Soluble TNF receptors in amniotic fluid and in urine from pregnant women.

Secretion of soluble cytokine receptors has been suggested as a mechanism for regulation of cytokine activity in vivo. The present investigation was performed to study whether secretion of soluble TNF (tumor necrosis factor) receptors (TNFRs) might be associated with pregnancy. There are two known molecular species of the TNFR, the 55-kDa TNFR and the 75-kDa TNFR. The 75-kDa, as well as the 55-kDa TNFR, was detected in urine from pregnant women, whereas only the 75-kDa TNFR was detected in urine from the non-pregnant group. The concentration of TNFRs in urine increased towards term and was reduced in association with spontaneous delivery. The soluble forms of both TNFRs were also detected in amniotic fluid. Collectively, the data suggest that secretion of soluble TNFRs during pregnancy might be a defence mechanism for the protection of the fetus against TNF action.     

The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs

Patients on antiepileptic drugs (AEDs) may have elevated levels of plasma total homocysteine (p-tHcy). The aim of this study was to assess the effect of B-vitamin supplementation on the levels of p-tHcy and markers of endothelial activation and lipid peroxidation. A total of 33 adult patients on AEDs were identified with either fasting (Group 1, n=23) or post methionine load (PML) (Group 2, n=10) hyperhomocysteinemia. Subjects were supplemented with B-vitamins for 30 days: folic acid 0.4 mg, pyridoxine 120 mg and riboflavin 75 mg per day. After supplementation, serum folate and pyridoxal phosphate had increased, while fasting and PML p-tHcy had decreased (P<0.0001) by 36 and 26%, respectively. Prior to supplementation, the Group 1 patients had elevated levels of P-selectin and von Willebrand factor (vWF) (P=0.05 and 0.03, respectively). After supplementation, the levels of intercellular cell adhesion molecules had decreased (P=0.01) and E-selectin decreased nonsignificantly (P=0.07). However, the levels of vascular cell adhesion molecules had increased (P<0.0001), while lipid peroxidation were unchanged. In conclusion, the combined supplementation with folic acid, pyridoxine and riboflavin reduced fasting and PML hyperhomocysteinemia in patients on AEDs. Patients with fasting hyperhomocysteinemia had elevated levels of P-selectin and vWF, which may indicate an increased risk of cardiovascular disease. Furthermore, B-vitamin supplementation influenced endothelial activation, although the clinical implication is uncertain.     

In vitro agreement between magnetic resonance imaging and intraluminal Doppler ultrasound for high flow velocity measurements

OBJECTIVE: Differences of opinion in the literature about the agreement between magnetic resonance imaging (MRI) and ultrasound Doppler (USD) for high blood velocity measurement were the basis for this investigation. It compares in vitro velocity measurements by MRI with intraluminal USD, using a specially designed flow phantom. DESIGN: The flow phantom consisted of a pulsatile pump, tubing, a prosthetic heart valve, measurement sections and a reservoir. Peak systolic velocities (0.7-5.0 m/s, n = 10) were measured with standard MRI phase shift velocity mapping using different regions of interest (ROIs). Intravascular USD velocity measurements were carried out using a thin cannula measuring peak systolic local maximum and local mean velocity within the small sample volume. RESULTS: Using maximum velocity USD recordings, comparison with MRI velocities was poor when the ROI covered the complete vessel lumen giving offset -22.3% and limits of agreement (LOA) 57.5 and 105.1%. When the ROI was small the velocities were closer with offset -11.8% and LOA 75.3-103.3%. When the spatial resolution was comparable and the spatial mean was read from the USD recordings, the velocities showed good agreement with an offset close to zero (0.45%). CONCLUSION: This study shows the importance of selecting small ROIs when using MRI for evaluating valve stenosis. Only when using spatially mean velocities over comparable regions the two methods showed good agreement.     

Effect of diethylstilbestrol and estramustine phosphate (estracyt®) on delayed hypersensitivity response to oxazolone in male mice

The effects of diethylstilbestrol (DES) and estramustine phosphate (EMP) on delayed hypersensitivity response (DTH) to oxazolone in male mice were investigated using a radioisotopic ear method. DES significantly inhibited the ability to express a DTH response and was most effective when given during the effector phase of the reaction. EMP had no effects when the animals were exposed to the drug during the effector phase, while it resulted in a strong and dose-dependent depression of the DTH response when applied in the sensitization phase. Possible involvement of suppressor cells was investigated by pretreatment of animals with cyclophosphamide or by adoptive transfer of tentative suppressor cells from spleen, lymph nodes, or peritoneal cavity. However, no evidence of cellular or humoral suppressor factors induced by drug treatment was found.     

Moment-to-moment dynamics of ADHD behaviour

Background  

The behaviour of children with Attention-Deficit / Hyperactivity Disorder is often described as highly variable, in addition to being hyperactive, impulsive and inattentive. One reason might be that they do not acquire complete and functional sequences of behaviour. The dynamic developmental theory of ADHD proposes that reinforcement and extinction processes are inefficient because of hypofunctioning dopamine systems, resulting in a narrower time window for associating antecedent stimuli and behaviour with its consequences. One effect of this may be that the learning of behavioural sequences is delayed, and that only short behavioural sequences are acquired in ADHD. The present study investigated acquisition of response sequences in the behaviour of children with ADHD.     

Behavioral effects of intra-cranial self-stimulation in an animal model of attention-deficit/hyperactivity disorder (ADHD)

Attention deficit/hyperactivity disorder (ADHD), characterized by inappropriate levels of activity, attention, and impulsivity, has been suggested to be caused by changes in reinforcement and extinction processes possibly linked to dysfunctioning dopamine systems. The present study investigated reinforcement processes in spontaneously hypertensive rats (SHR), an animal model of ADHD. Using intra-cranial self-stimulation (ICSS), behavioral effects of varying current intensity, reinforcer density, and reinforcer delay were tested. Current was varied in order to find the weakest current producing the maximal response rate (optimal current) in the SHR and the controls during high (120 reinforcers/min) and low reinforcer densities (1 reinforcer/min). The results showed that optimal current was significantly lower in the SHR than in the controls during high reinforcer density while maximal response rates were not significantly different. During low reinforcer density, optimal current was not significantly different in the two strains, but maximal response rate was significantly higher in the SHR than in the controls. The SHR produced more responses during the testing of reinforcer density, but changes in reinforcer density affected response rates similarly in the two strains. The decrease in response rate as a function of reinforcer delay was more pronounced in the SHR than in the controls. Overall, more responses with short inter-response times (IRT) were found in the SHR compared to the controls during intermittent reinforcement. The results are consistent with a steepened delay-of-reinforcement gradient in SHR.     

Effects of delayed reinforcers on the behavior of an animal model of attention-deficit/hyperactivity disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD), affecting 3-5% of grade-school children, is a behavioral disorder characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity. It has been suggested that the symptoms are caused by altered reinforcement and extinction processes, behaviorally described as an abnormally short and steep delay-of-reinforcement gradient in ADHD. The present study tested predictions from the suggested shortened and steepened delay gradient in ADHD in an animal model, the spontaneously hypertensive rats (SHRs). It was predicted that SHR responding during baseline would mainly consist of responses with short inter-response times, and that responding would be more rapidly reduced in the SHR than in the controls by the introduction of a time interval between the response and reinforcer delivery. Effects of a resetting delay of reinforcement procedure with water as the reinforcer were tested on two baseline reinforcement schedules: variable interval 30 s (VI 30 s) and conjoint variable interval 60 s differential reinforcement of high rate 1s (VI 60 s DRH 1 s). The results showed a higher rate of responses in the SHR than in the controls during baseline, mainly consisting of responses with short inter-response times. The statistical analyses showed that response rates decreased more rapidly as a function of reinforcer delay in the SHR than in the controls. The analyses of the estimates of the reinforcer decay parameter showed no strain differences during the VI 30 s schedule but showed a significant strain difference at the end, but not at the start, of the sessions during the VI 60 s DRH 1 s schedule. In general, the results support predictions from the suggested steepened delay gradient in SHR. However, the predictions were only partly confirmed by the analyses of the decay parameter.     

Weekly one-hour paclitaxel as first-line chemotherapy for metastatic breast cancer

In this first reported study of weekly paclitaxel administered as first-line chemotherapy for metastatic breast cancer, paclitaxel 100 mg/m² was administered in a 1-h infusion on a weekly basis to 35 patients who may previously have received adjuvant chemotherapy (but not taxane-containing regimens), but not for advanced or metastatic disease. A median of 14 infusions per patient was given at a mean delivered dose intensity of 94 mg/m² per week. In 33 assessable patients, a complete response (CR) was observed in 1 patient and partial responses (PRs) in 12 patients, producing an overall response rate of 40%. Stable disease (SD) was observed in 17 patients, of whom 9 were stabilized for more than 24 weeks. Thus, clinical benefit (CR+PR+SD_{≥24 weeks}) was observed in 67% of the patients. Time to progression was 189 days, the duration of response 180 days and overall survival 544 days. Five patients developed grade 3 neutropenia and five patients grade 3 neurotoxicity. Thus, this study has shown that weekly paclitaxel as first-line therapy for metastatic or advanced breast cancer produces comparable response rates and less toxicity than when the drug is given every three weeks.     

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo

Rationale The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered.Objective This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo.Methods Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers (n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo.Results Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response.Conclusions Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.