Magnetic silica extraction for low-viremia human immunodeficiency virus type 1 genotyping

Nucleic acid extraction and human immunodeficiency virus type 1 (HIV-1) genotyping using the NucliSens miniMAG platform and the TruGene HIV-1 genotyping kit gave HIV-1 sequence data from HIV-1-negative plasma spiked with 100 copies/ml reference HIV-1 RNA and from low-viremia clinical samples (<500 copies/ml) without the need for ultracentrifugation or nested second-round PCR.     

Lower limb immobilization is associated with increased corticospinal excitability

Temporary immobilization of the leg serves as a useful model for the brain’s adaptive responses to casting, long-term confinement to bed rest and possibly to trauma. As part of a larger program using TMS to investigate changes associated with bed rest, we sought to determine whether casting of the leg causes brain excitability changes measurable with TMS, and the time course of resolution of these changes. In this study, eight adults wore a full leg cast for 10 days. TMS measures of motor cortex excitability were gathered before the cast was placed, and then immediately after cast removal, and 24 and 48 h later. A control group did not wear a cast and underwent the same TMS sessions. Significant excitability changes occurred and peaked at 24 h post cast removal in the TMS experimental group but not the non-casted group.     

Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder--a preliminary tolerability and efficacy study

BACKGROUND: The primary treatment for attention-deficit/hyperactivity disorder (ADHD) has been psychostimulants. Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant. However, the outcomes of such switches have not been systematically studied. OBJECTIVE: The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylphenidate or amphetamine to atomoxetine among children and adolescents with ADHD. METHODS: This pilot study was conducted in patients (aged 6-17 years) with incomplete responses (failure to obtain full reduction/elimination of symptoms) or intolerance of adverse events (AEs) during psychostimulant treatment. Patients continued ongoing psychostimulant treatment during the first week of the study. Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week, followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant. Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks. This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine. Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period. Change in ADHD symptoms, as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), was assessed from baseline to end point. RESULTS: Of the 62 subjects enrolled in the study, 39 (62.9%) were diagnosed as ADHD-combined type. Similar proportions were receiving methylphenidate (51.6%) and amphetamine (48.4%). Slightly more wished to switch due to inadequate response (53.2%) than intolerability (46.8%). Nine subjects discontinued at various times during the course of the study (patient or parent/caregiver decision [4], AE [2], protocol violation [2], and lack of efficacy [1]). Mean (SD) ADHDRS-IV-Parent:Inv total scores (n = 59, last-observation-carried-forward) improved significantly from baseline (visit 2) to an end point (32.1 [10.5] vs 22.6 [14.0]; P < 0.001). Of the 58 subjects answering in the atomoxetine monotherapy phase, 38 (65.5%) reported a preference for atomoxetine treatment over their previous psychostimulant. Tolerability results were as follows: 26 (44.1%) of 59 patients reported >or=1 AE, the most common being somnolence (4 [6.8%]), fatigue (3 [5.1%]), decreased appetite (3 [5.1%]), cough (3 [5.1%]), headache (3 [5.1%]), and contact dermatitis (2 [3.4%]). No clinically severe AEs were reported. Both mean (SD) diastolic (2.4 [7.8] mm Hg; P = 0.031) and systolic (2.4 [7.9] mm Hg; P = 0.029) blood pressures increased significantly from baseline to end point. Electrocardiography revealed a significant increase in mean (SD) heart rate (9.2 [11.6] bpm; P < 0.001) and a corresponding decrease in mean (SD) RR interval (-77.8 [98.2] ms; P < 0.001). Statistically significant, but mild, increases in diastolic pressure and heart rate were observed. CONCLUSION: These children and adolescent patients were successfully switched from methylphenidate or amphetamine to atomoxetine treatment, with resulting improvement in ADHD symptom severity from baseline in this pilot study.     

Identification of Subgroups of Schizophrenia Patients With Changes in Either Immune or Growth Factor and Hormonal Pathways

Schizophrenia is a heterogeneous disorder normally diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. However, these criteria do not necessarily reflect differences in underlying molecular abnormalities of the disorder. Here, we have used multiplexed immunoassay analyses to measure immune molecules, growth factors, and hormones important to schizophrenia in acutely ill antipsychotic-naive patients (n = 180) and matched controls (n = 398). We found that using the resulting molecular profiles, we were capable of separating schizophrenia patients into 2 significantly distinct subgroups with predominant molecular abnormalities in either immune molecules or growth factors and hormones. These molecular profiles were tested using an independent cohort, and this showed the same separation into 2 subgroups. This suggests that distinct abnormalities occur in specific molecular pathways in schizophrenia patients. This may be of relevance for intervention studies that specifically target particular molecular mechanisms and could be a first step to further define the complex schizophrenia syndrome based on molecular profiles.Key words: schizophrenia, subtypes, diagnosis, molecular profiling, immune factors, growth factors     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Circulating interleukin-6 is associated with disease progression,but not cachexia in pancreatic cancer

Background

Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression.

Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis

A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.     

Back to the Future with Phenotypic Screening

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