Mapping the SF-12 to the EuroQol EQ-5D Index in a national US sample.

BACKGROUND: Preference scores for the Medical Outcomes Study (MOS) SF-12 would enable its use in cost-effectiveness analyses. Previous mapping studies of MOS instruments top reference-based instruments have not examined performance in national samples. PARTICIPANTS: 15,000 adults in the 2000 Medical Expenditure Panel Survey annual survey including the SF-12 and EQ-5D Index. METHODS: Regression of the EQ-5D Index scores onto the physical and mental component summary scores of the SF-12, testing 2nd-4th degree polynomial and spline models, including and excluding sociodemographics. RESULTS: A 2nd degree polynomial model explained 63% of the variance in EQ-5D scores, with robust internal and external validation. More complex mod-els explained minimally additional variance. Compared with EQ-5D valuations, prediction models overestimated the lowest health states (6% of the population). CONCLUSIONS: The mapped SF-12 yields usable preference-scaled scores, with some caution for the lowest health states.     

An exploration of relative health stock in advanced cancer patients.

OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions.     

Over the rainbow: advancing child health in the new millennium.

Research studies presented at the annual Pediatric Academic Societies meeting provide continued evidence of the impact of the environment on child health, the prevalence of mental health problems in children and adolescents, and the benefits of comprehensive health care coverage. Other studies report on the efficacy of new formats for delivering pediatric health care and the content of health supervision visits, and identify potential solutions for existing deficits and disparities in health care delivery. Despite this abundance of positive studies, the United States continues to lag behind many developed countries in its broader adoption of effective strategies such as universal health coverage. Child health care professionals must continue to speak out on behalf of the needs of infants, children, and adolescents and work for systemic change in health care delivery.     

Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima–media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.
Methods: The common carotid artery intima–media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women).
Results: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706±211 µm and 749±395 µm, respectively) compared with that of the control population (614±113 µm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima–media thickening greater than 1.2 mm.
Conclusion: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.     

Effects of phencyclidine on acoustic startle and prepulse inhibition in neuronal nitric oxide synthase deficient mice.

Prepulse inhibition of acoustic startle is a behavioural response, which is used to estimate sensorimotor gating deficits in schizophrenia. Recent studies show that several behavioural effects of the psychotomimetic drug, phencyclidine (PCP), in rodents are blocked by nitric oxide synthase (NOS) inhibitors suggesting that NO plays an important role in the pharmacological effects of PCP. The present study was conducted to examine the effects of PCP on prepulse inhibition in neuronal NOS (nNOS) deficient mice. PCP treatment caused a significant and dose-related increase in prepulse inhibition in nNOS-/- mice whereas prepulse inhibition was not significantly affected in +/+ and +/- mice. Basal prepulse inhibition level did not differ significantly between the groups. Furthermore, PCP caused a dose-related decrease in startle response reactivity in +/+ mice but did not significantly affect this measure in +/- and -/- mice. Basal startle response level did not differ between +/+ and +/- but was significantly lower in -/- mice. It is concluded that nNOS plays a role in the NO-sensitive effects of PCP.     

Redox-sensitive signaling factors as a novel molecular targets for cancer therapy.

Tumor cells undergoing proliferation, de-differentiation and progression depend on a complex set of respiratory pathways to generate the necessary energy. The metabolites from these pathways produce significant oxidative stress and must be buffered to prevent permanent cell damage and cell death. It is now clear that, in order to cope with and defend against the detrimental effects of oxidative stress, a series of redox-sensitive, pro-survival signaling pathways and factors regulate a complex intracellular redox buffering network. This review develops the hypothesis that tumor cells use these redox-sensitive, pro-survival signaling pathways and factors - up-regulated due to increased tumor cell respiration - to evade the damaging and cytotoxic effects of specific anticancer agents. It further suggests that redox-sensitive, signaling factors may be potential novel targets for drug discovery.     

Inhibition of rat liver CYP2D in vitro and after 1-day and long-term exposure to neuroleptics in vivo-possible involvement of different mechanisms.

The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the activity of rat CYP2D measured as a rate of ethylmorphine O-deethylation. The reaction was studied in control liver microsomes in the presence of neuroleptics, as well as in microsomes of rats treated intraperitoneally (i.p.) for 1-day or 2-weeks (twice a day) with pharmacological doses of the drugs (promazine, levomepromazine, thioridazine, perazine 10 mg kg(-1); chlorpromazine 3 mg kg(-1); haloperidol 0.3 mg kg(-1); risperidone 0.1 mg kg(-1); sertindole 0.05 mg kg(-1)), in the absence of the neuroleptics in vitro. Neuroleptics added in vitro to control liver microsomes decreased the activity of the rat CYP2D by competitive or mixed inhibition of the enzyme. Thioridazine (Ki=15 microM) was the most potent inhibitor of the rat CYP2D among the drugs studied, whose effect was more pronounced than that of the other neuroleptics tested: phenothiazines (Ki=18-23 microM), haloperidol (Ki=32 microM), sertindole (Ki=51 microM) or risperidone (Ki=165 microM). The investigated neuroleptics-when given to rats in vivo-also seemed to exert an inhibitory effect on CYP2D via other mechanisms. One-day exposure of rats to the classic neuroleptics decreased the activity of CYP2D in rat liver microsomes. After chronic treatment with the investigated neuroleptics, the decreased CYP2D activity produced by the phenothiazines was still maintained, while that caused by haloperidol diminished. Moreover, risperidone decreased the activity of that enzyme. The obtained results indicate drug- and time-dependent interactions between the investigated neuroleptics and the CYP2D subfamily of rat cytochrome P-450, which may proceed via different mechanisms: (1) competitive or mixed inhibition of CYP2D shown in vitro, the inhibitory effects of phenothiazines being stronger than those of haloperidol or atypical neuroleptics, but weaker than the effects of the respective drugs on human CYP2D6; (2) in vivo inhibition of CYP2D, produced by both 1-day and chronic treatment with phenothiazines, which suggests inactivation of enzyme by intermediate metabolites; (3) in vivo inhibition of CYP2D by risperidone, produced only by chronic treatment with the drug, which suggests its influence on the enzyme regulation.     

Mass spectrometric and high performance liquid chromatography profiling of the venom of the Brazilian vermivorous mollusk Conus regius: feeding behavior and identification of one novel conotoxin.

Carnivorous mollusks belonging to the genus Conus paralyze their prey by injecting a rich mixture of biologically active peptides. Conus regius is a vermivorous member of this genus that inhabits Brazilian tropical waters. Inter-, intra-species and individual variations of cone snail venom have been previously reported. In order to investigate intra-specific differences in C. regius venom, its feeding behavior and the correlation between these two factors, animals were pooled according to gender, size and season of collection, and their venom composition was compared by high performance liquid chromatography (HPLC). Both the whole venom and one specific peak were monitored by HPLC. Chromatographic profiles revealed no significant differences in their peak areas, indicating that the venom composition, based solely in the presence or absence of the major peaks, is stable regardless of season, gender and size. Therefore, analysis of one given toxin, eluting in one of the major peaks, is representative among the population. Moreover, this work presents the identification of one novel conotoxin (rg11a), which amino acid sequence was deduced by mass spectrometry.     

New drugs of 2004.

OBJECTIVES: To provide information regarding the most important properties of the new therapeutic agents marketed in 2004. DATA SOURCES: Product labeling supplemented selectively with published studies and drug information reference sources. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA SYNTHESIS: The 22 new therapeutic agents marketed in the United States during 2004 are reviewed in this article. Indications and information on dosage and administration for these agents are reviewed, as are the most important pharmacokinetic properties, adverse events, drug interactions, and other precautions. Practical considerations for the use of the new agents are also discussed. When possible, the properties of the new drugs are compared with those of older drugs marketed for the same indications. CONCLUSION: A number of the new therapeutic agents marketed in 2004 have important advantages over older medications. An understanding of the properties of these agents is important for the pharmacist to effectively counsel patients about their use and to serve as a valuable source of information for other health professionals regarding these drugs.