Fluorodeoxyglucose uptake in dysfunctional myocardium subtended by an occluded coronary artery

Background. Myocardial segments with impaired function may have the potential for functional recovery. Augmented exogenous glucose uptake in relation to blood flow estimated by [2-18F]2-fluorodeoxyglucose (FDG) and positron emission tomography (PET) frequently indicates functional reversibility. The spectrum of FDG uptake levels in relation to Sestamibi uptake and dobutamine contraction reserve in areas with impaired function subtended by an occluded coronary artery has never been reported. Methods and results. Seventeen patients with stable angina pectoris and dysfunctional myocardium subtended by an occluded coronary artery were studied with FDG-PET, low-dose dobutamine echocardiography and Sestamibi - Single Photon Emission Computerized Tomography. In a 16 segment model dysfunctional myocardial segments showed a normally distributed FDG uptake ranging from 34% to 150% when normalized to peak segmental Sestamibi uptake. Low FDG uptake was associated with both lack of dobutamine induced contractile reserve and low Sestamibi uptake (in 73% of the segments) whereas high FDG uptake displayed both contractile reserve and Sestamibi uptake (57%). Segments with intermediate FDG uptake had either contractile reserve or a preserved Sestamibi uptake (62%). Conclusion. Dysfunctional myocardium subtended by an occluded coronary artery represents a continuum of metabolic states with a high degree of heterogeneity with regard to contractile reserve and Sestamibi uptake.     

Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark

To explore prenatal risk factors that are common to testicular cancer and cryptorchidism, two parallel case-control studies were conducted in Denmark. Information about characteristics of the mother, the pregnancy, and the birth were obtained from the mothers of cases and controls, using a mailed self-administered questionnaire. A maternal age above 30 years was associated with odds ratios (OR) of 1.9 (95 percent confidence interval [CI]= 1.2-3.0) for cryptorchidism and 2.0 (CI = 1.2-3.6) for testicular seminoma; the latter effect was particularly high when the boy was the first child of the mother (OR = 4.1, CI = 1.1-14.6). Birth weights below 3,000 g or above4,000 g were associated with increased risks of testicular cancer, with OR sup to 2.6 (CI = 1.1-5.9) for birth weight below 2,500 g. For cryptorchidism, there was a monotonous trend in the OR from 0.4 in birth weights above 4,500 g to 2.3 in birth weights below 2,500 g. The association between cryptorchidism and testicular cancer was not attenuated by adjustment for maternal age and birthweight, indicating that all three variables are independent risk factors for testicular cancer. With the exception of high maternal age, which consistently is associated more strongly with seminoma than withnon-seminoma, it remains most likely that seminoma and non-seminoma have similar causes. This revised version was published online in July 2006 with corrections to the Cover Date.     

Fluorodeoxyglucose uptake in dysfunctional myocardium subtended by an occluded coronary artery

Background. Myocardial segments with impaired function may have the potential for functional recovery. Augmented exogenous glucose uptake in relation to blood flow estimated by [2-18F]2-fluorodeoxyglucose (FDG) and positron emission tomography (PET) frequently indicates functional reversibility. The spectrum of FDG uptake levels in relation to Sestamibi uptake and dobutamine contraction reserve in areas with impaired function subtended by an occluded coronary artery has never been reported. Methods and results. Seventeen patients with stable angina pectoris and dysfunctional myocardium subtended by an occluded coronary artery were studied with FDG-PET, low-dose dobutamine echocardiography and Sestamibi - Single Photon Emission Computerized Tomography. In a 16 segment model dysfunctional myocardial segments showed a normally distributed FDG uptake ranging from 34% to 150% when normalized to peak segmental Sestamibi uptake. Low FDG uptake was associated with both lack of dobutamine induced contractile reserve and low Sestamibi uptake (in 73% of the segments) whereas high FDG uptake displayed both contractile reserve and Sestamibi uptake (57%). Segments with intermediate FDG uptake had either contractile reserve or a preserved Sestamibi uptake (62%). Conclusion. Dysfunctional myocardium subtended by an occluded coronary artery represents a continuum of metabolic states with a high degree of heterogeneity with regard to contractile reserve and Sestamibi uptake.     

No prediction of recurrence of meningiomas by PCNA and Ki-67 immunohistochemistry

Immunohistochemistry for the expression of the proliferation markersproliferating cell nuclear antigen (PCNA) and Ki-67 wasstudied in 16 non recurring meningiomas, 11 meningiomasrecurring as benign tumors, 6 recurring as atypicalmeningiomas and in 9 recurring as malignant meningiomas.Non recurring meningiomas were defined in this studyas tumors without recurrence at least 8 yearsafter surgery. In addition 16 benign recurrences, 14atypical- and 12 malignant meningiomas were studied. Ineach group great variation of labeling indices (LI)= per cent of tumor cells labeled wasobserved, especially of PCNA LIs. The non recurringmeningiomas displayed lower mean LI for PCNA andKi-67 than did the recurring meningiomas of allgroups but the differences were not statistically significant.The same pattern was seen when totally resectedtumors were studied alone. Benign-, atypical-, and malignantmeningiomas had labeling indices that were related tothe grade of malignancy. Only PCNA LIs ofatypical- and malignant meningiomas were statistically significantly higherthan PCNA LIs of non recurring meningiomas. Thestudy indicates that PCNA and Ki-67 are ofminor value as predictors of recurrence of benignmeningiomas.     

Chemical Stability of Insulin. 1. Hydrolytic Degradation During Storage of Pharmaceutical Preparations

Hydrolysis of insulin has been studied during storage of various preparations at different temperatures. Insulin deteriorates rapidly in acid solutions due to extensive deamidation at residue Asn^A21. In neutral formulations deamidation takes place at residue Asn^B3 at a substantially reduced rate under formation of a mixture of isoAsp and Asp derivatives. The rate of hydrolysis at B3 is independent of the strength of the preparation, and in most cases the species of insulin, but varies with storage temperature and formulation. Total transformation at B3 is considerably reduced when insulin is in the crystalline as compared to the amorphous or soluble state, indicating that formation of the rate-limiting cyclic imide decreases when the flexibility of the tertiary structure is reduced. Neutral solutions containing phenol showed reduced deamidation probably because of a stabilizing effect of phenol on the tertiary structure (-helix formation) around the deamidating residue, resulting in a reduced probability for formation of the intermediate imide. The ratio of isoAsp/Asp derivative was independent of time and temperature, suggesting a pathway involving only intermediate imide formation, without any direct side-chain hydrolysis. However, increasing formation of Asp relative to isoAsp derivative was observed with decreasing flexibility of the insulin three-dimensional structure in the formulation. In certain crystalline suspensions a cleavage of the peptide bond A8–A9 was observed. Formation of this split product is species dependent: bovine > porcine > human insulin. The hydrolytic cleavage of the peptide backbone takes place only in preparations containing rhombohedral crystals in addition to free zinc ions.To whom correspondence should be addressed at Nove Research Institute, Novo Alle, DK-2880Bagsvaerd, Denmark