[Initial symptoms of malignant thyroid tumors: the effect of age and sex in an iodine-deficient region. Experiences with 1116 patients]. / Erstsymptome bei Schilddrüsenmalignomen: Einfluss von Alter und Geschlecht in einem Jodmangelgebiet. Erfahrungen an 1116 Patienten.

Initial symptoms of thyroid cancer were collected and analysed for 1116 patients with thyroid cancer in an iodine-deficient region, retrospectively for the period 1960-80 (604 patients), prospectively for 1981-87 (512). Using the WHO classification, 56.1% of patients had papillary, 32.7% follicular, 4.8% C-cell, 3.7% anaplastic and 2.7% various other malignant tumours. In 40% of all patients the initial sign had been a solitary intrathyroid nodule. Cervical lymph node swelling as initial sign had been significantly more frequent in men (21.1%) than in women (10.3%; P less than 0.003). In patients aged under 40 years the cervical lymph node signs were three times as common as among those over 50 years. Distant metastases as initial sign of papillary carcinoma were seen only in those over 60 years. Tumour stages T3 and T4 were seen significantly more frequently in over 60-year-old (42.2%) than under 40-year-old (25.1%; P less than 0.001), independent of histological type. Composition and initial signs of this patient cohort in an iodine-deficient region differed only slightly from those in an iodine-rich region.

High or low dose radioiodine ablation of thyroid remnants?

The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose 131I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiated pT2-3NoMo thyroid cancer were studied. The uptake was 5%-10% at 24 h. Ten patients received 100 mCi, the others 30 mCi 131I. Three months later all patients received a therapeutic dose of 150 mCi 131I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%-10%. Ten patients received 300 mCi and ten 30 mCi 131I as ablation dose. Three months later all received 300 mCi 131I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24 h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, N X M1 patients the ablation was effective in seven out of ten cases in both groups. If "effective" ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in N X M1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of high and low doses of methimazole in patients with Graves' thyrotoxicosis.

In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.

Effects of intra-arterial prostaglandin E1 in patients with peripheral arterial occlusive disease.

The effects of intraarterially administered prostaglandin E1 (PGE1) on macrocirculatory, microcirculatory and metabolic parameters in patients with peripheral arterial occlusive disease were studied. Nutritive calf muscle blood flow, as determined with the xenon-clearance technique, and muscle tissue oxygen pressure increased markedly in patients with obliterations of the femoral artery. Transcutaneous PO2 as indicator for cutaneous blood flow increased in prestenotic regions dose-dependently whereas there was a clear poststenotic decrease during the infusion period. High lactate/pyruvate ratios in the femoral vein were significantly decreased by PGE1 treatment. PO2 in the femoral vein increased significantly. Thus, PGE1 has some beneficial effects on muscle circulation in these patients.

Increased lung capillary permeability after trauma: a prospective clinical study.

Pulmonary dysfunction and permeability were prospectively studied in a group of severely traumatized patients. Ventilatory parameters (i.e., PaO2/FiO2, dynamic compliance, per cent shunt, and A-a DO2) and extravascular lung water (EVLW) measurements were compared with scintigraphic determinations of pulmonary albumin extravasation. Albumin extravasation data demonstrated a pulmonary capillary permeability increase occurring shortly following trauma. The median albumin extravasation value in the patients within 24 hours of trauma was 3.6 X 10(-5)/sec, compared to a control value of -0.1 +/- 0.7 X 10(-5)/sec. Intermediate levels of albumin extravasation were found in patients studied within 48 hours of total hip replacement (1.6 +/- 0.9 X 10(-5)/sec). Eighty per cent of patients studied within the first 48 hours of their trauma had albumin extravasation values exceeding the upper limit of normal as determined by the control value + 2 S.D. In contrast to albumin extravasation values, the PaO2/FiO2, dynamic compliance, per cent shunt, A-a DO2, and EVLW did not begin to deteriorate significantly until at least 48 hours after trauma. We conclude that severe multiple trauma induces an early increase in pulmonary capillary permeability as measured by albumin extravasation scintigraphy. This change is not detectable with other commonly used measures.

Cerebral dynamics of N-isopropyl-(123I)p-iodoamphetamine.

Temporal changes in the distribution of N-isopropyl-(123I)p-iodoamphetamine (IMP) within the brain are measured with serial tomographic imaging. In the cerebellum there is a decrease in activity of 42% from the early [15-45 min postinjection (p.i.)] to the late (210-240 min p.i.) scan, while in the cortex the decrease is 18%, and in the basal ganglia there is no decrease within this time. In brain tumors there was no IMP uptake in the early as well as in the late scans, regardless of tumor type, perfusion rate, or blood-brain barrier dysfunction. In 11 of 43 patients with a cerebral infarction a real increase of 123I activity (mean +21%) was seen in the late images. This "filling in" phenomena might be useful in selecting patients for bypass surgery. In these patients the diaschisis cerebelli, seen in the early scans, disappeared in the late images. The regional distribution of IMP changes with time; spatial ratios might be blurred by temporal changes. High-flow areas such as visio-auditory centers can be delineated clearly after stimulation in fast early scans; in these areas the pharmacokinetics of 123I are different from other cortex regions. To get the full information from the IMP brain uptake, both spatial and temporal variation must be measured.

[11C-methionine PET, IMP-SPECT, CT and MRI in brain tumors]. / 11C-Methionin-PET, IMP-SPECT, CT und MRI bei Hirntumoren.

11C-labelled L-methionine uptake was measured in 7 patients with brain tumours prior to surgery, and in 2 patients with infarction, using PET. The strongest uptake occurred in tumours with a high grade of malignancy (astrocytoma IV: Tumour/Non-Tumour T/NT = 2.6) while low-grade tumours accumulated less activity (astrocytoma II: T/NT = 1.4). Conventional 99mTc DTPA scans revealed a damage of blood brain barrier (BBB) in 4 patients (2 infarctions) with no or only slight 11C-methionine accumulation, while one patient with negative 99mTc-scan and negative CT accumulated methionine in the tumour region (astrocytoma II). PET, MRI, and CT are complementary with regard to extent of tumour tissue, necrotic areas and oedema. None of the brain tumours or infarcted regions took up IMP (123I amphetamine). The investigated regions showed definite uptake defects ranging from 10-50% if compared with the contralateral side. In view of the chemical pathway of methionine it is concluded that the uptake reflects metabolic activity in brain tumour tissue rather than a diffuse uptake due to BBB damage.

[Determination of liver circulation with radionuclides. I. Modification of 99mTc-MMS accumulation in the liver using drugs]. / Zur Bestimmung der Leberdurchblutung mit Radionukliden. I. Beeinflussung der 99mTc-MMS-Anreicherung in der Leber durch Pharmaka.

The rate constant of liver uptake of 99mTc-labelled millimicrospheres is taken to be a measure of nutritive RES blood supply. Animal experiments were used to determine whether this constant--similar to that of other colloids--is affected by drugs such as heparin or corticosteroids which alter RES function. In rabbits, the scatter of k between individuals is quite large, with a standard deviation of 27%, whereas the scatter within an individual appears to be acceptable (8%). Heparin does not change the value of k significantly, whereas prednisolone in a dose of 40 mg/kg BW--a dose that is normal in bolus therapy--reduces k significantly by 21%. If k is determined during such therapy, its reduction may be due to the pharmacological effect and must not be interpreted as a rejection phenomenon.

[Bone scintigraphy for the staging of lymphogranulomatosis?]. / Knochenszintigraphie zur Stadieneinteilung der Lymphogranulomatose?

The importance of bone scintigraphy for the classification of stages of lymphogranulomatosis is judged differently, the indications in literature are not unanimous. The high sensitivity of this method is uncontested, but it is said to be not very reliable in the exclusion of a bone manifestation because of its low specificness. Bone scintigraphy demonstrates a disturbance in bone metabolism; in clinical examination this has to be checked by X-ray view in order to exclude not tumor-induced reasons for the increased or decreased concentration. In a prospective study we have investigated if this combined radiologic approach allows to use scintigraphy in the classification of stages. Four out of 23 patients in stage I showed a tumor-suspicious scintigram which was confirmed by X-ray examination within 1 1/2 years in two patients. One quarter of 133 patients in stage II and III had a pathologic scintigram. In 34 out of 36 patients who could be followed up, this was confirmed later on by an X-ray finding in the same site. 15 out of 36 patients in stage III with initially normal scintigram showed a conversion to a tumor-suspicious scan during the later course of the disease. The tumor-suspicious scintigraphy found at the time of classification of stages has been confirmed later on by X-ray examination in 91% of our series. So, scintigraphy may be considered to be valuable for the classification of stages. Furthermore the conformity of tumor-suspicious scintigram and bone marrow biopsy was investigated. Whereas in 62% of patients with M+ a bone manifestation could be demonstrated by scintigraphy, only 46% of patients with scintigraphic 0+ showed a histologic manifestation in bone marrow. Consequently, bone scintigraphy cannot be used to demonstrate or to exclude a manifestation in bone marrow. As the metabolism is modified by therapy in case of a demonstrated bone manifestation, scintigraphy should be a sensitive parameter in these cases, too, for an early indication of response to cytostatic treatment. The scintigram became normal in 46 patients coming to a complete remission; eight out of nine patients the scintigraphic findings of whom became worse were non-responders. Five out of twelve patients with unchanged scintigram came to a remission. A normalizing scintigram indicates a response to therapy, whereas a deterioration suggests a non-response. Bone scintigraphy can also be used to judge the success of a cytostatic therapy.

[Dynamic reflux scintimetry for quantifying gastroesophageal reflux in patients with prolonged esophageal transit]. / Die dynamische Refluxszintimetrie zur Quantifizierung des gastroösophagealen Refluxes bei Patienten mit verlängertem ösophagealen Transit.

A combination of a radionuclide transit test and a dynamic gastroesophageal scan was evaluated in normal volunteers, in patients with achalasia treated by pneumatic dilatation (n = 34) or Heller myotomy (n = 21). Interpretation of 31 of 57 examinations done with usual scintiscan was not possible because of too high esophageal tracer retention. Only one case could not be interpreted with the modified technique. Gastroesophageal reflux was detected and quantified in this manner in 8 patients, 6 more than with the usual scintiscan. 7 of these 8 patients have had Heller procedure, 1 patient even combined with fundoplasty.

[Nuclear medicine demonstration of esophageal bile reflux]. / Nuklearmedizinischer Nachweis des ösophagealen Gallerefluxes.

Biliary and pancreatic juice has been implicated as a cause of regional inflammation or carcinoma after gastric surgery. We studied 38 patients after gastrectomy using a modification of cholescintigraphy (185 mBq 99m-Tc-DESIDA i.v.). As soon as the tracer had reached the duodenum, a dynamic study (30 min, 120 frames) was started. Thereafter a static image of the epigastrium and thorax in the anterior view with more than 1000 cts/cm2 was recorded. This procedure was repeated after a meal. Of 29 patients without complaints only 4 had a reflux into the jejunal loop. By contrast in 7 of 9 patients with suggestive symptoms this examination demonstrated bile reflux which reached the oesophagus in 6 cases. A stenosis of the distal oesophagus prevented oesophageal reflux in one patient. 2 patients with oesophageal reflux had a history of oesophageal stenosis and oesophagitis confirmed by endoscopy. The remaining 2 patients without demonstrable reflux had neither oesophagitis nor radiologically verified reflux. Cholescintigraphy as modified by us may detect clinical relevant bile reflux into the oesophagus. This is important for surgeons selecting patients with potential benefit from a reoperation. Since most patients with complaints after gastrectomy have had demonstrable bile reflux, reflux-reducing surgical techniques should be used in all.

[Heart and skeletal muscle scintigraphy with thallium 201]. / Herz- und Skelettmuskelszintigraphie mit Thallium-201.

The regional uptake of Thallium-201 is correlated with the regional distribution of cardiac output in the myocardium as well as in skeletal muscle. Thallium-201 perfusion scans will detect peripheral occlusive arterial disease (POAD) as well as coronary heart disease (CHD). In a prospective study we examined POAD patients and CHD patients by both myocardial and leg stress scintigraphy. In normals the uptake ratio of both calves was 1.03 +/- 0.05 (mean +/- SD), while in all patients with proven POAD the ratio was higher than 1.2. In 12 of 16 patients with myocardial infarction the high ratio indicated a coincidence of POAD and CAD, confirmed by other techniques in all but one patient. In patients with suspected CHD there was an increased ratio in 8 of 21;6 of these patients also had an abnormal myocardial stress scan, while there were only 4 abnormal scans in the 13 patients with normal leg uptake. In 19 of 26 patients with known POAD the myocardial stress scan was abnormal, indicating CHD in 75% of this group. This was confirmed in most patients by coronary angiography. The combination of myocardial and leg stress scan can be carried out without further radiation exposure to the patient and in a few minutes. It is a new approach to determine the possible coincidence between POAD and CHD; it should be performed in all patients referred for TI-201 myocardial stress scintigraphy.

Quantitative determination of regional extravascular lung water and regional blood volume in congestive heart failure.

Regional extravascular lung water (rELW) and blood volume (rBV) in five controls and 14 patients with congestive heart failure (CHF) were measured by constant infusion of H215O and inhalation of 11CO using positron emission tomography (PET). The analysis of 18 regions per patient revealed a relatively homogeneous level of rELW in the controls (mean = 0.11 +/- 0.02 g/cc; range, 0.08-0.21), whereas this increase in patients with CHF (0.17 +/- 0.02 g/cc; range, 0.10-0.51). The rBV was 0.21 +/- 0.02 g/cc in the controls and 0.17 +/- 0.02 g/cc in patients with CHF. A good correlation was found between the severity of chronic heart failure (according to the grading of the New York Heart Association) and mean extravascular lung water (ELW) (r = 0.69), as well as between CHF and the ratio rELW/rBV (r = 0.87); however, the correlation to hemodynamic data was less satisfactory (cardiac index, r = 0.45; pulmonary capillary wedge pressure, r = 0.47; ejection fraction, r = 0.60). In supine controls, a progressive decrease in regional blood volume from the basal to the apical regions was observed, whereas the differences in ELW were only small. In patients with chronic heart failure, ELW in the basal parts was markedly increased, whereas in the apical regions, only minor deviations from the controls were observed. In the basal regions of these patients, the blood volume was reduced by about 30%. Instead of the normal basoapical gradient of blood volume, these patients showed a rather flat distribution. Radiographic findings of pulmonary edema generally appeared together with an ELW level of greater than 0.14 g/cc.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nuclear medicine diagnosis of pulmonary capillary protein leakage]. / Nuklearmedizinische Diagnostik des "Pulmonary Capillary Protein Leakage".

Pulmonary extravascular albumin extravasation in patients with adult respiratory distress syndrome can be quantified with radionuclide techniques. While imaging procedures with a computerized gamma camera will allow reproducible ROIs, this will be the main limitation in nonimaging measurements with small scintillation probes. Repeated positioning by one operator results in a mean spatial variation of position of about 2 cm and a variation in count rate of 25%. For the estimation of PCPL the small probes must be positioned under scintigraphic control. Under these conditions the results of both techniques are identical. The upper limit of normal was estimated to be 1 x E-5/sec. The standard deviation of abnormal measurements was about 10%. The pulmonary capillary protein leakage can be quantified by radionuclide techniques with good accuracy, using the combination of imaging and nonimaging techniques.

[Scintigraphic diagnosis of bile leakage]. / Nuklearmedizinische Diagnostik des Gallelecks.

Specificity and sensitivity of cholescintigraphy for diagnosis of bile leakage were evaluated in a prospective study in 91 patients with partial liver resection and in 64 patients with liver transplantation. Sensitivity was found to be 0.93, specificity in the evaluable scintigrams 1.0. If all non-evaluable scintigrams are considered to be wrong, specificity was 0.83. Cholescintigraphy is a non-invasive method without irritation of the patient with a high specificity and sufficient sensitivity for demonstration or exclusion of a leak. These leaks may arise not only postoperatively but also after biopsies, trauma or spontaneously. In cases of clinical suspicion cholescintigraphy should be used as primary investigational tool.

[Cholescintigraphy for determining focal nodular hyperplasia of the liver?]. / Choleszintigraphie zum Nachweis der focal-nodulären Hyperplasie (FNH) der Leber?

The preoperative diagnosis of a focal nodular hyperplasia (FNH) is of special interest as in case of non-malignancy of this tumor no extirpation has to be carried out. 86 patients - 19 of them suffered from FNH - have been examined by 3 phasecholescintigraphy. There were no false positive findings (specifity 100 per cent). 2 out of 23 examined FNH were not recognized as such (sensitivity 87 per cent) because the tumor had been changed regressive largely. Cholescintigraphy is an excellent method to prove FNH not bothering the patient too much. Cholescintigraphy should be the first measure of differential diagnostic clarification whenever a benign tumor is suspected.