Nocturnal asthma: underlying mechanisms and treatment.

Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV(1)) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma. Nocturnal symptoms are a common part of the asthma clinical syndrome; up to 75% of asthmatics are awakened by asthma symptoms at least once per week, and approximately 40% experience nocturnal symptoms on a nightly basis. An extensive body of research has demonstrated that nocturnal symptoms such as cough and dyspnea are accompanied by increases in airflow limitation, airway hyperresponsiveness, and airway inflammation.

Do NHLBI lung function criteria apply to children? A cross-sectional evaluation of childhood asthma at National Jewish Medical and Research Center, 1999-2002.

Although National Heart Lung Institute (NHLBI) guidelines categorize asthma severity based on spirometry, few studies have evaluated the utility of these spirometric values in grading asthma severity in children. Asthma is thought to be progressive, but little is known about the loss of lung function in childhood. This study sought to determine the spirometric indices in children from 4-18 years of age.

Increased TGF-beta2 in severe asthma with eosinophilia.

Background: Airway eosinophilia and thickened subepithelial basement membrane have previously been reported to increase with increases in TGF-beta expression. However, little is known regarding the expression of specific TGF-beta isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) in asthma, despite recent evidence suggesting that isoforms may have differing biologic activities.

Objective: This study examined airway tissue expression of the 3 TGF-beta isoforms and several downstream pathway elements in 48 patients with severe asthma with or without persistent eosinophilia, 14 patients with mild asthma, and 21 normal subjects.

Diminished suppression of the P50 auditory evoked potential in bipolar disorder subjects with a history of psychosis.

Objective: People with schizophrenia, schizoaffective disorder, and bipolar illness share clinical symptoms, biological findings, and genetic susceptibility. Diminished suppression of the P50 auditory evoked potential is a phenotype used in studies of genetic susceptibility in schizophrenia. In patients with acute mania, this inhibitory deficit has been correlated with severity of clinical symptoms.

Systemic neutrophil priming by lipid mediators in post-shock mesenteric lymph exists across species.

Background: Post-hemorrhagic shock mesenteric lymph (PHSML) has been linked with neutrophil (PMN) priming, endothelial cell (EC) activation, and acute lung injury (ALI) in rodent models. We have previously identified the lipid fraction of PHSML as containing the causative agent(s). Due to the lesson learned from the rodent gut bacterial translocation experience, we sought to confirm this phenomenon using a large animal model; hypothesizing that lymph collected from the porcine gut following ischemia/reperfusion (I/R) would cause PMN priming.

PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs.

Peroxisome proliferator-activated receptor (PPAR)-gamma modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-gamma activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-gamma activator that has been shown to be protective in I/R in large animals.

Reliability and validity of the proposed American College of Rheumatology neuropsychological battery for systemic lupus erythematosus.

Objective: To examine the reliability and validity of the proposed American College of Rheumatology (ACR) neuropsychological battery for patients with systemic lupus erythematosus (SLE).

Methods: Thirty-one SLE patients with a history of neuropsychiatric symptoms (NPSLE), 22 SLE patients without a history of neuropsychiatric symptoms (non-NPSLE), and 25 healthy controls completed measures of cognition at baseline and after 1 month. The 1-hour proposed ACR-SLE battery was compared with a 4-hour comprehensive battery (CB).

Interleukin-13 augments transforming growth factor-beta1-induced tissue inhibitor of metalloproteinase-1 expression in primary human airway fibroblasts.

Tissue inhibitor of metalloproteinase (TIMP)-1 is a potent inhibitor of activated matrix metalloproteinases (MMPs) such as gelatinases and collagenases. TIMP-1 is induced by transforming growth factor-beta1 (TGF-beta1), but details regarding signaling pathways remain unclear. T-helper-2 cytokines also have profibrotic properties and can interact with TGF-beta.

Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data.

Objective: The issue of thimerosal-containing vaccines as a possible cause of autistic spectrum disorders (ASD) and neurodevelopmental disorders (NDDs) has been a controversial topic since 1999. Although most practitioners are familiar with the controversy, many are not familiar with the type or quality of evidence in published articles that have addressed this issue. To assess the quality of evidence assessing a potential association between thimerosal-containing vaccines and autism and evaluate whether that evidence suggests accepting or rejecting the hypothesis, we systematically reviewed published articles that report original data pertinent to the potential association between thimerosal-containing vaccines and ASD/NDDs.

Effect of 24-hour intravenous tubing set change on the sterility of repackaged fat emulsion in neonates.

Background: Duration of intravenous fat emulsion (IVFE) infusions, precise method of administration (manufactured bottle vs repackaged syringe), and interval for administration set change continue to be debated.

Objective: To determine the contamination rate associated with replacing IVFE administration sets every 24 hours in newborn infants receiving fat emulsion repackaged into unit-of-use syringes.

Methods: This was a prospective, microbiologic study of 90 administration sets used in 19 neonates.

Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia.

Rationale And Objective: Auditory sensory gating, a biological measurement of the ability to suppress the evoked response to the second of two auditory stimuli, is diminished in people with schizophrenia. Deficits in sensory gating are associated with attentional impairment, and may contribute to cognitive symptoms and perceptual disturbances. This inhibitory process, which involves the alpha(7) nicotinic receptor mediated release of gamma-aminobutyric acid (GABA) by hippocampal interneurons, represents a potential new target for therapeutic intervention in schizophrenia.

Receptor editing is the main mechanism of B cell tolerance toward membrane antigens.

Self-reactive B cells specific for ubiquitous membrane-bound autoantigens are eliminated in the bone marrow by two mechanisms of tolerance: receptor editing and clonal deletion. However, the relative contributions of clonal deletion and receptor editing to B cell tolerance in a polyclonal B cell population have not been established. Here we show that tolerance toward a membrane antigen-reactive B cell clone acts by receptor editing with very minimal cell loss.

Financing the treatment of chronic pain: models for risk-sharing among pain medicine physicians, health care payers, and consumers.

Chronic pain patients are among a growing group of medically underserved Americans. Despite increasing public awareness about pain and widespread legislative activity that is focusing on the needs of pain patients, there remain significant roadblocks in bringing the expertise of Pain Medicine specialists to these unfortunate people. This paper explores how the managed care revolution has impacted the practice of Pain Medicine in the United States.

Nutritional support for the burn-injured patient.

The nutritional needs of the bum-injured patient are exaggerated and change constantly with the patient's stage of convalescence. Nurses working closely with other members of the health care team, specifically the nutritional specialist, can positively affect the patient's survival by optimizing the nutritional assessment,delivering enteral feedings that meet established goals,minimizing the negative consequences of hyperglycemia, and minimizing unnecessary energy expenditures by the patient. Adequate nutritional is required for wound healing, immunocompetence, and, ultimately,patient survival.

Consider the child: how early should we treat?

Epidemiologic and natural history studies of asthma have found that, for most people who develop asthma, clinical manifestations of the disease occur in the early childhood years. Both asthma persistence and severity during early childhood predict disease persistence into later childhood and adulthood, at which point asthma remission is uncommon. Current pathogenesis paradigms suggest that early intervention, before serious pathologic changes occur, may lead to optimal outcomes.

Postreduction management of intussusception in a children's hospital emergency department.

Objective: To evaluate the current management of patients with intussusception who have undergone successful reduction by contrast enema in a tertiary care children's hospital. To compare differences in the incidence of recurrence and adverse events between those patients who were hospitalized after enema reduction and those who were observed in the emergency department (ED).

Methods: This was a retrospective cohort study of children 0 to 18 years of age who underwent uncomplicated enema reduction for intussusception.

Pathology of difficult asthma.

Severe asthma is poorly understood clinically, physiologically and pathologically. Although milder forms of asthma are generally easily treated, more severe forms remain refractory to the best current medical care. Both genetic and environmental elements are likely to play an important role in the development of severe disease.

Cervical spine fracture patterns predictive of blunt vertebral artery injury.

Background: Aggressive screening for blunt cerebrovascular injury (BCVI) has uncovered an astonishing incidence of vertebral artery injuries (VAIs) and associated stroke rate. Stroke incidence is reduced with early recognition and prompt anticoagulation. Because of the proximity of the cervical spine and vertebral arteries, we queried whether all patients with cervical spine fractures required arteriography to rule out VAI.

Considering therapeutic options in the real world.

When choosing a drug regimen, physicians can rely on two models: their own clinical experience and results from clinical trials. Both options have problems. Overall, patients with persistent asthma symptoms often have improved outcomes with the use of long-term controller medications on a daily basis to prevent exacerbations of symptoms.

Clinical trial efficacy: what does it really tell you?

The primary goal of most clinical trials is an evaluation of the efficacy of the drug being evaluated. Therefore, it is important to understand if study outcomes are a true reflection of a drug's "real-life" effectiveness. Clinical trials generally evaluate three types of outcomes: subjective, objective, and health-related.

Pharmacoeconomic evaluation of the effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes.

An economic analysis was conducted using clinical outcomes in the MIRACL trial that evaluated high-dose atorvastatin versus placebo for 16 weeks after acute coronary syndrome. The direct cost of atorvastatin was largely offset by the associated decrease in cardiovascular events. The net incremental cost of atorvastatin treatment was 157 dollars/patient with a cost-effectiveness ratio of 4,086 dollars/event avoided.