Pegylated liposomal doxorubicin plus highly active antiretroviral therapy versus highly active antiretroviral therapy alone in HIV patients with Kaposi's sarcoma

Twenty-eight HIV patients either naive or failing highly active antiretroviral therapy (HAART)with moderate-advanced Kaposi's sarcoma (KS)were randomly chosen to initiate a new HAART regimen plus pegylated liposomal doxorubicin(PLD) or the new HAART regimen alone. After 48 weeks, better response rates were observed in the HAART plus PLD group (76% versus 20%).In HIV-infected patients with moderate-advanced KS, HAART alone may not be enough for KS response.     

Novel insight into the detailed myocardial motion and deformation of the rodent heart using high-resolution phase contrast cardiovascular magnetic resonance

Background

Phase contrast velocimetry cardiovascular magnetic resonance (PC-CMR) is a powerful and versatile tool allowing assessment of in vivo motion of the myocardium. However, PC-CMR is sensitive to motion related artifacts causing errors that are geometrically systematic, rendering regional analysis of myocardial function challenging. The objective of this study was to establish an optimized PC-CMR method able to provide novel insight in the complex regional motion and strain of the rodent myocardium, and provide a proof-of-concept in normal and diseased rat hearts with higher temporal and spatial resolution than previously reported.

Methods

A PC-CMR protocol optimized for assessing the motion and deformation of the myocardium in rats with high spatiotemporal resolution was established, and ten animals with different degree of cardiac dysfunction underwent examination and served as proof-of-concept. Global and regional myocardial velocities and circumferential strain were calculated, and the results were compared to five control animals. Furthermore, the global strain measurements were validated against speckle-tracking echocardiography, and inter- and intrastudy variability of the protocol were evaluated.

Results

The presented method allows assessment of regional myocardial function in rats with high level of detail; temporal resolution was 3.2 ms, and analysis was done using 32 circumferential segments. In the dysfunctional hearts, global and regional function were distinctly altered, including reduced global peak values, increased regional heterogeneity and increased index of dyssynchrony. Strain derived from the PC-CMR data was in excellent agreement with echocardiography (r = 0.95, p < 0.001; limits-of-agreement −0.02 ± 3.92%strain), and intra- and interstudy variability were low for both velocity and strain (limits-of-agreement, radial motion: 0.01 ± 0.32 cm/s and −0.06 ± 0.75 cm/s; circumferential strain: -0.16 ± 0.89%strain and −0.71 ± 1.67%strain, for intra- and interstudy, respectively).

Conclusion

We demonstrate, for the first time, that PC-CMR enables high-resolution evaluation of in vivo circumferential strain in addition to myocardial motion of the rat heart. In combination with the superior geometric robustness of CMR, this ultimately provides a tool for longitudinal studies of regional function in rodents with high level of detail.     

The DIRE score: predicting outcomes of opioid prescribing for chronic pain.

The objective of this retrospective study was to test the validity and reliability of a scoring tool (the DIRE Score), for use by clinicians, that predicts which chronic noncancer pain patients will have effective analgesia and be compliant with long-term opioid maintenance treatment. DIRE scores were assigned to 61 cases from the pain center's databases. These cases were abstracted into vignettes that were reviewed and scored by 6 physicians. Repeat scoring was carried out on a subset of 30 vignettes after 2 weeks. The main outcome measures were: global impression of compliance and efficacy as indicated in the medical record and by interview with the patient's treating clinician; and final disposition, ie, whether or not opioids were continued or discontinued at the time of last clinical documentation. Internal consistency of the factors making up the DIRE Score was high (Cronbach's alpha = .80). Sensitivity and specificity of the DIRE Score for predicting patient compliance were 94% and 87%, respectively. For efficacy, sensitivity and specificity were 81% and 76%. For disposition, the sensitivity and specificity were 86% and 73%. Intraclass correlation was 0.94 for interrater reliability and 0.95 for intrarater reliability. PERSPECTIVE: Public controversy about the use of long-term opioids for chronic pain fuels physician ambivalence about the prescribing process. In this initial retrospective study, validity and reliability of the DIRE Score are demonstrated. The score correlated well with measures of patient compliance and efficacy of long-term opioid therapy.     

A Primary Male Autosomal Linkage Map of the Horse Genome

A primary male autosomal linkage map of the domestic horse (Equus caballus) has been developed by segregation analysis of 140 genetic markers within eight half-sib families. The family material comprised four Standardbred trotters and four Icelandic horses, with a total of 263 offspring. The marker set included 121 microsatellite markers, eight protein polymorphisms, five RFLPs, three blood group polymorphisms, two PCR–RFLPs, and one single strand conformation polymorphism (SSCP). One hundred markers were arranged into 25 linkage groups, 22 of which could be assigned physically to 18 different chromosomes (ECA1, ECA2, ECA3, ECA4, ECA5, ECA6, ECA7, ECA9, ECA10, ECA11, ECA13, ECA15, ECA16, ECA18, ECA19, ECA21, ECA22, and ECA30). The average distance between linked markers was 12.6 cM and the longest linkage group measured 103 cM. The total map distance contained within linkage groups was 679 cM. If the distances covered outside the ends of linkage groups and by unlinked markers were included, it was estimated that the marker set covered at least 1500 cM, that is, at least 50% of the genome. A comparison of the relationship between genetic and physical distances in anchored linkage groups gave ratios of 0.5–0.8 cM per Mb of DNA. This would suggest that the total male recombinational distance in the horse is 2000 cM; this value is lower than that suggested by chiasma counts. The present map should provide an important framework for future genome mapping in the horse.     

Lesions of basolateral amygdala impair extinction of CS motivational value,but not of explicit conditioned responses,in Pavlovian appetitive second-order conditioning

The basolateral amygdala (BLA) is important for the modification of the motivational significance of events through associative learning. In previous work, we found that BLA was critical for the acquisition of conditioned reinforcement value to a visual conditioned stimulus (CS) paired with food. Unlike normal rats, rats with neurotoxic lesions of the BLA failed to acquire Pavlovian second-order conditioning to an auditory stimulus paired with the first-order visual CS in the absence of food. In this experiment, we examined the role of BLA in the extinction of the previously acquired conditioned reinforcement value of a Pavlovian CS. Rats received first-order visual CS-food pairings prior to either BLA- or sham-lesions. Subsequent CS-alone extinction training reduced the ability of the visual CS to reinforce second-order conditioning of an auditory stimulus in the sham-lesioned rats, but not in the BLA-lesioned rats. Despite this persistence of the conditioned reinforcement value of the visual first-order CS in the BLA-lesioned rats, no effects of the lesions were observed on extinction of the explicit behavioural conditioned responses elicited by that CS.     

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23

Objective: Iron isomaltoside (Monofer^®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA.

Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000?mg of iron isomaltoside infused in single doses up to 2000?mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters.

Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500?mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0?g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found.

Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000?mg and cumulative doses up to 3000?mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.     

A community action programme for reducing harmful drinking behaviour among adolescents: the Trelleborg Project

AIMS: To evaluate a 3-year community intervention programme by measuring changes in drinking patterns in a 15-16-year-old population. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: The action programme included five demand-reducing and one supply-reducing interventions. Cross-sectional, non-repeated data were collected from a questionnaire distributed in classrooms from 1999 to 2001 and 2003 (n = 1376, 724 boys and 652 girls; response rate = 92.3%). Stepwise logistic regression analyses were used to determine the relationship between different risk factors and excessive drinking, heavy episodic drinking, purchaser of alcohol and alcohol provided by parents. The results from the intervention community were also compared with similar Swedish cross-sectional data sets. FINDINGS: The results of our analyses indicated a decrease in harmful drinking behaviour in Trelleborg when comparing baseline with postintervention measurements. The comparison with other studies showed that the changes in these indicators were more rapid and consistent in Trelleborg. Finally, the multivariable logistic regression analyses showed that the outcomes were not likely to be attributed to changes in environmental factors. CONCLUSIONS: We concluded that a community action programme based on the systems approach reduced hazardous alcohol consumption effectively among adolescents in Trelleborg.