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Biomedical subjects

K Liewendahl

Publications and source records attributed to K Liewendahl.

At least 37 records · Page 2Linked to original sources

Thyroid status of patients receiving long-term anticonvulsant therapy assessed by peripheral parameters: a placebo-controlled thyroxine therapy trial.

Thyroid hormone concentrations and measures reflecting thyroid function were studied in sera from 35 patients receiving long-term phenytoin (PHT) or carbamazepine (CBZ) therapy. The mean concentrations of T4, FT4, FT3, and rT3, but not T3, of these patients were significantly lower than those of 19 controls of similar age and sex distribution. The mean serum thyrotropin (TSH) concentration was slightly but significantly higher in patients than in controls, but the serum TSH response to TRH was not significantly increased. In patients, the higher mean clinical diagnostic index of hypothyroidism (CDI-HT: -20.3 +/- 19.1 vs. -33.7 +/- 8.5, p < 0.05) and higher ratio of preejection period to left ventricular ejection time (PEP/LVET: 0.343 +/- 0.065 vs. 0.334 +/- 0.030, p < 0.05) than in controls were compatible with tissue hypothyroidism. However, comparison of the mean levels of alanine aminotransferase (ALAT), creatine kinase (CK), creatinine, triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, osteocalcin, procollagen type III aminoterminal propeptide, and somatomedin-C showed no significant differences between patients and controls. The increased mean angiotensin convertase and sex hormone-binding globulin (SHBG) levels, typical of hyperthyroidism, were probably caused by drug effects. Fourteen patients with a subnormal FT4 concentration in serum participated in a double-blind thyroxine treatment cross-over study. Neither the mean CDI-HT score, nor the systolic time intervals were significantly different between the thyroxine and placebo periods. Five patients benefited subjectively from the treatment. On the basis of all data from the cross-sectional and thyroxine treatment studies, we conclude that patients receiving anticonvulsant drugs chronically are eumetabolic and do not need thyroxine supplementation.

Adult↗

Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders.

Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI.

Adult↗

Automated and manual serum free thyroxine assays evaluated with equilibrium dialysis.

Two fully automated serum FT4 assays (Ciba Corning: ACS-180; Abbott Diagnostics: IMx) and two manual/semiautomated assays (Wallac: Delfia; Diagnostic Products Corp.: Coat-A-Count) were compared with a FT4 reference method based on equilibrium dialysis (ED) using routine clinical samples (n = 105-150). For the full range of FT4 concentrations the correlation with ED was good (r = 0.932-0.959), except for Coat-A-Count (r = 0.852), a single-step analogue-type method. Analytical inaccuracy of the automated methods at low FT4 concentrations was revealed by the differential plot: the IMx assay overestimated concentrations < 10 pmol l-1 and the ACS-180 assay concentrations < 6 pmol l-1. The between-assay CVs for the automated methods were not better than for the non-automated assays indicating problems of calibration curve stability for the automated assays.

Autoanalysis↗

Radioimmunodetection of malignant solid tumours.

An increased clinical utility of radiolabelled monoclonal antibodies (MoAb), recognizing a variety of different antigens expressed preferentially in malignant tissue, for localizing primary, metastatic and recurrent cancer has been documented in many recent investigations. This review focuses on both basic and practical aspects of radioimmunodetection in oncology and is a status report on the performance and limitations of radiolabelled antibody procedures currently applied to the clinical detection of malignant solid tumours. At this time clinically validated radioimmunodetection methods are available for colorectal, ovarian, breast, lung, thyroid medullary, and head and neck carcinoma, and melanoma. Recent advances in humanization of MoAb significantly improve the prospects of effective antibody-guided radiotherapy in the near future.

Animals↗

Localization of hepatic metastases by radiolabelled anti-carcinoembryonic antigen antibody and meta-iodobenzylguanidine in a patient with medullary thyroid carcinoma.

Sonography, computed tomography and magnetic resonance imaging examinations did not detect recurrence or metastases of medullary thyroid carcinoma (MTC) in a patient with a rapidly rising serum calcitonin concentration after total thyroidectomy. Scintigraphy with technetium-99m labelled anti-carcinoembryonic antigen antibody, 99mTc-colloid and iodine-131 metaiodobenzylguanidine indicated liver metastases. The three scintigrams were to some extent discrepant but from the combined information the diagnosis of hepatic metastases could be established; it was subsequently verified by sonography and aspiration biopsy. This case demonstrates the usefulness of applying nuclear medicine imaging methods for the localization of hepatic MTC metastases.

3-Iodobenzylguanidine↗

Validation of quantitative brain dopamine D2 receptor imaging with a conventional single-head SPET camera.

Phantom measurements were performed with a conventional single-head single-photon emission tomography (SPET) camera in order to validate the relevance of the basal ganglia/frontal cortex iodine-123 iodobenzamide (IBZM) uptake ratios measured in patients. Inside a cylindrical phantom (diameter 22 cm), two cylinders with a diameter of 3.3 cm were inserted. The activity concentrations of the cylinders ranged from 6.0 to 22.6 kBq/ml and the cylinder/background activity ratios varied from 1.4 to 3.8. From reconstructed SPET images the cylinder/background activity ratios were calculated using three different regions of interest (ROIs). A linear relationship between the measured activity ratio and the true activity ratio was obtained. In patient studies, basal ganglia/frontal cortex IBZM uptake ratios determined from the reconstructed slices using attenuation correction prior to reconstruction were 1.30 +/- 0.03 in idiopathic Parkinson's disease (n = 9), 1.33 +/- 0.09 in infantile and juvenile neuronal ceroid lipofuscinosis (n = 7) and 1.34 +/- 0.05 in narcolepsy (n = 8). Patients with Huntington's disease had significantly lower ratios (1.09 +/- 0.04, n = 5). The corrected basal ganglia/frontal cortex ratios, determined using linear regression, were about 80% higher. The use of dural-window scatter correction increased the measured ratios by about 10%. Although comprehensive correction methods can further improve the resolution in SPET images, the resolution of the SPET system used by us (1.5-2 cm) will determine what is achievable in basal ganglia D2 receptor imaging.

Brain↗

Radioimmunodetection and radioimmunotherapy of malignant melanoma. A review.

Radioimmunodetection utilizing monoclonal antibodies to various melanoma-associated surface antigens has been studied by several investigators during the past ten years. In the early trials, antibodies were labeled with 131I or 111In, but now 99mTc is almost exclusively used because of its more favorable energy for gamma camera imaging. Excellent specificity has been achieved in most studies, whereas sensitivity has been less good. In a recent European multicenter study on 493 patients sensitivity was 79% and specificity 96%. In this largest study on melanoma so far performed many previously unknown metastatic deposits were identified indicating that radioimmunodetection has a role in the management of metastatic disease. The clinical utility of immunoscintigraphy in localization of regional lymph node metastases has been documented in several investigations in recent years, indicating that this method can be used in the preoperative evaluation of patients. Radioimmunodetection has also been successfully used in the differential diagnosis of ocular lesions. However, conclusive evidence of improved patient outcome resulting from the earlier detection of melanoma lesions by immunoscintigraphy is still lacking. Anti-melanoma antibodies labeled with alpha- and beta-emitting isotopes are potential therapeutic agents, but so far there is little clinical experience with radioimmunotherapy of metastatic melanoma.

Eye Neoplasms↗

Radioimmunoimaging of non-small cell lung cancer with 111In- and 99mTc-labeled monoclonal anti-CEA-antibodies.

Radiolabeled monoclonal anti-CEA antibodies were used for radioimmunolocalization (RIL) of non-small cell lung cancer; in 30 patients with 111In labeled anti CEA F(ab')2 fragment (BW 431/31) and in 16 with 99mTc-labeled intact MoAb (BW 431/26). RIL results were compared with those of other imaging modalities. Paraffin sections from some patients were also studied immunohistochemically using anti-CEA antibody. Patients with 111In labeled MoAB were imaged twice 1-4 days after injection and for image enhancement pulmonary and liver/spleen subtraction were performed. Twenty-seven of 28 primary tumors were positive and metastases were detected in all patients. The total number of lesions was 78 of which 61 (78%) could be detected by RIL. For verification CT was applied to the study of 46 lesions detected by RIL. We found 6 unknown lesions subsequently verified histologically. Using subtraction techniques we detected 9 lesions in 4 patients, later verified as pulmonary metastases, not detected in unprocessed images. Pleural, mediastinal and pericardial lesions were also better delineated in subtracted images than in unprocessed images. Imaging of non-small cell lung cancer with 99mTc-labeled MoAB was performed twice 4-24 h after injection. RIL results were compared with other imaging methods; CT US, conventional radiography, and immunohistochemistry. Twelve out of 16 patients with suspected or known lung cancer had positive immunoscintigrams; 19 of 25 lesions could be detected by RIL. There were 5 false positive and 2 true negative findings. Immunoperoxidase (IP) stainings of paraffin sections of the tumours from 7 patients were performed using two different anti-CEA antibodies; BW 431/26 and ZCEA1. None of the seven tumors examined by immunohistochemistry were negative when stained by BW 431/26, which was the antibody used for immunoscintigraphy.

Adult↗

Interictal brain 99Tc-HM-PAO SPECT hypoperfusion in patients with unstable partial epilepsy and normal CT.

Brain perfusion was studied interictally with 99mTc-HM-PAO SPECT in 47 adult patients with partial epilepsy and normal brain CT. Epilepsy was classified as secondarily generalized in 24 patients, as complex partial in 17 patients and as simple partial in 6 patients. In 24 patients good seizure control was not achieved as these patients had a median number of 78 seizures during the preceding month, while in the rest of the patients seizure control was relatively good (less than 6 seizures during preceding month). Local brain hypoperfusion was observed in 41 or 87% of the patients. Hypoperfusion was located close to the EEG foci in 76% and equally often with temporal and frontal foci. Hypoperfusion and the EEG focus were located on the same side in 83%. Hypoperfusion was more frequent in secondarily generalized epilepsy and simple partial epilepsy than in complex partial epilepsy. Left-sided hypoperfusion was especially associated with complex partial epilepsy. It is likely that the significant epileptogenic brain area was revealed in patients with SPECT focus and EEG focus in the same brain area. In one of our patients MRI showed a small temporal lesion which on successful removal was identified as a low-grade oligodendroglioma. Abnormalities of regional brain uptake of HM-PAO demonstrated by SPECT in patients with partial epilepsy and normal brain CT give further information about pathophysiology in partial epilepsy; this may be of use both for selecting appropriate therapy and in presurgical localization of foci.

Adult↗

Fatty acid-induced increase in serum dialyzable free thyroxine after physical exercise: implication for nonthyroidal illness.

In 14 healthy males, prolonged running exercise resulted in a mean 25% increase in serum free T4 (FT4) concentration (P less than 0.001) which was significantly correlated (P less than 0.01-0.02) with an over 5-fold increase in the concentration of serum FFA and the FFA/albumin molar ratio. Hemoconcentration, as reflected in a mean 19% increase in serum albumin, caused an increase in serum T4-binding globulin and therefore also in serum total T4. As there was no change in the serum T4/T4-binding globulin molar ratio, the rise in serum FT4 was probably not caused, or only partly caused, by an exercise-induced shift of T4 from the extravascular to the intravascular compartment. Neither is it likely that the mean 41% increase in serum TSH observed after exercise, partly owing to hemoconcentration, was the reason for the increase in serum FT4 and T4 as there was no correlation between the increases in the TSH and thyroid hormone levels. Further support for the assumption that the elevation in serum FT4 after exercise was FFA-induced was provided by the observation that addition of 2.5 mmol/L oleic acid to normal serum in vitro resulted in a 33% increase in serum FT4 (P less than 0.001). There is an association between increased concentrations of serum FT4 and unsaturated FFA in patients with various nonthyroidal illnesses according to earlier observations, but it is unlikely, in the light of the present data from healthy subjects, that FFA are directly involved in raising the serum FT4 concentration in nonthyroidal illnesses patients unless the serum FFA concentration exceeds 2 mmol/L or the FFA/albumin molar ratio rises above 2.5.

Adult↗

Platelet splenic transit times in idiopathic thrombocytopenic purpura. Compartmental vs. non-compartmental model.

Platelet splenic transit times following injection of autologous or homologous 111In-labeled platelets were studied in 42 patients with idiopathic thrombocytopenic purpura. The transit times were determined by two methods from the splenic time-activity curves recorded with a gamma camera: closed two-compartmental model and non-compartmental model (deconvolution analysis). By compartmental analysis the mean splenic transit time for platelets was 6.3 +/- 0.3 min (mean +/- S.E.) and by non-compartmental analysis 7.6 +/- 0.4 min for all cases studied. The mean splenic transit time for autologous platelets was significantly (p less than 0.001) shorter (5.1 +/- 0.3 min) in patients with platelet-associated IgG (measured by platelet suspension immunofluorescence test) than in those with no autoantibodies (7.1 +/- 0.4 min), when the compartmental model was employed. There was no significant difference between mean transit times for autologous platelets in antibody positive and negative patients when deconvolution analysis was applied, but the residue of the splenic transfer function was lower for antibody positive than negative patients (7.2 +/- 1.0% vs. 11.7 +/- 1.6%, p less than 0.05). It is concluded that in idiopathic thrombocytopenic purpura the presence of platelet-associated autoantibodies expands the splenic platelet pool and reduces recirculation of platelets.

Adolescent↗

99Tcm-HMPAO SPECT in suspected dementia.

To evaluate the usefulness of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in suspected dementia we studied 160 consecutively imaged elderly patients from our hospital's memory disorder clinic. The diagnosis was based on clinical data, laboratory tests, neuropsychological examination, computed tomography (CT) and EEG. The patients were divided into six diagnostic categories: Alzheimer's disease (AD), multi-infarct dementia (MID), frontal lobe-type dementia (FTD), vascular encephalopathy not fulfilling the criteria of dementia, specific organic conditions, and psychiatric disorders. SPECT images were assessed without knowing the clinical diagnosis, and divided into AD pattern, FTD pattern, MID pattern, abnormal but unclassifiable, and normal. Twenty-three of 36 patients with clinical AD, 25/33 patients with clinical MID, and 2/5 patients with clinical TFD had compatible SPECT patterns. SPECT distinguished AD from MID in the majority (80%) of cases. In patients with depression or anxiety SPECT was abnormal in 16/21 cases, suggesting that SPECT may give early clues to the presence of an underlying organic disease in such elderly patients. Thus, SPECT with 99Tcm-HMPAO seems to be useful in the diagnosis of suspected dementia.

Aged↗

Hormonal changes in severely uncontrolled type 1 (insulin-dependent) diabetes mellitus.

To investigate endocrinological changes associated with severely uncontrolled type 1 (insulin-dependent) diabetes mellitus 27 patients (19 men, eight women) with ketoacidosis or severe ketonuria (= group 1) were examined on admission and after recovery. For comparison 13 non-ketotic patients (seven men, six women), admitted for adjustment of treatment because of poor diabetic control (= group 2), and 20 healthy controls were studied. On admission, the serum testosterone levels in men were lower in group 1 (15.1 +/- 2.0 nmol l-1) (mean +/- SEM) than in group 2 (27.2 +/- 2.8 nmol l-1) (p less than 0.01) and healthy controls (20.6 +/- 2.0 nmol l-1) (p less than 0.05). During treatment the testosterone levels in group 1 rapidly rose to the control level. The serum oestradiol levels in women were low in group 1 both on admission and discharge. The serum prolactin levels were low in female patients in group 1 (119 +/- 17 mIU l-1) compared with the women in group 2 (315 +/- 75 mIU l-1) (p less than 0.05). On admission the serum cortisol levels were higher and their response to 1 mg of dexamethasone was weaker in group 1 than in group 2 and healthy controls. After recovery the serum cortisol levels fell by 15% (p less than 0.01) and the response to 1 mg of dexamethasone returned to normal in group 1. In group 1 during treatment the serum free T4 and reverse T3 levels fell, and the T3 levels rose, whereas the thyroid stimulating hormone (TSH) levels and their responses to TRH remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunolymphoscintigraphy and immunoscintigraphy of ovarian and fallopian tube cancer using F(ab')2 fragments of monoclonal antibody OC 125.

We have used immunolymphoscintigraphy (ILS) alone or in combination with immunoscintigraphy with 131I-labeled F(ab')2 fragments of monoclonal OC 125 antibodies to improve detection of retroperitoneal lymph node metastases of ovarian and fallopian tube cancer. ILS was carried out with bilateral dorsopedal s.c. injections on nine patients and with bilateral iliopelvic injections into the ischiorectal fossa on two other patients. Radioimaging was performed 2-4 times between 0 and 5 days. An additional dose of labeled antibody fragments was given i.v., and imaging was done 2-3 days later. Conventional immunoscintigraphy without preceding ILS was carried out on another nine patients. Dorsopedal ILS improved detection of pelvic and paraaortic lymph node metastases. Malignant lymph nodes were detectable as early as 3 h after s.c. injection of the tracer. Combined results of ILS and immunoscintigraphy in 16 surgically verified cases indicated a true positive finding in 9 patients, true negative finding in 5, false positive in one, and false negative in 1. Calculated from these figures the sensitivity, specificity, and accuracy of the method were 90, 83, and 88%, respectively. Involved lymph nodes were found more frequently in those patients whose serum CA 125 concentration was elevated demonstrating that an elevated serum CA 125 level does not preclude successful radioimmunodetection.

Adult↗