Whole-body FDG PET/CT is more accurate than conventional imaging for staging primary breast cancer patients.

PURPOSE: This retrospective study aimed (1) to compare the diagnostic accuracy of whole-body FDG PET/CT for initial breast cancer staging with the accuracy of a conventional, multimodal imaging algorithm, and (2) to assess potential alteration in patient management based on the FDG PET/CT findings. METHODS: Patients with primary breast cancer (106 women, mean age 57 ± 13 years) underwent whole-body FDG PET/CT and conventional imaging (X-ray mammography, MR mammography, chest plain radiography, bone scintigraphy and breast, axillary and liver ultrasonography). The diagnostic accuracies of FDG PET/CT and a conventional algorithm were compared. Diagnostic accuracy was assessed in terms of primary tumour detection rate, correct assessment of primary lesion focality, T stage and the detection rates for lymph node and distant metastases. Histopathology, imaging or clinical follow-up served as the standards of reference. RESULTS: FDG PET/CT was significantly more accurate for detecting axillary lymph node and distant metastases (p = 0.0125 and p < 0.005, respectively). No significant differences were detected for other parameters. Synchronous tumours or locoregional extraaxillary lymph node or distant metastases were detected in 14 patients (13%) solely by FDG PET/CT. Management of 15 patients (14%) was altered based on the FDG PET/CT findings, including 3 patients with axillary lymph node metastases, 5 patients with extraaxillary lymph node metastases, 4 patients with distant metastases and 3 patients with synchronous malignancies. CONCLUSION: Full-dose, intravenous contrast-enhanced FDG PET/CT was more accurate than conventional imaging for initial breast cancer staging due to the higher detection rate of metastases and synchronous tumours, although the study had several limitations including a retrospective design, a possible selection bias and a relevant false-positive rate for the detection of axillary lymph node metastases. FDG PET/CT resulted in a change of treatment in a substantial proportion of patients.

[Modern CT and PET/CT imaging of the liver]. / Moderne CT- und PET/CT-Bildgebung der Leber.

Computed tomography (CT) is now widely available and represents an important and rapid method for the diagnostics of acute liver disease, characterization of focal liver lesions, planning of interventional therapy measures and postintervention control. In recent years CT has not become less important despite the increasing value of magnetic resonance imaging (MRI). By the use of different contrast medium phases good characterization of space-occupying lesions can be achieved. For the diagnostics of hepatocellular carcinoma (HCC) a triphasic examination protocol should always be implemented. The introduction of dual energy CT increased the sensitivity of imaging of hypervascularized and hypovascularized liver lesions and by the use of virtual native imaging it has become possible to avoid additional native imaging which reduces the x-ray exposition of patients. Positron emission tomography (PET) has an advantage for imaging in oncology because nearly the complete body of the patient can be screened and this is the main indication for PET/CT (whole-body staging). For purely hepatic problems 18F-fluorodeoxyglucose (FDG)-PET/CT using diagnostic CT data has a higher precision than CT alone but is inferior to MRI.

Safety of resveratrol with examples for high purity, trans-resveratrol, resVida(®).

Studies with resVida(®) (a high purity trans-resveratrol) show that trans-resveratrol is a substance of low oral toxicity. An acceptable daily intake (ADI) in food of 450 mg/day has been defined, a level well beyond natural dietary intake of trans-resveratrol. The ADI was based on no-observed-adverse-effect-levels (NOAELs) of 750 mg/kg bw/day in 13-week developmental toxicity studies by the dietary route and a standard safety margin of 100. In studies by gavage, the kidney and bladder are target organs at very high dosages (2,000-3,000 mg/kg bw/day). Six-month studies in rat and rabbit models show no significant increase in toxicity in comparison to 4-week studies. Lower quoted NOAELs in gavage studies (ca. 300 mg/kg bw/day) potentially reflect more rapid bioavailability, but different dosage regimes complicate comparisons. Short-term studies show no genotoxicity in vivo. A 6-month mouse carcinogenicity model showed no increase in tumors. Clinical data support an ADI of at least 450 mg/day, and kinetic data from the DSM 13-week toxicity study also support the expectation of no increase in toxicity with longer term intake.

Repeated oral once daily intake of increasing doses of the novel synthetic genistein product Bonistein in healthy volunteers.

Bonistein is a new product consisting of > 99.5 % synthetic genistein, an isoflavone with phyto-oestrogenic properties, which might be a safe and efficacious alternative for the prevention of post-menopausal bone loss to the traditional hormone replacement therapy. A randomised, open-labelled and sequential-group phase I study was performed to assess safety, tolerability and pharmacokinetic characteristics of oral administrations of Bonistein. Thirty healthy volunteers received in three subsequent groups 30, 60 or 120 mg once daily for 14 days. For the pharmacokinetic profiles of Bonistein, blood samples were taken on study Days 1 (after first dose) and 14 (steady state). Repeated intake of Bonistein was well tolerated. A total of 33 adverse events were reported, mainly of mild intensity. No relevant changes in clinical laboratory or vital signs were observed. The pharmacokinetic characteristics of Bonistein revealed comparable results for extent and rate of absorption on Days 1 and 14. Both AUC and C (max) values of Bonistein increased in proportion with the dose.

Relationship between lower limb dynamics and knee joint pain.

To test the hypothesis that appropriate and timely neuromuscular control of limb motions plays an important role in the preservation of joint health, we kinematically and kinetically examined the behavior of the legs of young adult subjects at heel strike during natural walking. We compared a group of 18 volunteers, who, we presumed, were preosteoarthrotic because of mild, intermittent, activity-related knee joint pain, with 14 age-matched asymptomatic normal subjects. The two groups of subjects exhibited similar gait patterns with equivalent cadences, walking speeds, terminal stance phase knee flexion, maximum (peak) swing angular velocity, and overall shape of the vertical ground reaction. However, our instrumentation detected statistically significant differences between the two groups within a few milliseconds of heel strike. In the knee pain group, the heel hit the floor with a stronger impact in this brief interval. Just before heel strike, there was a faster downward velocity of the ankle with a larger angular velocity of the shank. The follow-through of the leg immediately after heel strike was more violent with larger peak axial and angular accelerations of the leg echoed by a more rapid rise of the ground reaction force. This sequence of events represents repetitive impulsive loading, which consistently provoked osteoarthrosis in animal experiments. We refer to this micro-incoordination of neuromuscular control not visible to the naked eye as "microklutziness."

Effects of retinacular release and tibial tubercle elevation in patellofemoral degenerative joint disease.

Release of the patellar retinaculum and tibial tubercle elevation have both been advocated for the treatment of patellofemoral degeneration. Questions remain, however, regarding the magnitude and predictability of such effects in diseased joints. Using cadaver knee joints exhibiting a range of patellofemoral cartilage degeneration, we investigated the effects on joint contact pressures on release of the patellar retinaculum, followed by tibial tubercle elevations of 1.25 and 2.5 cm. Retinacular release failed to alter the joint-loading parameters significantly. Tibial tubercle elevation reduced the patello-femoral joint contact area and contact force, but failed to cause a consistent change in contact pressure. Tibial tubercle elevation also caused a migration of the joint contact area superolaterally on the retropatellar surface. This migration occurred in conjunction with ventral tilting of the inferior pole of the patella as the tubercle was elevated, suggesting that significant changes in joint kinematics may result from this procedure.

Effect of oxygen withdrawal on active and passive electrical properties of arterially perfused rabbit ventricular muscle.

Oxygen withdrawal from myocardial cells leads to changes of the transmembrane action potential (mainly action potential shortening), to cellular uncoupling, and to changes of vascular permeability. This study was aimed at the simultaneous measurement of electrical activity and passive electrical properties (extracellular and intracellular longitudinal resistance) in arterially perfused rabbit papillary muscles under different conditions of changed oxygen supply. These included 1) complete anoxia (erythrocyte-free perfusate), 2) hypoxia (PO2 between 23-28 mm Hg, erythrocytes present) in the presence and absence of glucose, and 3) normoxia with erythrocyte-free perfusate. Similarly to myocardial ischemia, rapid cellular uncoupling occurred only after an initial stable period of approximately 17 minutes, and it required complete anoxia. The marked shortening of the action potential developed before cellular uncoupling. In six out of eight experiments, the fibers were inexcitable when uncoupling started. In severe hypoxia, no significant change of internal longitudinal resistance was observed over 35-40 minutes. The time course of the extracellular longitudinal resistance was different from the change in intracellular resistance: A marked decrease occurred almost immediately after the onset of oxygen withdrawal. This decrease was followed by a small increase in conduction velocity, which was most likely due to a change in the interstitial compartment (edema). It was observed during anoxic as well as during hypoxic perfusion. We conclude that 1) cellular uncoupling in arterially perfused tissue requires almost complete oxygen lack and occurs with a delay of more than 10 minutes, 2) marked action potential shortening precedes uncoupling, and therefore can not simply be attributed to an increase in free, intracellular calcium, and 3) vascular endothelial function is more sensitive to oxygen withdrawal than the myocyte.

Anatomy of the ankle and foot.

The ankle and foot complex at times must be mobile and at other times must be quite stable. The bony, ligamentous, and muscular structures of the ankle and foot are presented with respect to their mobility and stability functions. Innervation and vascular supply are discussed. Normal anatomy provides a basis and a reference point for discussion of dysfunction of the ankle and foot.

Extracellular K+ and H+ shifts in early ischemia: mechanisms and relation to changes in impulse propagation.

Heart and skeletal muscle cells rapidly lose potassium ions after withdrawal of oxygen. In myocardial ischemia, cellular release of potassium and interruption of extracellular washout produce a rapid and marked increase of extracellular K+ concentration. Harris et al. were the first to observe the coincidence of the K+ shift and the frequent occurrence of ventricular arrhythmias. They ascribed a major role to K+ in the genesis of the electrophysiological changes in early ischemia. The purpose of this article is to outline briefly in the first part the relationship between potassium accumulation and the electrical changes in ischemia with emphasis on reviewing the role of K+ in the slowing of impulse propagation and production of conduction block. In the second part, the possible mechanisms leading to potassium imbalance will be discussed and experimental data will be presented which suggest that an important component of net potassium loss is related to the development of acidosis.

Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle.

Extracellular and intracellular longitudinal resistances (ro and ri), transmembrane potentials, and conduction velocity were determined in arterially blood-perfused rabbit papillary muscles. Cable analysis was made possible by placing the muscle in a H2O-saturated gaseous environment, which acted as an electrical insulator. Ischemia was produced by exchanging the O2 in the atmosphere by N2 (94% N2-6% CO2) in addition to arresting coronary flow. The first 10-15 minutes of ischemia were characterized by an increase in ro, while ri remained constant. The early part of the increase in ro coincided with the drop in perfusion pressure and was probably due to the diminution of intravascular volume. Rapid electrical uncoupling, reflected by an increase in ri (threefold within 5 minutes), occurred thereafter. The dissociation between the early increase in ro and the delayed increase in ri produced an initial increase in the ratio ro:ri, which subsequently decreased. The decrease in conduction velocity was less than observed in intact hearts with ischemia. This difference is explained by the relatively small changes in resting membrane potential and action potential amplitude in the preparation used. Our results suggest that in the early, reversible phase of ischemia, the increase in ro contributes to a small but significant extent to the slowing of conduction. After 15-20 minutes, the rapid cellular uncoupling, which was most likely coincident with breakdown of cellular homeostasis, may contribute to the occurrence of arrhythmias during this phase of ischemia. Moreover, the early change in the ratio ro:ri will influence the amplitude of the extracellular electrograms following coronary occlusion (TQ-segment and ST-segment shifts).

Electrical constants of arterially perfused rabbit papillary muscle.

1. Right ventricular rabbit papillary muscles were arterially perfused with a mixture of Tyrode solution, bovine erythrocytes, dextran and albumin. In the recording chamber, they were surrounded by a H2O-saturated atmosphere of O2 and CO2 which served as an electrical insulator. 2. Conduction velocity and passive electrical properties were determined from intra- and extracellular potentials measured during excitation and during flow of subthreshold current. 3. The propagation of the action potential was linear along the muscle at a velocity of 55.6 cm/s. The extracellular wave-front voltage was 51.5 mV. 4. The following values for passive cable properties were obtained: (i) a ratio of extra- to intracellular longitudinal resistance of 1.2; (ii) an extracellular specific resistance (Ro) of 63 omega cm; (iii) an intracellular specific resistance (Ri) of 166 omega cm; (iv) a space constant lambda of 0.357 mm; (v) a membrane time constant tau of 2.57 ms. The space constant lambda* recalculated for zero extracellular resistance was 0.528 mm. 5. Arresting perfusion with drop of perfusion pressure was associated with an immediate increase of the extracellular longitudinal resistance by 35% and a decrease of conduction velocity by 13%. 6. The present results demonstrate the important contribution of the extracellular resistance to electrotonic interaction and propagation in densely packed myocardial tissue. Moreover, changes in perfusion pressure are associated with changes in extracellular resistance, probably as a consequence of changes in intravascular volume.

Effects of a calcium entry promoting 1,4,5,7-tetrahydro-furo[3,4-b] pyridine derivative on Na+-, Ca2+- and Mg2+-dependent bioelectrical activity of Purkinje fibres and papillary muscles.

4-(2-Difluoromethoxyphenyl)-2-methyl-5-oxo-1,4,5,7-tetrahydro- furo[3,4-b]pyridine-3-carboxylic acid ether ester (CGP 28 392), a dihydropyridine derivative with an annellated lactone ring, was examined in automatically discharging calf Purkinje fibres. Velocity of spontaneous depolarization during both the early and the late phase of the diastolic pause and the rate of rise of the action potential were increased, with the threshold potential at which the upstroke is generated being unaltered. These findings are discussed in terms of ionic mechanisms, including in particular the contribution of sodium ions during the late phase of the diastolic depolarization and the novel type of calcium channel which is supposed to contribute to pacemaker depolarization and action potential initiation. In general, the effects of equimolar concentrations of nifedipine were opposite to those of CGP 28 392. At 1 X 10(-5) mol/l, however, both CGP 28 392 and nifedipine accelerated the late phase of diastolic depolarization. In electrically stimulated, partially depolarized guinea-pig papillary muscles, CGP 28 392 also prolonged the slow action potential and markedly increased inotropism. In equimolar concentrations nifedipine shortened the slow action potential and inhibited contractility. The effects of CGP 28 392 are thus compatible with facilitation of calcium entry and--in Purkinje fibres--also with enhancement of fast sodium conductivity.