Assessment of quality of life in children with peanut allergy

Children with a peanut allergy (PA) are faced with food and social restrictions due to the potentially life-threatening nature of their disease, for which there is no cure or treatment. This inevitably impacts upon their quality of life (QoL). QoL of 20 children with PA and 20 children with insulin-dependent diabetes mellitus (IDDM) was measured using two disease-specific QoL questionnaires (higher scores correspond to a poorer QoL). One questionnaire was designed by us and the other was adapted from the Vespid Allergy QoL questionnaire. We gave subjects cameras to record how their QoL is affected over a 24-h period. Response rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA and IDDM subjects, respectively. Children with a PA reported a poorer quality of life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40 for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (p≤0.001) in questionnaire 2. PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home. Photographs fell into seven common categories: food, management, environment, away from home, physical activities, restaurant and people. Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions. PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants. The QoL in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans.     

The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.     

Stimulus functions of drugs and the assessment of abuse liability

The development of a unifying framework for conceptualizing the commonalities in various forms of substance abuse must encompass the data base focused upon the stimulus functions of drugs. In the first instance, for example, the research on drug self-administration has provided convincing evidence of a remarkable concordance between laboratory animals and human substance abusers in the reinforcing stimulus functions of a range of chemical agents. The recognition of these cross-species and cross-drug generalities has radically changed conceptualizations of substance abuse from a reactive to a more active process and has encouraged the kind of functional analysis of drug-seeking and drug-taking that has proven productive and useful in the study of other behavioral interactions. In this regard as well, recent refinements in the analysis of the discriminative stimulus functions of drugs have provided a more comprehensive basis for characterizing a chemical agent's spectrum of action and evaluating its abuse liability. While the correlation between the discriminative stimulus functions and the reinforcing stimulus functions is remarkably high for some drug classes, there are notable exceptions. Finally, the assessment of abuse liability requires an analysis of the eliciting stimulus functions of drugs as reflected by the physiological and behavioral changes, both acute and chronic, that follow drug administration. The methods used to evaluate both physiological dependence and behavioral toxicity in relationship to sensory and motor effects for a range of abused drugs have depended heavily upon an assessment of the eliciting stimulus functions of such compounds.     

Patterns of Cocaine Use Among Cocaine-Dependent Outpatients

The authors systematically evaluated the frequency patterns of cocaine use in 85 cocaine-dependent outpatients and found four patterns of use: continuous (27%), intermittent patterned (35%), intermittent nonpatterned (25%), and occasional (13%). Few subjects reported consistent cycling between binges and crashes. There were no significant differences in patterns of use associated with gender, race, educational level, route of administration, or recency of heroin use. Continuous users and occasional users were older than intermittent users. Because different contingencies may control patterned vs. nonpatterned cocaine use, pattern of use may have implications for treatment, even in individuals reporting similar amounts of cocaine use.     

Acute psychoses: A proposed diagnosis for ICD-11 and DSM-V

This paper concerns the diagnostic classification of nonaffective acute remitting psychosis (NARP), which we also term acute brief psychosis. We argue that NARP can be delineated from both schizophrenia and the affective psychoses and considered as a single diagnosis. As indicated by the term NARP, four criteria would be central to the diagnosis: 1. nonaffective, 2. acute onset (over less than two weeks), 3. recovery within a brief duration (less than six months), and 4. psychosis broadly defined. We review the rationale and the empirical evidence for this proposed classification.     

Regulation of COX-2 mediates acid-induced bone calcium efflux in vitro.

Chronic metabolic acidosis induces net Ca efflux from bone; this osteoclastic bone resorption is mediated by increased osteoblastic prostaglandin synthesis. Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is present in both constitutive (COX-1) and inducible (COX-2) forms. We report here that acidosis increases both osteoblastic RNA and protein levels for COX-2 and that genetic deficiency or pharmacologic inhibition of COX-2 significantly reduces acid-induced Ca efflux from bone. INTRODUCTION: Incubation of neonatal mouse calvariae in medium simulating physiologic metabolic acidosis induces an increase in osteoblastic prostaglandin E2 (PGE2) release and net calcium (Ca) efflux from bone. Increased PGE2 is necessary for acid-induced bone resorption, because inhibition of cyclooxygenase activity with indomethacin significantly decreases not only PGE2 production but also Ca release. Cyclooxygenase is present in both constitutive (COX-1) and inducible (COX-2) forms. Because COX-2 activity has been implicated in several forms of pathological bone resorption, we tested the hypothesis that COX-2 is critical for acid-induced, cell-mediated bone Ca efflux. MATERIALS AND METHODS: To determine the effect of metabolic acidosis on COX-2 RNA and protein, primary cells isolated from neonatal CD-1 mouse calvariae were cultured in neutral (Ntl) or physiologically acidic medium (Met). RNA levels for COX-2 and COX-1 were measured by quantitative real-time PCR. Levels of COX-2 and COX-1 protein were measured by immunoblot analysis. To determine the effect of acidosis on bone Ca efflux in genetically deficient COX-2 mice, mice heterozygous for the COX-2 knockout (strain B6;129S7-Ptgs2(tm1Jed)/J) were used as breeders, and neonatal calvariae were cultured in Ntl or Met. To determine the effects of the specific COX-2 inhibitor, NS398, on acid-induced bone resorption, CD-1 calvariae were incubated in Ntl or Met with or without NS398 (1 microM). Medium PGE2 was assayed by ELISA. RESULTS: Incubation of mouse calvarial cells in Met significantly increased COX-2 RNA and protein levels without a change in COX-1. Increased COX-2 protein levels in response to Met were also observed in cultured calvariae. Acid-induced, cell-mediated Ca efflux from B6;129S7-Ptgs2(tm1Jed)/J calvariae was dependent on genotype. From 0 to 24 h, when physicochemical Ca efflux predominates, Met significantly increased net Ca efflux in all genotypes. After 24 h, when cell-mediated Ca efflux predominates, Met induced greater Ca efflux from (+/+) than from (+/-), and there was no increase from (-/-). In calvariae from CD-1 mice, NS398 significantly inhibited both the acid-induced increase in PGE2 and Ca release. CONCLUSIONS: The specific acid-induced increase in COX-2 RNA and protein levels and the dependency of the increased Ca efflux on COX-2 activity, as determined by both genetic deficiency and pharmacologic inhibition, show that COX-2 is critical for acid-induced, cell-mediated bone resorption.     

Familial stenosis of the pulmonary artery branches with a JAG1 mutation.

Although most congenital heart defects are isolated abnormalities of embryonic development, with little genetic contribution, a small number are components of syndromes. In such cases, an accurate diagnosis has important implications for individual prognosis and familial genetic counseling. Alagille syndrome (AGS) is a dominantly inherited multisystem developmental disorder, which primarily affects the liver, heart, eyes, skeleton, and face. In recent years, the identification of the AGS gene has drawn attention to the existence of subclinical carriers, and broadened the spectrum of phenotypical variation associated with this syndrome. The authors present a case of mother and son with benign stenosis of the pulmonary artery branches. Subtle facial aspects suggested the diagnosis of AGS, which was confirmed by molecular analysis. Relevant clinical investigations and diagnostic implications are discussed.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Intrauterine position affects motoneuron number and muscle size in a sexually dimorphic neuromuscular system

The intrauterine position occupied by a rodent fetus influences the amount of testosterone to which it is exposed before birth. Animals that are gestated between two male fetuses (2M) are exposed to higher circulating levels of testosterone than are animals positioned between two female fetuses (2F) and there are reliable differences in the reproductive physiology and behavior of 2M and 2F animals when adult. To determine whether intrauterine position modifies development of the central nervous system, we examined the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) in male and female gerbils from known intrauterine positions. We found that adult 2M female gerbils had 16% more SNB motoneurons than did 2F females. 2M males did not differ from 2F males in SNB motoneuron number, but the bulbocavernosus muscle, which is innervated by SNB motoneurons, was approximately 50% larger in 2M than in 2F males. These data indicate that intrauterine position can influence the morphology of the sexually dimorphic SNB neuromuscular system.     

Characteristics of placebo response during long-term treatment of panic disorder

Mixed-panic disorder patients (16/60, 27%) randomly assigned to receive blind placebo during a 40-week treatment study were defined as placebo responders based on combined criteria of Hamilton Anxiety Scale score percentage decreases below the median point (-42%), moderate to marked improvement on both clinician and patient Clinical Global Impressions scores, and panic-free at final treatment visit. These criteria applied separately also resulted in a similar clinical grouping and pattern of response. Differential patterns of response between responders and nonresponders occurred across most clinical measures of panic/anxiety. Responders experienced early improvement within the first week of double-blind treatment. This response progressed during treatment and tended to persist during taper and at followup 1 month later. Post-hoc analysis of demographic and clinical features at entrance into the study failed to characterize this stringently defined group of placebo responders.