Detection of moderate and severe coronary artery stenosis with technetium-99m tetrofosmin myocardial single-photon emission tomography

The aim of this study was to determine the diagnostic accuracy of technetium-99m tetrofosmin myocardial imaging for the localization of coronary artery stenoses of different degrees of severity. Stress-rest single-photon emission tomography (SPET) was performed on separate days in 80 patients (64 males, 16 females; mean age 61 years; 43 patients with previous myocardial infarction; 18 patients with pharmacological stress), within 6 months of coronary angiography. Scintigraphic images were blindly and independently evaluated by three observers. Coronary stenosis was defined as a >50% narrowing in luminal diameter; severe stenosis was defined as a proximal stenosis of >75% or a peripheral stenosis of >90%. Coronary angiography revealed normal coronary arteries or insignificant coronary stenosis in 13 patients and significant coronary stenoses in 67 patients. The sensitivity and specificity of ^99mTc-tetrofosmin SPET in respect of severely stenosed vessels were, respectively, 80% and 65% for the left anterior descending artery (LAD), 100% and 46% for the right coronary artery (RCA) and 58 and 78% for the left circumflex artery (LCx) territories. Considering all the significantly stenosed vessels, a significant decrease in sensitivity was observed for LAD territories (to 59%, P=0.05), and a nonsignificant decrease for RCA (88%) and LCx (47%) territories while specificity values remained essentially unchanged. No significant changes in sensitivity or specificity were observed when regions with previous myocardial infarction were excluded. In conclusion, the sensitivity of ^99mTc-tetrofosmin SPET for the localization of individual stenosed vessels is only moderate when all significant stenoses are considered, but the ability of this technique to predict the location of severe coronary artery stenoses seems satisfactory, with the exception of the low specificity in respect of RCA territories. Received 26 April and in revised form 7 June 1997     

Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance.

OBJECTIVE: To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance. RESEARCH DESIGN AND METHODS: We enrolled 180 pregnant Caucasian women with positive diabetic screening. All women underwent a 3-h 100-g oral glucose tolerance test (OGTT) at 27th +/- 4 week of gestation. At the time of OGTT, we measured: fasting plasma glucose, fasting lipids profile and determined ApoE polymorphisms to evaluate the effects on lipid levels. In 83 women with normal glucose tolerance and at term delivery we evaluated the association between maternal serum TG, specific maternal parameters known to affect fetal growth and newborn weight. RESULTS: Based on OGTT, gestational diabetes mellitus (GDM) was diagnosed in 36 women (20%), impaired glucose tolerance (IGT) in 23 (13%), and normal glucose tolerance (NGT) in 121 (67%). Serum TG concentration was significantly higher in women with GDM (2.47 +/- 0.77 mmol/l) as compared with NGT (1.99 +/- 0.64 mmol/l) or IGT (1.98 +/- 0.81 mmol/l) (P < 0.01). ApoE3 allelic frequency was 86%, ApoE2 and ApoE4 were 5 and 9%, respectively. We found no clear-cut association between apoE genotype and serum TG concentration. Macrosomia and LGA newborns were more frequent in IGT than in GDM or NGT (P < 0.01). In the 83 women with positive diabetic screening but normal glucose tolerance who delivered at term, the incidence of LGA infants was significantly higher in those with TG levels higher than the 75th percentile (> 2.30 mmol/l) (21%) than in mothers who had normal TG levels (4.5%) (P < 0.05). Pre-pregnancy BMI (r(2) = 0.067), weight gain during pregnancy (r(2) = 0.062), fasting serum TG (r(2) = 0.09), and 2-h post-OGTT glucose levels (r(2) = 0.044) were all associated with neonatal body weight (all P < 0.05 or less). However, on a multiple regression analysis, only pre-pregnancy BMI (F-test = 7.26, P < 0.01), and fasting serum TG (F-test = 4.07, P < 0.01) were independently associated with birth weight. CONCLUSIONS: Pre-pregnancy BMI and fasting maternal serum TG determined in the last trimester of gestation were independently associated with neonatal birth weight in women with normal glucose tolerance, but positive screening test. TG levels measured in the third trimester of pregnancy are independent of the genetic polymorphism of ApoE.     

Cellular bases of the antitumor activity of the novel taxane IDN 5109 (BAY59-8862) on hormone-refractory prostate cancer.

Taxane-based therapies appear to have a significant efficacy in clinical trials on hormone-refractory prostate carcinoma. In the present study, we investigated the cellular response of androgen-independent prostate carcinoma cell lines to the novel taxane IDN 5109 (BAY 59-8862) and evaluated its antitumor activity. In previous preclinical studies, this new paclitaxel (PTX) analogue was characterized by high tolerability and antitumor efficacy, ability to overcome multidrug resistance, and activity by oral administration. Upon treatment, DU145 and PC3 prostate carcinoma cell lines underwent a transient mitotic arrest. This was followed by G1 arrest and rapid occurrence of apoptosis in DU145 cells, whereas in PC3 cells, which are defective for the postmitotic checkpoint, a slow cell death was preceded by DNA endoreduplication. At the biochemical level, such events were associated with tubulin polymerization, activation of the mitosis-promoting factor, and phosphorylation of Bcl-X(L)/Bcl-2/Raf-1. In addition, IDN 5109 shared with PTX the ability to down-regulate the expression of the two potent angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor. These findings indicated that IDN 5109 affected the same pathways involved in the cellular response to PTX and suggested that an antiangiogenic effect mediated by inhibition of paracrine stimulation of endothelial cells might contribute to the antitumor effect of both drugs. In in vivo experiments, the new taxane displayed a superior and more persistent effect compared with PTX against DU145 tumor xenografts. Such an effect was associated with pronounced reduction of the tumor microvessel density, superior to that achieved by PTX. These results support a potential therapeutic advantage of IDN 5109 over PTX against hormone-refractory prostate carcinoma.     

Cell cycle checkpoint efficiency and cellular response to paclitaxel in prostate cancer cells

BACKGROUND: Defects in the cell cycle machinery of prostate cancer cells might impair the efficiency of cell cycle checkpoints and affect the cell response to chemotherapeutic drugs. We examined the relationship between the status of microtubule damage-activated checkpoints and the response of hormone-refractory prostate cancer cells to paclitaxel. METHODS: The two cell lines DU145 and PC3 harboring defects at proteins involved in the regulation of checkpoints activated by microtubule damage were examined for cell sensitivity, apoptotic response, and efficiency of checkpoints in response to paclitaxel. RESULTS: In spite of a comparable sensitivity to the antiproliferative effects of paclitaxel, DU145 and PC3 cells exhibited different cell cycle control at checkpoints activated by microtubule damage. A transient mitotic arrest was induced by the taxane in both cell lines. However, PC3 cells underwent a rapid mitotic slippage and displayed a defective postmitotic checkpoint as evidenced by the appearance of polyploid cells. In this cell line, paclitaxel-induced cell death was a slow and delayed event, occurring also after S-phase re-entry. The mitotic checkpoint appeared to be more stringent in DU145 cells compared to PC3 cells. Moreover, despite the expression of mutated proteins involved in the prevention of DNA endoreduplication (p53, pRb, and p16(INK4A)), these cells did not progress into the cell cycle but efficiently underwent apoptosis by 24 hr. Such a response of DU145 cells was associated with phosphorylation of the p21(WAF1) protein. CONCLUSIONS: These observations evidence that activation of checkpoints following microtubule damage in prostate cancer may be regulated through complex mechanisms possibly involving p21(WAF1). Our findings support that the status of cell cycle checkpoints might affect the modality of cell death. However, the relevance of the mode of cell death for the sensitivity to taxanes remains to be determined.     

Plasma lipids and lipoproteins pattern in beta-thalassemia major

We studied serum lipids and lipoproteins in 20 patients with beta-thalassemia major, under high transfusion programme and regular chelation therapy, and in 20 control subjects. Total cholesterol, HDL-cholesterol, HDL2-and HDL3-cholesterol, apolipoprotein A and B levels were significantly lower in patients with Cooley's anemia, whereas free cholesterol, triglycerides and the HDL-/HDL3-cholesterol ratio did not differ in the two groups. We think that liver damage plays an important role in determining the altered lipoprotein pattern in beta-thalassemia major. However, other factors may contribute to cause such lipid changes.     

Performance characteristics obtained for a new 3-dimensional lutetium oxyorthosilicate-based whole-body PET/CT scanner with the National Electrical Manufacturers Association NU 2-2001 standard.

This article reports the results of performance measurements obtained for the lutetium oxyorthosilicate (LSO)-based whole-body PET/CT scanner Biograph 16 HI-REZ with the National Electrical Manufacturers Association (NEMA) NU 2-2001 standard. The Biograph 16 HI-REZ combines a multislice (16-slice) spiral CT scanner with a PET scanner composed of 24.336 LSO crystals arranged in 39 rings. The crystal dimensions are 4.0x4.0x20 mm3, and the crystals are organized in 13x13 blocks coupled to 4 photomultiplier tubes each. The 39 rings allow the acquisition of 81 images 2.0 mm thick, covering an axial field of view of 162 mm. The low- and high-energy thresholds are set to 425 and 650 keV, respectively, acquiring data within a 4.5-ns-wide coincidence window. METHODS: Performance measurements for the LSO-based PET/CT scanner were obtained with the NEMA NU 2-2001 standard, taking into account issues deriving from the presence of intrinsic radiation. RESULTS: The results obtained with the NEMA NU 2-2001 standard measurements were as follows: average transverse and axial spatial resolutions (full width at half maximum) at 1 cm and at 10 cm off axis of 4.61 (5.10) mm and 5.34 (5.91) mm, respectively; average sensitivity of 4.92 counts per second per kilobecquerel for the 2 radial positions (0 and 10 cm); 34.1% system scatter fraction; and peak noise equivalent count (NEC) rates of 84.77 kilocounts per second (kcps) at 28.73 kBq/mL (k=1 in the NEC formula; noiseless random correction) and 58.71 kcps at 21.62 kBq/mL (k=2; noisy random correction). CONCLUSION: The new integrated PET/CT system Biograph 16 HI-REZ has good overall performance, with, in particular, a high resolution, a low scatter fraction, and a very good NEC response.