Bone minerals and levothyroxine.
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Biomedical subjects
Publications and source records attributed to W Börner.
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Thirty patients with clinically suspected infective endocarditis were scanned with Indium-111- or Tc-99m-HM-PAO-labeled granulocytes. The scans were correlated with the clinical course, and in 20 cases with the results from histologic examination of the valves. In six cases the scintigraphic examination gave correct positive results, in three cases false negative, in one case a false positive, and in 20 cases correct negative results. If we limit the analysis to only the histologically proven cases, our data suggest a specificity of the method of 86% and a sensitivity of about 67%.
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In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111In-labeling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.
To investigate the influence of calcitonin deficiency on bone turnover and density we studied 25 premenopausal female and 12 male patients (age 23 to 49 years) who had undergone total thyroidectomy for differentiated thyroid cancer 1 to 15 years previously. Basal and calcium stimulated extractable calcitonin, representing the monomeric, biologically active form of the hormone, was lacking or markedly decreased in all patients. There was a relative increase of urine hydroxyproline excretion (an index of osteoclastic bone degradation) in relation to serum osteocalcin (an index of osteoblastic bone formation) indicating an imbalance of bone turnover with a tendency to increased degradation in all patients. Total and trabecular bone density, measured with quantitative computed tomography at the distal forearm were significantly decreased in the male and normal in the female patients, without a relation to the duration of the calcitonin deficiency. The study indicates that patients with calcitonin deficiency, suppressive thyroid hormone treatment, or both may have a higher risk of increased bone degradation and osteopenia. Whether the effect is more due to calcitonin deficiency or thyroid hormone therapy, cannot be concluded from this study design. The fact that only the male patients had a decreased bone density may be due to a lower parathyroid activity in our female patients and the greater thyroidectomy-induced decrement of monomeric calcitonin in our male patients compared with male controls.
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Some years ago we designed a special purpose gamma-ray QCT scanner for bone mineral measurements at the forearm. Currently, the first commercially built scanners (Stratec SCT 900) are being tested and clinically evaluated. The scanner uses an 125I photon source with a multidetector translate rotate fan beam geometry and newly developed semiconductor crystals. Quantification of trabecular bone and total bone at a standardized radial cross section gives an in-vivo reproducibility of less than 1%, which is superior compared to all other bone mineral measurement techniques. In-vitro reproducibility is between 0.2 and 0.4%, measured with calibration phantoms. The high in vivo reproducibility is ensured by automatic contour finding algorithms to determine the bone mass within a forearm cross sectional slice. A number of healthy men (n = 201) and women (n = 400) were examined to obtain a reference population for comparison to patients with generalized bone disease. We compared 182 osteoporotic females with healthy subjects. The high precision of the device and the high sensitivity of the measurement site considering changes of trabecular bone mass provide a very powerful means for monitoring bone mineral loss or changes due to therapy, as well as high diagnostic sensitivity.
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The lipophilic 99mTc-HMPAO complex can be used for labelling platelets as well as granulocytes. Platelets were isolated according to standard isolation procedures for the evaluation of the optimal labelling parameters. The labelling efficiency (%) depends on incubation temperature (22 degrees C: 40%: 37 degrees C: 50%), incubation time (3 min: 20%, 25 min: 55%) and the incubation medium (plasma: 40%; saline 50%). The 60 min 99mTc elution out of the platelets ranged around 8%. The platelet recovery used as a quality control parameter is around 25% +/- 4% and is stable for at least 240 min. The high elution rate out of the platelets leads to renal excretion of the label and hence to significant kidney and bladder activity. Intestinal excretion of the label can also be frequently demonstrated. Fresh thrombotic lesions can normally be detected 4 h after reinjection of the labelled platelets, and in some patients as early as 1 h after reinjection. In conclusion, 99mTc-HMPAO seems to be a promising platelet label for imaging thrombotic lesions but not for platelet survival studies, because of the short physical half life of 99mTc.
Twenty-five patients were examined in vivo with 99mTc labelled monoclonal antibodies; 15 with suspected infections with an antigranulocyte antibody (BW 250/183), 10 with suspected recurrence of a colorectal carcinoma with an anti CEA antibody (BW 431/26). Both antibodies were IgG1 isotypes. In the patients with suspected infections no change of the peripheral leukocyte count could be observed after the antibody injection (1 mg, n = 9; 0.5 mg, n = 1; 0.25 mg, n = 6). In 2 patients examined with the anti CEA antibody (2 mg), a significant decrease of the peripheral leukocyte count could be observed. The recovery rate of the 99mTc antibody labelled granulocytes was calculated to be about 10%. The increase of the antibody-antigen binding was calculated to be 0.2%/min. In vivo the organ distribution curves demonstrated an increase of 99mTc activity over spleen and bone marrow of 1.1%/min, which was interpreted as antigen-antibody reactivity. The organ distribution curves of the anti granulocyte antibody over spleen and bone marrow showed typical binding characteristics to the local granulocyte epitopes. The curves over other organs showed a simple perfusion pattern. The curves of the anti CEA antibody showed a perfusion pattern over all the examined organs. A sham dialysis model in one patient with renal insufficiency undergoing regular dialysis treatment demonstrated the viability of 99mTc antibody labelled granulocytes in vivo. The kinetic patterns of the 99mTc antibody in patients with Crohn's disease were interpreted as CEA binding of the antibody in the bowel wall.
A prospective study in 38 patients was designed to evaluate the efficacy and reliability of radionuclide hysterosalpingoscintigraphy (HSS) using 99mTc labelled human albumin macroaggregates (HAMA). Following application in the posterior vaginal fornix at the time of ovulation, HAMA normally migrate spontaneously through the uterus and tubes and may be identified after 20 min (range 5-90 min) in the uterine cavity and after 2 hrs (range 40 min - 3 hrs) in the free pelvis, using a gamma camera. When correlated with the findings of conventional contrast hysterosalpingography (HSG), the radionuclide procedure yielded comparable results in females with patent or clearly obstructed tubes. Using 8-10 MBq 99mTc, radiation exposure was estimated to be 0.75 cGy per ovary, which is considerably less than the mean dose absorbed with HSG. As the HSS procedure imitates the migration of spermatozoa by the means of an inert tracer, it allows a direct insight in the mechanisms of passive transport taking place in the uterus and tubes at the period of ovulation. Thus, it reflects the physiological state of the female reproductive tract. On the basis of the scintigraphic findings, equivocal results on HSG have to be re-evaluated, as tubes, which are anatomically patent under high pressure, may be functionally deficient.
A sonographic grey scale (gs) analysis of the thyroid gland was retrospectively (1985-1986) performed in 248 patients with normal sized thyroid glands or "diffuse" thyroid diseases. During the examination the physical parameters for gain, far and near gain were constant. The normal value (means +/- 2 s) in 95 patients with normal sized and euthyroid thyroid glands was lower in females (gs: 14 +/- 4) than in males (gs: 16 +/- 6), children had obviously lower patterns (gs: 7.1), adolescents had low normal patterns (gs: 11). The echogenicity increased with increasing thyroid volumes. In patients with autoimmune thyroid diseases an obvious low echogenicity could be demonstrated (Hashimoto's thyroiditis, gs-SEM: 8.3 +/- 1.5; Grave's disease, gs-SEM: 6.7 +/- 1.2) (SEM = standard error of the mean). Euthyroid patients with microsomal antibody titers showed low normal grey scale patterns (gs: 10.9 +/- 3). In patients after subtotal thyroidectomy the grey scale pattern decreased with decreasing volume of the residual thyroid gland. The grey scale pattern increased years after surgery. The subjective grading of the grey scale pattern was different from the quantitatively measured pattern in 18% of the patients with glands of normal size.
31 patients with suspected septic loosening of an endoprosthesis (hip endoprosthesis n = 30; knee endoprosthesis n = 1) were examined with leukocyte scans (10 MBq 111In-oxine: n = 22; 300 MBq 99mTc-HMPAO: n = 9). The results were compared with results of the bacterial growth (n = 22), the histology (n = 12) and of the bone scans (99mTc-MDP: n = 20) which were performed within 4 days. The sensitivity of the bone scan was 100%, the specificity 30% and the diagnostic accuracy regarding a septic loosening of the arthroplasty was 55%. For the leukocyte scans a comparable sensitivity of 100%, but a higher specificity (86%) and accuracy (91%) could be calculated. A false positive leukocyte scan could be observed in a periprosthetic granuloma, an ossifying periarthritis and in a patient with negative bacterial growth with the histological proof of an inflammation.
In seven febrile patients undergoing regular dialysis treatment, sham-dialysis with a dialyzer equipped with a cuprophane membrane was performed during a routine 111In-oxine white blood cell scan with "pure" granulocytes isolated on a discontinuous gradient (Percoll/plasma: n = 5; Metrizamide/plasma: n = 2). The patients were in contact with the cuprophane membrane over 45 or 90 min. Twenty-five (+/- 5) minutes after the start of the dialysis, the peripheral leucocyte count (59 +/- 22%) and the 111In activity in the peripheral blood decreased to a minimum of their initial range (64 +/- 21%) because of leucocyte activation. The activity over both lungs increased symmetrically (29 +/- 15%), the spleen activity decreased (14.8 +/- 8%) and the liver activity remained constant. At the end of the dialysis (45-90 min post-injection), the number of circulating neutrophils, peripheral 111In activity and activity distribution in the organs regained their initial level. In conclusion, these data confirm previously described data concerning the sequestration of neutrophils into the lung during dialysis treatment. The data demonstrate the origin of the activated neutrophils in the circulation and the spleen. The identical behaviour of 111In-oxine-labelled and unlabelled granulocytes is demonstrated. Additionally, the accumulation of activity in the spleen is due not to opsonized cells but to sequestrated neutrophils, which are able to migrate from the spleen after adequate activation. The migration of activated cells into the lung explains the diagnostic difficulties posed by diffuse lung uptake in leucocyte scans in patients with leucocyte-activating diseases.
In the follow-up of five patients with histologic proven medullary thyroid carcinoma (MTC) and raised serum calcitonin and CEA levels the pentavalent Tc-99m-(V)-DMSA and the Tc-99m-MDP bone scan had the highest sensitivity in the localisation of metastases. Both methods are not tumor specific. A false positive Tc-99m-(V)-DMSA uptake in an old osteomyelitis of one vertebra could be demonstrated. The J-123-MIBG and In-111-F(ab2)' antibody scan did not allow to localise one of the above described metastases. In conclusion in the follow-up of patients with MTC and elevated tumor marker concentrations the Tc-99m-(V)-DMSA and the Tc-99m-MDP bone scan should be the second diagnostic procedures after sonography has been performed.
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