients with a single supratentorial infarction. Contradictory to previous results the perfusion defect volume estimated from transversal and coronal slices correlated significantly with both presenting clinical findings and outcome. Although the clinical status at admission also correlated well with outcome, there was a subgroup of patients in which the favourable outcome was predicted only by SPECT and not by physical or any other examination at admission.

Adult↗

Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura.

Splenic dynamics of 111In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of 111In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 +/- 0.7 min vs. 3.6 +/- 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 +/- 5 min vs. 13.2 +/- 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

Adolescent↗

Diagnosis of acute herpes simplex encephalitis by brain perfusion single photon emission computed tomography.

Brain perfusion was studied in 14 patients with acute encephalitis by use of 123I-iodoamphetamine or 99mTc-hexamethylpropyleneamine oxime and single photon emission computed tomography (SPECT), the first examination being made 4-11 days after onset of encephalitis symptoms. All 6 patients with herpes simplex virus encephalitis (HSVE) had strongly increased accumulation of radiotracer in the affected temporal lobe; in the remaining 8 results were normal. At the time of the first SPECT conventional CT images were normal in all patients. The SPECT abnormality in HSVE gradually converted over 4-10 weeks from increased tracer accumulation to greatly subnormal accumulation. Brain perfusion SPECT may be helpful in the early diagnosis of HSVE.

Acute Disease↗

Localization of human malignant tumors with radioiodinated recombinant tissue plasminogen activator.

Human recombinant tissue plasminogen activator (tPA), labeled with 131I(1.1 to 6.2 mCi) by the iodogen method, was administered intravenously to 15 patients with various soft-tissue malignant tumors after blocking of thyroidal radioiodine uptake. Gamma camera imaging was performed 4 and 24 hr after injection; three patients were also imaged 5 days following injection. We observed accumulation of radioactivity in primary and secondary lesions in 11 patients. In this preliminary study we did not detect any definite association between the magnitude of uptake and type of tumor. Tumors were usually visualized already after 4 hr but the uptake was more intense at 24 hr. The target-to-nontarget ratios at 24 hr, determined by computer analysis of stored images, varied from less than 1.2 to 2.1. This is the first demonstration of accumulation of radiolabeled tPA in malignant tissue. We do not know the mechanism of the uptake but because tPA is known to be avidly bound to fibrin, a component of the stroma of many malignant tumors, it is possible that [131I]tPA is bound to fibrin rather than taken up by the malignant cell; various possible cell uptake mechanisms are discussed. Due to the relatively early maximal uptake of this radiopharmaceutical it will be possible to substitute 123I for 131I, a possibility suggesting a potential clinical use of radioiodinated tPA for the detection of malignant tumors of various origin.

Adult↗

Intestinal accumulation of 111In-granulocytes in patients studied because of occult infection.

111In-granulocyte scintigraphy was performed on 245 patients in whom a localized infection was suspected. In 123 patients scintigraphy was positive and of these 35 (28%) had intestinal accumulations of 111In-granulocytes. Specific local causes for the intestinal uptake of radioactivity were antibiotic associated colitis (eight patients), local pyogenic bowel infection (four patients), systemic disease (two patients), bowel necrosis (two patients), colonic cancer (one patient) and Stevens-Johnson's syndrome (one patient). Nonspecific mechanisms of bowel accumulation were desquamation of labelled granulocytes (12 patients) and bleeding (two patients). In three cases the mechanism of colonic accumulation of granulocytes was not revealed. These results show that unexpected accumulations of labelled granulocytes in the gut is not a rare phenomenon and is often due to clinically significant intestinal inflammation or other disease, especially in patients who do not have signs of respiratory, pancreatic or oesophageal inflammation causing desquamated granulocytes to accumulate in the gut.

Adolescent↗

Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy.

Free thyroxine (FT4) and free triiodothyronine (FT3) concentrations in serum were measured by direct equilibrium dialysis methods in patients receiving thyroxine replacement or suppression therapy. Four of 50 hypothyroid patients euthyroid on replacement therapy (mean thyroxine dose 120 micrograms/day) had supranormal FT4 concentrations, whereas the FT3 concentrations were normal in all. Forty-one of 56 operated thyroid carcinoma patients on suppressive therapy (mean thyroxine dose 214 micrograms/day) had raised FT4 concentrations, whereas the FT3 concentrations was elevated in only one patient. There was a large difference in mean FT4 values for hypothyroid and thyroid carcinoma patients (17.2 vs 29.5 pmol/l), whereas the difference in mean FT3 values was small (5.0 vs 6.1 pmol/l), suggesting a decreased peripheral conversion of T4 to T3 with increasing concentrations of FT4. Serum TSH concentrations, as determined by an immunoradiometric assay, varied from less than 0.02 to 11.9 mU/l in treated hypothyroid patients; 21 patients (42%) had values outside the reference limits. As a single test, serum TSH is therefore not very useful for the assessment of adequate thyroxine dosage in patients with primary hypothyroidism. In thyroid carcinoma patients, the TSH concentrations were less than 0.18 mU/l; 45 patients had values less than 0.02 mU/l indicating sufficient suppression of TSH secretion in the majority of cases. On the basis of these results we recommend the combination of FT3 and TSH tests for monitoring thyroxine replacement and suppression therapy. FT4 appears less useful than FT3 for this purpose even if special reference values values were adopted for each patient group.

Adult↗

Concentrations of iodothyronines in serum of patients with chronic renal failure and other nonthyroidal illnesses: role of free fatty acids.

The mean concentration of free thyroxin (FT4) in serum, as determined by direct equilibrium dialysis, was decreased in patients with chronic renal failure (CRF) and increased in patients with various other nonthyroidal illnesses (NTI). The mean concentration of dialyzable free triiodothyronine (FT3) in serum was equally low in both groups of patients. Patients with CRF of various etiology but a similar degree of renal failure as estimated from serum creatinine assay had very similar concentrations of FT4 and FT3 in their serum. Mean thyroxin (T4) and triiodothyronine (T3) concentrations in serum were decreased in CRF and NTI, whereas the mean reverse-T3 concentration in serum was normal in CRF and increased in NTI. T4-binding globulin and albumin were markedly decreased in CRF and NTI; T4-binding prealbumin was increased in CRF and decreased in NTI. The mean concentration of nonesterified free fatty acids (FFA) in serum was increased in NTI but not in CRF. The weak, but significant, positive correlation observed between FT4 and FFA in serum (r = 0.34, P less than 0.01) in NTI indicates that the increase in serum FT4 in this group of patients could be an effect, at least in part, of FFA competing with T4 for binding sites on serum proteins. The stronger correlation detected between the serum FT4 concentration and the FFA/albumin molar ratio in serum (r = 0.60, P less than 0.001) demonstrates the importance of a low albumin concentration for expression of the effect of FFA on FT4 in severe systemic illnesses.

Adult↗