BACKGROUND AND PURPOSE: The initial angiographic occlusion rate is the strongest predictor of later rebleeding in previously ruptured coil-embolized cerebral aneurysms. Angiographic estimations of aneurysmal occlusion rates are, however, subjective in nature and confounded by methodologic problems. COR has been developed, and its superiority has been experimentally established to overcome subjective bias. The purpose of this study was to assess the clinical value of COR as a more objective predictor of aneurysm rebleeding when compared with SOR as described in the Raymond Classification. MATERIALS AND METHODS: We applied COR in a consecutive series of 249 patients. Two DSA projections were selected independently by 2 blinded investigators. In cases of disagreement on the selected projections, a consensus decision was obtained. SOR were determined by 2 independent observers according to the Raymond classification. COR was measured by 2 blinded investigators. Interobserver variations were determined for SOR and COR. COR results were compared with SOR results and stratified as 100%, 99.9%–90%, 89.9%–70%, and <70% occlusion. SOR and COR were evaluated as predictors for aneurysm rebleeding. RESULTS: Seven aneurysms rebled (2.8%; follow-up, 59 ± 35 months). In 20.9% of all cases, DSA selection was performed by consensus evaluations. Interobserver variations were statistically significant for SOR (P = .0030) but not for COR (P = .3517). Compared with COR, SOR overestimated the degree of aneurysmal occlusion in 81.9% of all cases. Only COR predicted rebleeding (P = .0162). CONCLUSIONS: Unacceptable interobserver variations were shown for the standard SOR estimations. COR substantially reduced the impact of subjective bias. COR may, therefore, serve as an easily applicable more objective predictor of aneurysm rerupture. The remaining bias of COR, caused by 2D image analysis, may be overcome by use of direct 3D measurements.

Aim: We compared and delineated possible differences of model-based analysis of ECG-gated SPECT using Tc-99m-sestamibi (Tc-SPECT) with ECG-gated F-18-fluorodeoxyglucose-PET (FDG-PET) for determination of end-diastolic (EDV) and end-systolic (ESV) cardiac volumes, left ventricular ejection fraction (LVEF), and myocardial mass (LVMM). Patients, methods: 24 patients (21 men; age: 54 +/- 12 years) with coronary artery disease underwent Tc-SPECT and FDG-PET imaging for evaluation of myocardial perfusion and viability. By using model-based analysis EDV, ESV, LVEF and LVMM were calculated from short axis images of both Tc-SPECT and FDG-PET. Results: Left ventricular volumes by Tc-SPECT and FDG-PET were 176 +/- 60 ml and 181 +/- 59 ml for EDV, and 97 +/- 44 ml and 103 +/- 45 ml for ESV respectively, LVEF was 47 +/- 8% by Tc-SPECT and 45 +/- 9% by FDG-PET. The LVMM was 214 +/- 40 g (Tc-SPECT) and 202 +/- 43 g (FDG-PET) (all p = NS, paired t-test). A significant correlation was observed between Tc-SPECT and FDG-PET imaging for calculation of EDV (r = 0.93), ESV (r = 0.93), LVEF (r = 0.83) and LVMM (r = 0.72). Conclusion: ECG-gated Tc-SPECT and FDG-PET using two tracers with different characteristics (perfusion versus metabolism) showed close agreement concerning measurements of left ventricular volumes, contractile function and myocardial mass by using a model-based analysis.

Summary Aim: We compared and delineated possible differences of model-based analysis of ECGgated SPECT using 99mTc-sestamibi (Tc- SPECT) with ECG-gated 18F-fluorodeoxyglucose- PET (FDG-PET) for determination of enddiastolic (EDV) and end-systolic (ESV) cardiac volumes, left ventricular ejection fraction (LVEF), and myocardial mass (LVMM). Patients, methods: 24 patients (21 men; age: 54 ± 12years) with coronary artery disease underwent Tc-SPECT and FDG-PET imaging for evaluation of myocardial perfusion and viability. By using model-based analysis EDV, ESV, LVEF and LVMM were calculated from short axis images of both Tc-SPECT and FDGPET. Results: Left ventricular volumes by Tc- SPECT and FDG-PET were 176 ± 60 ml and 181 ± 59 ml for EDV, and 97 ± 44 ml and 103 ± 45 ml for ESV respectively, LVEF was 47 ± 8% by Tc-SPECT and 45 ± 9% by FDG-PET. The LVMM was 214 ± 40 g (Tc-SPECT) and 202 ± 43 g (FDG-PET) (all p = NS, paired t-test). A significant correlation was observed between Tc-SPECT and FDG-PET imaging for calculation of EDV (r = 0.93), ESV (r = 0.93), LVEF (r = 0.83) and LVMM (r = 0.72). Conclusion: ECG-gated Tc-SPECT and FDG-PET using two tracers with different characteristics (perfusion versus metabolism) showed close agreement concerning measurements of left ventricular volumes, contractile function and myocardial mass by using a model-based analysis.

BACKGROUND AND PURPOSE: Computerized methods have been introduced for more objective quantification of angiographic occlusion rate and coil density as parameters of successful embolization. This study aimed 1) to evaluate this new computerized method for angiographic occlusion rating and coil density calculations by comparison with corresponding histometric parameters from retrieved human aneurysms, and 2) to compare the new computerized method with the present standard of subjective angiographic occlusion rating. MATERIALS AND METHODS: From 14 postmortem-retrieved human aneurysms, angiographic occlusion rate was determined by contrast medium attenuation-gradient distinction on digital subtraction angiographs after Guglielmi detachable coil (GDC) embolization. Angiographic coil density was calculated, approximating aneurysms as ellipsoid and coils as cylindric volumes. On surface-stained histologic ground sections of the respective aneurysms, the occluded aneurysm area and coil area were measured. Then, we calculated and compared the histometric occlusion rates and coil densities with the corresponding angiographic parameters by using the Wilcoxon paired signed-rank test and the Spearman rank correlation. RESULTS: Computerized angiographic occlusion rates (75%–100%) showed good correlation (r = 0.799; P < .01) with histometric occlusion-rates (61%–100%), resulting in no statistically significant differences (P = .2163). With 5.1% (±3.8), the mean difference between computerized angiographic occlusion rates and histometry was substantially lower compared with 10.7% (±8.7) mean difference between subjective angiographic estimations and histometry. Calculated angiographic coil density (13%–32%) significantly differed from histometric coil density (8%–35%; P < .05). CONCLUSIONS: For recanalized aneurysms, computerized angiographic occlusion rating showed better correspondence with histometry compared with subjective angiographic occlusion rating. Clinical application of this new tool may lead to more objective cutoff values for re-embolization indications. The value of coil density calculations seems limited by the approximation of the aneurysms as ellipsoid volumes.

UNLABELLED:The purpose of this study was to evaluate myocardial electrocardiography (ECG)-gated 13N-ammonia (13N-NH3) PET for the assessment of cardiac end-diastolic volume (EDV), cardiac end-systolic volume (ESV), left ventricular (LV) myocardial mass (LVMM), and LV ejection fraction (LVEF) with gated 18F-FDG PET as a reference method.METHODS:ECG-gated 13N-NH3 and 18F-FDG scans were performed for 27 patients (23 men and 4 women; mean+/-SD age, 55+/-15 y) for the evaluation of myocardial perfusion and viability. For both 13N-NH3 and 18F-FDG studies, a model-based image analysis tool was used to estimate endocardial and epicardial borders of the left ventricle on a set of short-axis images and to calculate values for EDV, ESV, LVEF, and LVMM.RESULTS:The LV volumes determined by 13N-NH3 and 18F-FDG were 108+/-60 mL and 106+/-63 mL for ESV and 175+/-71 mL and 169+/-73 mL for EDV, respectively. The LVEFs determined by 13N-NH3 and 18F-FDG were 42%+/-13% and 41%+/-13%, respectively. The LVMMs determined by 13N-NH3 and 18F-FDG were 179+/-40 g and 183+/-43 g, respectively. All P values were not significant, as determined by paired t tests. A significant correlation was observed between 13N-NH3 imaging and 18F-FDG imaging for the calculation of ESV (r=0.97, SEE=14.1, P<0.0001), EDV (r=0.98, SEE=15.4, P<0.0001), LVEF (r=0.9, SEE=5.6, P<0.0001), and LVMM (r=0.93, SEE=15.5, P<0.0001).CONCLUSION:Model-based analysis of ECG-gated 13N-NH3 PET images is accurate in determining LV volumes, LVMM, and LVEF. Therefore, ECG-gated 13N-NH3 can be used for the simultaneous assessment of myocardial perfusion, LV geometry, and contractile function.

The aim of this study was to evaluate the distribution of prostate cancer within the peripheral zone by prostate biopsies excluding the influence of the transition zone. A prospective, multicenter study was carried out using a consecutive series of men who underwent transrectal ultrasound guided prostate biopsies using different biopsy techniques at six institutions. Biopsies were directed strictly within the peripheral zone or strictly within the transition zone. A model of the peripheral zone with 18 sectors of similar volume was established and the biopsy cores obtained were associated with these sectors and analysed with respect to prostate cancer detection rate. A total of 904 men (mean age 66.8 years, range 42-86) with a median serum PSA of 8.1 ng/ml (2.2-940 ng/ml) entered the study. A total of 8,062 biopsy cores (mean 8.92/patient) were obtained. Each of the peripheral zone sectors tested by biopsies yielded a similar percentage of prostate cancer ( P=0.6). There was no increase in the incidence of cancer toward the lateral sectors compared to midline sectors ( P=0.53) of the peripheral zone. Biopsy sampling of the peripheral zone from the apex to the base yielded a similar percentage of prostate cancer ( P=0.47). Our data suggest that the distribution of cancer foci detected by biopsies in the peripheral zone of the prostate is homogeneous.

Putative precursors of endometrial cancer such as complex endometrial hyperplasia with atypia have been described to be monoclonal and considered to be genetically related. In order to identify a genetic marker that could serve as a putative predictor of endometrial cancer we analyzed 14 endometrial hyperplasia and 29 endometrial cancer samples for instabilities and loss of heterozygosity (LOH) in microsatellite sequences. Deletions on the short arm of chromosome 8 were frequently detected in both endometrial hyperplasia and cancer samples, suggesting that these deletions are early events in the development of endometrial cancer.

PURPOSE Vascular endothelial growth factor (VEGF) is a promotor for tumor angiogenesis, and is known to be elevated in breast and ovarian cancers. Through alternative splicing six VEGF isoforms were identified. We studied VEGF isoform expression in breast and ovarian cancer cell lines, as well as in breast carcinomas and ovarian tumors, and correlated the expression pattern with the in vitro invasiveness of the breast carcinoma cell lines and the clinicopathologic characteristics of the tumors. EXPERIMENTAL DESIGN Reverse transcription-PCR and automated laser fluorescence fragment analysis were used to determine the expression of each splice variant. This method allowed the detection of all of the splice variants simultaneously, especially VEGF145 for the first time in tumor tissue. RESULTS VEGF121 and VEGF165 were the most dominantly expressed variants in all of the tumor samples and cell lines investigated. VEGF145 was very weakly or not expressed in breast and ovarian cancers. Statistical analysis showed no correlation between VEGF splice variant expression in the tumors and histological type, differentiation grade, tumor size, Fédération Internationale des Gynaecologistes et Obstetristes, and nodal status from cancer patients. There was also no correlation between the invasive capacity of breast cell lines and VEGF isoform expression. CONCLUSIONS Even though expression levels of VEGF have been shown to be important for tumor invasion and progression, the present data indicate no relation of VEGF isoform pattern with invasion and progression.

The prevalence of coronary artery disease (CAD) is high in patients on renal replacement therapy; therefore, reliable noninvasive screening tests are needed. We retrospectively determined the sensitivity, specificity, and positive and negative likelihood ratios (LRs) for a history of chest pain, resting and exercise electrocardiography (ECG), thallium dipyridamole scintigraphy, and echocardiography in 42 patients undergoing chronic hemodialysis and 42 patients after renal transplantation who also underwent coronary angiography. In addition, the prognostic power of each test for the occurrence of a cardiovascular event after angiography (therapeutic intervention, myocardial infarction, or cardiovascular death) was evaluated during a follow-up of 37 months. Forty-three patients had significant CAD on angiography. Angina pectoris had a sensitivity of 65% and specificity of 66%, corresponding to a positive LR of 1.9 and a negative LR of 0.5. A variable number of patients underwent noninvasive tests before angiography. Results were similar in patients undergoing hemodialysis and after renal transplantation and in patients with or without angina pectoris. Exercise ECG could not be performed in the majority of patients, and resting ECG (sensitivity, 67%; specificity, 52%; corresponding to a positive LR of 1.4 and negative LR of 0.6) and scintigraphy (sensitivity, 80%; specificity, 37%; positive LR, 1.3; negative LR, 0.5) in patients on renal replacement therapy were not useful for the diagnosis of CAD. Angina also markedly increased the relative odds for the occurrence of a cardiovascular event during follow-up (relative odds, 4.6) compared with other noninvasive tests. Angina pectoris had the best informational and prognostic value of noninvasive screening methods, but angiography seems to be the only method to clearly document CAD in patients on renal replacement therapy.

The 4G/5G polymorphism of the plasminogen activator inhibitor type I (PAI-I) gene is involved in coronary artery disease (CAD), with the highest risk in 4G/4G homozygotes. The role of PAI-I polymorphism in patients suffering from CAD and history of sudden cardiac death (SCD) has not been addressed yet. We studied the frequency distribution of the PAI-I gene to test the hypothesis that the 4G/4G genotype favors myocardial ischemia and, even in the absence of acute infarction, promotes SCD in patients with CAD. Methods: The PAI-I 4G/5G genotypes and PAI-I antigen plasma levels were determined in 97 patients with CAD and a history of SCD treated with an implantable cardioverter defibrillator (ICD) (defibrillator group) comparing to 113 patients with CAD but no history of SCD (control group). Results: The defibrillator group consisted of significantly more 4G/4G homozygotes and higher PAI-I levels than the control group (44% vs. 24%, 173±41 vs. 144±49 ng/ml; P<.01). The carriers of 4G allele had a significantly higher risk for SCD (odds ratio (OR) 1.9) with the highest risk in the 4G/4G genotype (OR 3.6, P<.01). Conclusion: These results suggest that the PAI-I 4G/4G genotype is associated with SCD in patients suffering from CAD.

Objectives: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. Methods: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of <40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. Results: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p<0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p<0.001). The distribution of ACE and AT1 genotypes was not different between the two group. Conclusions: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.

This study determined the impact of clinical characteristics on shock occurrence and survival in patients with implantable cardioverter-defibrillator (ICD). Methods and Results: During a follow-up of 27 ± 18 months, the actuarial incidence of appropriate shocks in 200 consecutive patients was 18, 36 and 72% at 1, 3, and 5 years, respectively. Coronary artery disease was the only significant predictor for shock occurrence (relative risk 1.32, p = 0.03). The actuarial incidence of total mortality was 10, 17 and 33% at 1, 3, and 5 years, respectively. The most powerful predictors for total mortality were: New York Heart Association functional class (NYHA) III (relative risk 4.8, p = 0.001) and a history of congestive cardiac failure (relative risk 3.6, p = 0.01). Conclusion: During long-term follow-up, the majority of patients receive appropriate shocks. No strong predictors for shock occurrence can be identified from the data analyzed. A history of congestive cardiac failure and the NYHA III are the most powerful predictors for total mortality. These clinical factors may provide valuable criteria to identify patients who will benefit from the implantation of ICD.

The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.

In this study we investigated associations of the fibrinolytic parameters t-PA antigen and PAI-1 activity in 317 patients with angiographically proven coronary artery disease with gender, age classes, angiographic extent of disease, symptom class and history of myocardial infarction as clinical parameters, as well as with the established cardiovascular risk factors: smoking, arterial hypertension, cholesterol levels, triglyceride levels, obesity and diabetes mellitus, by use of univariate and multifactorial analysis, respectively. While PAI-1 activity was only associated with unstable angina, t-PA antigen was significantly associated with hypertriglyceridemia, unstable angina, and angiographic extent of disease.

After the Chernobyl accident Austria was among the countries with the highest radioactive fallout. In order to have a sufficient data base for further risk evaluation for the infant population, we monitored 131I and 134+137Cs (Na-scintillation detector and Germanium detector) in cow's milk (n=2347), human milk (n=238) and infant formula (n=118) longitudinally from 1986 to 1992. From these data and from average food consumption values, we calculated averago nucleid intake for hypothetical infants under different feeding regimens. Using previously published dose equivalent factors, we calculated the internal radiation doses for the infants. A hypothetical infant (breast or formula fed 0-12 months) born at the time of the event received 110 uSv until 1992 (30% was accumulated during the first year). If the infant was switched to cow's milk at 6 months of age, the accumulated cumulative dose was 195 uSv (50% was accumulated in the first year). A cow's milk fed infant who was 6 months of age at the time of the event received 675 uSv until 1092 (80% accumulated during the first year). An additional done of 675 uSv can result in adverse health effects. Thus, the countermeasures (avoidance of cow's milk) were effective in reducing the risk for infants.

There is limited information available on the vitamin K intake of lactating mothers, concentration of vitamin K1 in breast milk, and the effect of long-term vitamin K1 supplementation of lactating mothers on the vitamin K1 concentration in breast milk. In a randomized study, we followed 20 mothers who received a daily oral vitamin K1 supplement (average 88 micrograms, supplemented group) and 16 mothers receiving no supplement (control group) from 4 throughout 91 days postpartum. Maternal vitamin K intakes (weighed dietary intake) at 4-6, 25-29 and 87-91 days postpartum ranged between 73 and 1735 micrograms/day. Differences between the groups were statistically not significant. Average intake exceeded the recommended dietary intake for lactating women of 55 micrograms/day by 670%. In the supplemented group, mean breast-milk vitamin K1 concentrations (HPLC) at 5, 26 and 88 days postpartum were 1.73 (SD 0.74), 1.36 (SD 0.81) and 1.67 (SD 2.01) ng/ml, respectively. Corresponding values in the control group were 1.44 (SD 0.57), 1.68 (SD 0.70) and 1.78 (SD 1.05) ng/ml. The latter were not statistically different from values in the supplemented group. Mean daily vitamin K1 intakes of infants breast-fed by supplemented mothers were 0.69 (SD 0.42), 0.93 (SD 0.51) and 1.25 (1.53) micrograms, respectively on days 5, 26 and 88. Corresponding values in the control group were 0.69 (SD 0.30), 1.07 (SD 0.58) and 1.31 (SD 0.95) micrograms and were statistically not different from values in the supplemented group. Average vitamin K1 intakes corresponded to 7-13% of the recommended dietary intake of 10 micrograms/d for infants.(ABSTRACT TRUNCATED AT 250 WORDS)

SummaryFeeding of iron (Fe)‐fortified (12–15 mg/L) infant formulas is an effective and convenient means to protect infants from Fe deficiency. To study lower levels of Fe fortification of infant formulas (3 or 6 mg/L) compared with those currently in use, we compared Fe intake and Fe nutritional status of three groups of healthy, term infants between 90 and 274 days of age. One group received an Fe‐fortified whey‐predominant formula (3 mg/ L) and the second group received the same formula with a higher Fe level (6 mg/L). A comparison group was breast‐fed at least until 274 days of age. All infants received infant foods and cereals according to European Community recommendations. Mean Fe intake of infants fed formula fortified with 3 mg/L was significantly lower at 183 and 274 days of age (p < 0.05) than that of infants fed formula fortified with 6 mg/L. None of the infants fed the formula fortified with 3 mg/L met the recommended daily allowance value (10 mg) for infants between 6 and 12 months of age. Hemoglobin, hematocrit, mean corpuscular volume, free erythrocyte protoporphyrin, and serum ferritin levels were similar in the formula‐fed groups; none of the infants had depleted Fe stores (ferritin < 10 μg/L) at 183 and 274 days of age. Thirteen percent of breast‐fed infants had depleted Fe stores at 183 days of age, but only 3% were depleted at 273 days of age, when Fe‐fortified beikost was already part of the diet. No influence of Fe nutritional status was found on zinc and copper nutritional status or on growth. We conclude that regular consumption of an infant formula fortified with 3 mg Fe/L, a level substantially below present recommendations, prevents healthy, term infants from developing Fe deficiency during the first 6 months of life. It is preferable that infants 6 months of age and older receive an Fe‐fortified formula and a judicious selection of beikost to ensure an adequate dietary intake of Fe.