Comparison of high specific activity (-) and (+)-6-[18F]fluoronorepinephrine and 6-[18F]fluorodopamine in baboons: heart uptake, metabolism and the effect of desipramine

(-)-Norepinephrine is the principal neurotransmitter of the mammalian sympathetic nervous system and a major CNS neurotransmitter. The simple ring fluorinated derivatives of (-)- and (+)-norepinephrine [(-)- and (+)6-fluoronorepinephrine] and dopamine (6-fluorodopamine) have been labeled with 18F in high specific activity (2-5 Ci/mumol) and evaluated as tracers for (-)-norepinephrine. Comparative PET studies of (-) and (+)-6-[18F]fluoronorepinephrine [(-)-6-[18F]FNE and (+)-6-[18F]FNE] and 6-[18F]fluorodopamine (6-[18F]FDA) in the same baboon showed strikingly different kinetics in the heart. Analysis of plasma showed more rapid metabolism of 6-[18F]FDA with only 1%-2% of 18F remaining as parent tracer at 10 min after injection of 6-[18F]FDA, in contrast to 28% and 17% remaining after injection of (-) and (+)-6-[18F]FNE. No changes in vital signs were observed at any time during the study. Pretreatment with desipramine (0.5 mg/kg), a tricyclic antidepressant drug which interacts with a binding site associated with norepinephrine reuptake, markedly decreased cardiac uptake of 6-[18F]FDA and (-)-6-[18F]FNE. However, a greater blocking effect was observed for (-)-6-[18F]FNE. These studies show that (-) and (+)-6-[18F]FNE are similar to (-)- and (+)-norepinephrine in their patterns of metabolism and clearance in the heart and that (-)-6-[18F]FNE is a promising tracer for endogenous (-)-norepinephrine.     

Spurious associations in unreplicated selected lines

INTRODUCTION: Shocks during the vulnerable period of the cardiac cycle induce ventricular fibrillation (VF) if their strength is above the VF threshold (VFT) and less than the upper limit of vulnerability (ULV). However, the range of shock strengths that constitutes the vulnerable zone and the corresponding range of coupling intervals have not been defined in humans. The ULV has been proposed as a measure of defibrillation because it correlates with the defibrillation threshold (DFT), but the optimal coupling interval for identifying it is unknown. METHODS AND RESULTS: We studied 14 patients at implants of transvenous cardioverter defibrillators. The DFT was defined as the weakest shock that defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock that did not induce VF when given at 0, 20, and 40 msec before the peak of the T wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of 500 msec. The VFT was defined as the weakest shock that induced VF at any of the same four intervals. To identify the upper and lower boundaries of the vulnerable zone, we determined the shock strengths required to induce VF at all four intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT was 72 +/- 42 V, and the ULV was 411 +/- V. In all patients, a shock strength of 200 V exceeded the VFT and was less than the ULV. The coupling interval at the ULV was 19+/- 11 msec shorter than the coupling interval at the VFT (P < 0.001). The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at the VFT. A 20-msec error in the interval at which the ULV was measured could have resulted in underestimating it by a maximum of 95 +/- 31 V. The weakest shock that did not induce VF was greater for the shortest interval tested than for the longest interval at both the upper boundary (356 +/- 108 V vs 280 +/- 78 V; P < 0.01) and lower boundary (136 +/- 68 msec vs 100 +/- 65 msec; P < 0.05). CONCLUSIONS: The human vulnerable zone is not symmetric with respect to a single coupling interval, but slants from the upper left to lower right. Small differences in the coupling interval at which the ULV is determined or use of the coupling interval at the VFT to determine the ULV may result in significant variations in its measured value. An efficient strategy for inducing VF would begin by delivering a 200-V shock at a coupling interval 10 msec before the peak of the T wave.     

Developmental intrahepatic shunts of childhood: radiological features and management

The purpose of this study was to evaluate the role of radiological techniques in the diagnosis and management of developmental intrahepatic shunts. Hepatic vascular fistulae are recognised sequelae of liver trauma and intrahepatic tumours. However, there are rare developmental malformations which may present in childhood or later life and which may carry life-threatening complications. Retrospective analysis of clinical and radiological data was carried out in 24 patients. Anomalies evaluated were: (a) direct communication between hepatic artery and hepatic veins; (b) congenital hepatoportal arteriovenous malformations; and (c) congenital portocaval anastomosis with persistent flow through the ductus venosus. Although rare, the prompt recognition of these vascular anomalies allows early surgical or radiological intervention and reversal of the haemodynamic complications.     

Nurses'' logs as an evaluation tool for school-based violence prevention programs

AIM: To develop a reliable, machine-readable coding system for dental appliances. METHODS: Incorporation of two-dimensional bar codes and matrix codes into a range of dental appliances using printed thermal substrates and laser-etched ceramic discs. RESULTS: Problems including reaction of thermal substrates with methyl methacrylate monomer, loss of code clarity, limited areas available for bar codes, difficulty in scanning opaque pigmented acrylic resin and palatal and lingual surfaces were overcome using 4 mm2 data matrix codes etched onto ceramic discs. CONCLUSIONS: Reliable automatic identification of dental appliances was achieved using laser-etched matrix codes. Further development is necessary in relation to optimisation of code size, encryption, scanners and maintenance of code readability over time.     

Parotid cancer

This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) for baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p = 0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reasons for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.     

A broad-spectrum microbicide with virucidal activity against sexually transmitted viruses

Sodium dodecyl sulfate (SDS), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. In preliminary experiments, we demonstrated that SDS is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. We hypothesized that SDS might be capable of denaturing the capsid proteins of nonenveloped viruses. In this report, we demonstrate inactivation of rabbit, bovine, and human papillomaviruses after brief treatment with dilute solutions of SDS. Effective concentrations were nontoxic to rabbit skin and to split-thickness grafts of human foreskin epithelium. This is the first report of a microbicidal surfactant that will inactivate papillomaviruses. We propose that SDS is now a candidate microbicide for formulation and testing with humans.     

Systemic and translesional activation of coagulation, fibrinolytic, and inhibitory systems in candidates for coronary angioplasty: basal state and effect of successful dilation

OBJECTIVES: Thrombosis is a major contributor to complications associated with coronary interventions. It is unclear whether patients who have undergone angioplasty are predisposed to thrombus formation because of underlying perturbations in their hemostatic equilibrium. METHODS: Concentration or activity was measured for 14 plasma proteins involved in the coagulation, fibrinolytic, and inhibitory systems. Baseline systemic measurements were compared between patients undergoing balloon angioplasty (n = 15) and normal subjects (n = 32), with sampling repeated at the end of the procedure. To better assess the local hemostatic environment near the site of dilation, intracoronary arterial samples were also obtained just proximal and distal to the dilated stenosis. RESULTS: Multiple differences in measured coagulation proteins were found at baseline between the angioplasty candidates and control subjects, including higher mean concentration of plasma fibrinogen (P <.001) and lower high-molecular-weight kininogen concentration (P <.01) and factor XII activity (P <.01). Concentrations of the inhibitory proteins antithrombin III and protein S also differed significantly (P <.001 and P <.01, respectively), with a trend toward lower protein C concentration as well (P <.05). Finally, heightened fibrinolysis was suggested by a marked increase in mean plasma d-dimer concentration in the angioplasty candidates (293 +/- 191 ng/mL vs 116 +/- 31 ng/mL, P <.01), with a more modest increase in tissue plasminogen activator (P <.05) and decrease in alpha2-antiplasmin (P <.001). Importantly, none of the parameters obtained during the procedure differed significantly from samples obtained before and after angioplasty, and no translesional gradients were observed. CONCLUSIONS: Patients with active ischemic syndromes who are considered candidates for coronary angioplasty demonstrate significant and multiple alterations in their coagulation, inhibitory, and fibrinolytic systems. However, no further changes were observed during coronary dilation, either systemically or locally, after pretreatment with typical doses of heparin and aspirin.     

Congestion control of packet-switched networks with three types of input buffer limits

Congestion in a store-and-forward data communications network manifests itself by a rapid degradation of network throughput and a fast increase in the average transit delay. A study of a congestion control mechanism in a packet-switched data network is presented. Buffer limits are placed on the input, transit and exit packets in each switching node. By a judicious choice of the buffer limits, it is shown that the network throughput can be maintained at a constant level, while the average transit delay remains within acceptable bounds for offered loads beyond the congestion point.