Association of NQO1 polymorphism with spontaneous breast cancer in two independent populations.

Eight different single-nucleotide polymorphisms (SNPs) in six different genes were investigated for possible association with breast cancer. We used a case-control study design in two Caucasian populations, one from Tyrol, Austria, and the other from Prague, Czech Republic. Two SNPs showed an association with breast cancer: R72P inTP53 and P187S in NQO1. Six SNPs, Q356R and P871L in BRCA1, N372H in BRCA2, C112R (E4) and R158C (E2) in ApoE and C825T in GNB3, did not show any sign of association. The P187S polymorphism in NQO1 was associated with breast cancer in both populations from Tyrol and Prague with a higher risk for carriers of the 187S allele. Combining the results of the two populations, we observed a highly significant difference (P=0.0004) of genotype and allele frequencies (odds ratio (OR)=1.46; 95% confidence interval (CI) 1.16-1.85; P=0.001) and of the homozygote ratio (OR=3.8; 95% CI 1.73-8.34; P=0.0001). Combining the two 'candidate' SNPs (P187S and R72P) revealed an increased risk for breast cancer of double heterozygotes (P187S/R72P) of the NQO1 and TP53 genes (OR=1.88; 95% CI 1.13-3.15; P=0.011), suggesting a possible interaction of these two loci.

[18Fluoro-FDG SPECT for the demonstration of hibernating myocardium: an interim account]. / 18Fluor-FDG-SPECT zum Nachweis von hibernierendem Myokard: eine Zwischenbilanz.

AIM: The present investigation demonstrates an intraindividual comparison of FDG-PET and FDG-SPECT. MATERIAL AND METHODS: Thirty patients with CHD and planed revascularisation underwent both modalities. Myocardial perfusion was evaluated by 99mTc-MIBI SPECT. The myocardium was divided into 25 segments and the results were compared by two experienced observers. RESULTS: Segmental concordance of FDG-PET and -SPECT was 94.1%. PET indicated a higher percentage of hibernating myocardium (8.9% vs. 5.7%) and a lower rate of matched defects (11.5% vs. 16.0%). In 22 cases the need for revascularisation was assessed identically. In the remaining 8 patients FDG-PET and FDG-SPECT required an intervention in 6 and 2 cases, respectively. CONCLUSION: The results of FDG-PET and FDG-SPECT showed a high segmental concordance, but the individual assessment of hibernation worthwhile for revascularisation demonstrated important differences in patient management.

[18FDG in the primary staging of lung tumors. Results with a gamma camera and a 511 keV collimator]. / 18FDG beim primären Staging von Lungentumoren. Ergebnisse an einer Gammakamera mit einem 511 keV Kollimator.

The diagnosis of primary lung tumors requires a precise staging according to the TNM classification. In contrast to established imaging methods 18FDG describes the functional metabolic processes in the tumor tissue due to increased glycolysis. This paper describes the use of 18FDG in the primary staging of lung tumors and metastases. 44 patients were studied with a gamma camera and a 511 keV collimator. In comparison to pulmonary tumors and metastases detected by other imaging methods (107) the accumulation of 18FDG has a sensitivity of 85%, in lesions verified by histology (50) of 89%, in primary tumors (35) of 100% and in metastases (63) of 76%. As an alternative to FDG PET studies, primary staging of lung tumors is possible with a gamma camera, suitable for ECT and fitted with a 511 keV collimator.

A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke.

A multicentre, double-blind, randomized study was performed in 179 patients with acute ischaemic stroke resulting in limb paresis. The purpose was to compare the safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT). Prophylaxis started within 72 hours of the onset of stroke and continued for at least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg scanning which, if found positive, was followed by venography. A first computed tomography scan of the brain was performed at screening to rule out cerebral haemorrhage and a second at cessation of treatment to detect any haemorrhagic transformations. At the 2-3-months' follow-up period the patients were examined for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary embolism was diagnosed in one patient in each group. Major conversion to a symptomatic haemorrhagic brain infarct was found in one patient in each group. Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of patients treated with heparin (p = 0.135, NS). Deaths were mainly related to pulmonary infection and cerebral oedema, thus considered to be due directly to the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily is both safe and as effective as 5000 IU of heparin sodium twice daily given for DVT prophylaxis in patients with acute ischaemic stroke of recent onset.

Rapid measurement of blood leakage during regional chemotherapy.

In order to avoid complications after regional chemotherapy (isolated hyperthermic perfusion) of the extremities, rapid measurement of blood leakage from the extracorporeal to the systemic circulation is important. A method using technetium-99m in vivo red blood cell (RBC) labelling is reported that provides results within 3 min. Blood samples drawn from the systemic and the extracorporeal circulation were measured for 99mTc activity using a mobile well counter, and the leakage values calculated. The mean result was 7.6% +/- 6.5%/15 min (n = 209). The corresponding flow rate was 100.2 +/- 85.7 ml/15 min (mean +/- SD). The values for isolation perfusion of the upper and the lower extremities are compared. The leakage results using 99mTc RBC labelling were correlated with other blood pool markers. Iodine-125 human serum albumin and indium-113 m transferrin were administered in subgroups of 4 and 19 patients simultaneously. Using linear regression, the coefficient of correlation was 0.72 for 99mTc/113mIn and 0.58 for 99mTc/125I. Comparison with the alternatives suggests that the rapid method of leakage measurement after 99mTc RBC labelling can be considered one of the most practicable and reliable methods available.

[A phosphine-substituted diphosphonic acid (HMPD) for improved scintigraphic detection of bone lesions]. / Eine Phosphin-substituierte Diphosphonsäure (HMPD) zur verbesserten szintigraphischen Darstellung von Skelettläsionen.

Although the radiopharmaceuticals used for bone scintigraphy are of very high quality, the search for an "ideal" agent continues. To optimise the detectability of bone lesions, we analysed 244 different 99mTc-labeled phosphonates in animal experiments. In osteosarcoma-carrying rats 99mTc-labeled 1-Hydroxy-3-methyl-phosphinic-1, 1-propanediphosphonic acid (HMPD) was shown to produce the best lesion/normal bone ratio. 99mTc-MDP was used as reference. The ratio was found to be 1.28 for 99mTc-HMPD. The transferability of our results in animals to the situation in man was studied in 10 patients with bone metastases. There was for 99mTc-HMPD an improvement of the lesion/normal bone ratio by more than 60% but also an additional reduction of the soft tissue contrast by about 40%. 15% of the metastases were detected by scintigraphy using 99mTc-HMPD only and not with 99mTc-MDP. The new agent should make possible a better and earlier discrimination of bone lesions in the scintigram.

[The detection of inflammation and the formation of HAMA following the administration of monoclonal antibody BW 250/183]. / Entzündungsnachweis und HAMA-Bildung nach Applikation des monoklonalen Antikörpers BW 250/183.

Experiences with the use of the 99mTc-labelled MAb BW 250/183 in the detection of inflammatory lesions are reported. In 160 of 354 investigated patients the results could be confirmed by other methods. The sensitivity (91%) and the specificity (82%) were very high for a diagnostic tool and were comparable with the results of other leukocyte scans as reported in the literature. The positive predictive value of the method was 93%. In 84 patients studied once and in 6 patients studied twice only one case of the latter group showed a positive HAMA response. It may be concluded that the detection of foci of inflammation with the 99mTc-labelled MAb BW 250/183 is of great diagnostic value and that its administration can be repeated without risk.

[Binding of the monoclonal antibody BW 250/183 to human granulocytes]. / Bindung des monoklonalen Antikörpers BW 250/183 an menschliche Granulozyten.

Lately, the specific binding of appropriate monoclonal antibodies to human granulocytes has been used for the scintigraphic detection of inflammatory foci. Using the antibody BW 250/183 we studied the underlying binding kinetics. As an important requirement for a specific cell binding it has been shown that the labelling procedure does not change the immunoreactivity of the antibody. An affinity constant of 2 x 10(9) l/mol has been calculated from binding studies. Usually, 0.25-1.0 mg of the 99mTc-labelled antibody are applied per patient. In the present study an equilibrium in blood appeared quickly after intravenous application; at steady state about one fourth of the activity was cell-bound. The rest of the activity circulated in the plasma in the form of labelled IgG and was able to react directly with those granulocytes which were already accumulated in the inflamed area. Even a drastic reduction of the applied protein mass did not change this equilibrium. The law of mass action seems not to be directly applicable to this problem. Interferences with components of the plasma can be excluded as explanation for this behaviour. After application of in-vitro labelled granulocytes from which unbound antibodies were removed completely by washing, an identical steady state was observed within 10 min after injection; however, in this situation the intravasal residence time of activity increased distinctly.

[Initial experiences with a new monoclonal antibody in diagnosis of malignant melanomas]. / Erste Erfahrungen mit einem neuen monoklonalen Antikörper in der Diagnostik maligner Melanome.

In a study of 17 patients with malignant melanomas in the extremities the sensitivity and specificity of a new monoclonal antibody directed at melanoma cells (BW 575, Behring) were investigated. The specificity was 100%, but the sensitivity 70%. In 3 cases known foci could not be detected. All nodular melanomas and their metastases were detected (9 patients). Repeated examination during the first 24 h after injection of the Tc-99m-marked antibody, and two-plane investigations made it possible to detect even small tumors less than 1 cm in diameter and subcutaneous lesions where the melanomas absorbed the antibodies. Due to its high specificity, the antibody seems to be a promising aid in deciding the operative strategy.

Monoclonal antibody BW431/26 labelled with technetium 99m and indium 111: an investigation of the biodistribution and the dosimetry in patients.

As a competitive diagnostic tool for the detection of malignant tumours and other pathological conditions, monoclonal antibodies have long been established. Herein we give the biokinetic data of the antibody BW 431/26 and the consequent radiation dose to patients. These parameters were recorded in 39 patients, using the antibody labelled either with technetium 99m or indium 111. Remarkable differences were observed between the two radionuclides. Whereas the indium-labelled one showed biexponential elimination kinetics, the technetium-labelled one is eliminated linearly over time. The distribution pattern of the two is identical, although the radiation dose varies quite a lot, being 20-fold higher with indium 111 when total body exposure is taken into account (for 111In the whole-body radiation exposure is 0.1 mGy/MBq; for 99mTc it is 0.0047 mGy/MBq). With respect to these results and considering the general availability of the technetium-labelled Ab, it is the best choice for diagnostic use.

[99mTc-2-methoxy-isobutyl-isonitrile in the diagnosis of coronary heart disease: results of a multicenter study]. / 99mTc-2-Methoxy-Isobutyl-Isonitril in der Diagnostik der koronaren Herzkrankheit: Ergebnisse einer Multizenterstudie.

A total of 226 patients was studied in a phase-III multicenter trial to compare the results of stress/rest 99mTc-MIBI with 201TI scintigraphy and/or coronary arteriography. The evaluation of planar and SPECT imaging was based on a semiquantitative visual scoring. A congruent diagnosis was generated from all planar 201TI and 99mTc-MIBI scintigrams performed in 36 patients. In 62 of 63 patients, SPECT-studies with 99mTc-MIBI and 201TI led to an identical diagnosis. In one patient a positive result was obtained with 201TI-SPECT whereas 99mTc-MIBI was negative. Segmental agreement for 1509 SPECT segments was 85.7%, for 554 planar segments it was 86.6%. In comparison to coronary arteriography, performed in 180 patients, the overall sensitivity for the correct diagnosis of coronary artery disease (CAD) was 86% for planar MIBI scintigraphy or 92% for MIBI-SPECT. Overall specificity was 100% for planar imaging and 57% for SPECT. The low specificity of MIBI-SPECT was probably due to high prevalence of CAD in this study population. In a subgroup of 43 patients, who underwent coronary angiography, identical results were found with 99mTc-MIBI and 201TI. Only one patient showed a positive scintigraphic result with both 99mTc-MIBI and 201TI without angiographically proven stenosis greater than 50% or prior myocardial infarction. Vessel sensitivities in stenosed coronary arteries (greater than 50% stenosis) were 54% for the LAD and 87% for the RCX/RCA areas with MIBI-SPECT, or 51% or 79% for planar scintigraphy, respectively. Vessel specificities for SPECT were 65% in the LAD or 52% in the RCX/RCA, or 90% or 83% in planar imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

[Familial nonneoplastic inappropriate thyrotropin secretion]. / Familiäre, nicht-neoplastische inadäquate Thyreotropin-Inkretion.

A follicular thyroid carcinoma was suspected in a 62-year-old woman after the fifth goitre excision for non-neoplastic inappropriate thyrotropin secretion. Small-follicular adenoma could not be excluded histologically. After an attempt at thyrotropin suppression with L-thyroxine, triiodothyronine, D-thyroxine with L-thyroxine, and bromocriptine had failed, lasting if partial decrease in the maximally elevated TSH levels was achieved with triiodothyroacetic acid (TRIAC). One of the patient's three daughters also has non-neoplastic inappropriate thyrotropin secretion and has had two goitre excisions. It is most likely a familial form of inappropriate TSH secretion.

[Nuclear medicine prediction of histologic tumor response of osteosarcoma]. / Nuklearmedizinische Vorhersage des histologischen Tumoransprechens beim Osteosarkom.

The prediction of histologic tumor response to preoperative chemotherapy was assessed by quantitative scintigraphic follow-up examinations of 54 osteosarcomas. Tumor/non-tumor scintimetry using 99mTc labeled diphosphonates allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (accuracy = 83%) at the half-way stage of preoperative chemotherapy evaluating only those tumors which showed convergent changes of tumor/non-tumor ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc MDP plasma clearance predicted the histologic tumor response to chemotherapy in 12 of 13 tumors (accuracy = 92%) after completion and in all 11 cases (accuracy = 100%) at the half-way stage.

[Age dependence of kidney function]. / Altersabhängigkeit der Nierenfunktion.

Although kidney function is immature in infants and decreases with increasing age in adults, when assessing the kidney clearance, it is not common to make an adjustment for age. On the other hand, correction for the standard body surface is generally accepted. Previous studies have yielded contradictory results, probably due to the small numbers of patients studied. To obtain the statistically significant relationship between age and kidney clearance, we compiled more than 1000 studies. These studies were divided into three groups: (1) children under 2 years of age (n = 71); (2) children and adolescents from 2 to 15 years (n = 64 male/58 female); (3) adults (n = 474 male/424 female; age: 16-80 years). Total clearance determinations were only considered if there were no differences between the two kidneys and if there was no obstruction of micturition or other pathological findings. Surprisingly, the statistical analysis showed no differences in clearance values between sexes. The maximal clearance values were found in the groups with children about 8 years old and the greatest scatter of values was seen in children under 2 years of age (a discrepancy between maturation age and calendar age). The complete set of data was based on the presumption that continuous function consisting of three trunks describes the course of normal kidney clearance in relation to patient age. If one determines an arbitrary reference value (e.g., 25 years), correction factors can easily be derived from the function described in order to compare individual clearance with a normal value.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet scintigraphy in cerebrovascular diseases.

The benefit of platelet scintigraphy using 99mTc-phytate as a method to detect atherosclerotic lesions in extracranial neck vessels was tested on 143 patients. 29 patients had an abnormal scan of the neck vessels. The scintigraphic results were critically evaluated, taking clinical observations and the angiograms performed on 88 patients into consideration. Platelet scintigraphy can be useful as an additional examination in some patients. Generally, however, the value and reliability of platelet scintigraphy must be seen as insufficient, making further prospective studies with histological examinations imperative.

[Use of streptokinase and urokinase in deep venous thrombosis and pulmonary embolism: indications and clinical experience]. / Der Einsatz von Streptokinase und Urokinase bei der tiefen Venenthrombose und Lungenembolie: Indikationsstellung und klinische Erfahrung.

The efficacy of fibrinolysis in DVT is dependent upon the age and organization of the thrombus as well as its localization. In consequence, selective evaluation prior to determining the indication for thrombolytic therapy is just as important for therapeutic success as choosing the appropriate fibrinolytic agent. To improve the results of fibrinolysis a team of angiologists, hemostaseologists, radiologists and surgeons are cooperating in a special "thromboembolic care unit". Phlebographic criteria were defined which allow differentiation of fibrinolytic indications depending upon the site of the thrombus. Selection of the fibrinolytic agent and careful monitoring of the thrombolysis should ensure a maximum therapeutic effect with a minimum of bleeding complications. The duration of thrombolysis was established through phlebographic verification and functional tests with venous occlusion plethysmography. The cause and results of 108 cases of thrombolysis shall be presented.

Iodine-131-labeled diphosphonates for palliative treatment of bone metastases: II. Preliminary clinical results with iodine-131 BDP3.

The kinetics, dosimetry, and response of iodine-131 alpha-amino-(4-hydroxybenzylidene)-diphosphonate ([131I]BDP3) treatment were investigated with patients who had pain symptoms from bone metastases of various primary carcinoma. The blood clearance of [131I]BDP3 was rapid. More than 90% disappeared from the blood pool at 2 hr after injection. The excretion of the activity occurred solely through the kidneys and mean total-body retention at 48 hr was 48.6%. The urinary activity showed a metabolite which must be formed by an in vivo cleavage reaction of a phosphorus-carbon bond. The uptake of in vivo cleaved [131I]iodide in the unblocked thyroid was approximately 0.5%. The effective half-life of [131I]BDP3 in metastatic bone (median 182 hr; range 177-205 hr) proved to be longer than in unaffected areas (145 hr; 140-165 hr). Palliative therapies were performed with 18 patients. They received doses ranging between 6 and 48 mCi [131I]BDP3. The response was 44% complete pain relief, 6% substantial pain relief, 22% minimal improvement, and 28% no change. The duration of response ranged between 1 and 8 wk.

Multiple extra-adrenal and thoracic pheochromocytomas.

On the basis of a case of multiple, extra-adrenal intrathoracic pheochromocytomas (total of 6 tumors), the value of dynamic computerized tomography investigations, venous sampling, scintigrams with 131I-meta iodobenzylguanide, and selective arteriography is discussed.

Investigations on the effect of metamizol on ureteral motility.

The aim of this comparative study was to obtain quantitative information on the effect that metamizol has on ureteral motility. Renal Tc-99m-MDP excretion and ureteral urine transport against gravity were examined in five patients, once without (control) and, several days later, with metamizol treatment. In each of these ten scanning sessions, renograms of both kidneys were recorded. They were corrected for background activity and compared with respect to the following parameters: the curve amplitude at 30 min p.i. normalized to the respective maximum amplitude; the 6-30 min and 40 s-6 min integrals of a corrected curve. Under metamizol medication, the flow of radioactivity to the bladder was thus found to be significantly reduced (p less than 0.001). The comparison of the Tc-99m-MDP retention curves obtained with and without metamizol treatment did not reveal a statistically significant drug effect on renal Tc-99m-MDP excretion.