Exogenous lung surfactant: effect on radiographic appearance in premature infants

At birth, premature infants of 25-29 weeks gestation, at high risk for development of neonatal respiratory distress syndrome (RDS), were given a single dose (90 mg) of calf lung surfactant extract (CLSE) by intratracheal instillation. The frequency and severity of RDS were assessed with use of a simple radiographic scoring system in which pulmonary parenchymal densities and the prominence of the air-bronchogram effect were used as indicators of widespread atelectasis. Radiographs were obtained in surfactant-treated and control infants within the first 90 minutes of life as part of an initial evaluation of their pulmonary status. Subsequent examinations were performed at less than 24 hours and less than 48 hours of age. Radiographic assessment of lung disease compared consistently with coordinated data on oxygen and mean airway pressure requirements of the infants. Both indicated a significantly decreased frequency and severity of RDS in the infants treated with surfactant. The results provide supporting evidence of the effectiveness of exogenous lung surfactant replacement in mitigating RDS in very premature infants.     

Alcohol Use among Injured Patients Aged 12 to 18 Years

Objective : To examine the scope of alcohol use among a population of injured adolescents.
Methods : A convenience sample of injured patients aged 12–18 years seen at a pediatric ED was tested for the presence of alcohol. Injured patients seen within 6 hours of their injuries were asked to submit urine samples for testing using reagent strips. Data were collected from the patient, out-of-hospital emergency care personnel, and parents regarding the circumstances of the injury.
Results : Of the 243 injured patients who were tested during an 8-month period, 231 were included in the final analysis. Ninety patients (39%) were alcohol-positive. The mean age of the alcohol-positive group was 16.0 ± 1.64 years, compared with 15.3 ± 1.8 years for the alcohol-negative group (p < 0.003). There was no significant difference between the 2 groups based on race, gender, or injury characteristics. A positive urine alcohol test was found for 18 (33%) of the motor vehicle crash victims, 9 (38%) of the motor vehicle drivers, 10 (37%) of the patients who attempted suicide, and 49 (44%) of the assault victims.
Conclusions : A substantial percentage of injured adolescent patients were alcohol-positive. The authors recommend the use of alcohol screening when treating injured adolescents.     

Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes

Indoleamine 2,3-dioxygenase (IDO), a flavin-dependent enzyme that catalyzes the conversion of tryptophan to kynurenine, is induced in peripheral blood mononuclear cells by interferon-gamma (IFN gamma). Interleukin-4 (IL-4) is a cytokine that modulates the functional properties of monocytes/macrophages, and we investigated the effects of IL-4 on IDO. We showed that IL-4 inhibited the induction of IDO mRNA and IDO activity by IFN gamma in human monocytes. The inhibitory effect was evident with as little as 2 U/mL of IL-4. These results provide the first evidence that a cytokine can provide a negative signal for IDO expression and that IL-4 can influence the catabolism of tryptophan.     

Protein-tyrosine kinase p72syk in Fc gamma RI receptor signaling

In this report we show that gamma-interferon (IFN) induces the expression of the nonreceptor protein tyrosine kinase, p72syk, and that cross-linking the Fc gamma RI receptor in IFN-differentiated U937 cells (U937IF cells) results in the activation of syk kinase. We show that syk is tyrosine phosphorylated (12-fold increase) after Fc gamma RI cross-linking. In vitro kinase assays demonstrate that the specific kinase activity of syk increased eightfold after Fc gamma RI cross- linking. The activation of signal transduction through the Fc gamma RI receptor, as measured by the respiratory burst, is associated with the tyrosine phosphorylation and catalytic activation of the syk kinase. We show that syk coprecipitates with the gamma subunit of the Fc gamma RI, Fc gamma RI gamma. The data suggest that p72syk is involved in signal transduction through the Fc gamma RI receptor, involving the Fc gamma RI gamma subunit.     

Serological status: a predictor of response to intensive therapy in rheumatoid arthritis

BackgroundRheumatoid arthritis is the most common chronic inflammatory disease in the UK. Serological status such as rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity predict poor outcomes. Early intensive treatment regimens targeting remission reduce disease activity, structural damage, and long-term disability. However, we do not know whether all patients with active disease should have such intensive treatment regimens. Can serological status be used to predict the need for intensive therapy?MethodsWe analysed samples from a published randomised controlled trial which compared four treatment regimens in patients with early active rheumatoid arthritis (disease duration <2 years): methotrexate monotherapy, double therapy (methotrexate plus either ciclosporin or prednisolone), and triple therapy (methotrexate plus ciclosporin plus prednisolone). The trial randomised 467 patients (68% female, median age 54 years [IQR 46–63]). Disease activity was assessed with the disease activity score of 28 joints (DAS28). Remission was defined as DAS28 less than 2·6 at 24 months. RF isotypes (IgM and IgA) and ACPA levels were measured with commercial ELISA kits. Statistical analysis used Pearson's chi-squared test.Findings402 (86%) patients were positive for IgM RF, 346 (74%) for IgA RF, and 346 (74%) for ACPA. 98 (21%) patients achieved remission at 24 months. In RF IgM negative cases (n=65) the proportion of patients achieving remission at 24 months was similar in all treatment groups (25%, 22%, and 30% for monotherapy, double therapy, and triple therapy, respectively). In RF IgM positive cases, significantly fewer patients achieved remission with monotherapy (13/65, 17%) and double therapy (24/157, 15%) than with triple therapy (27/80, 34%) (p=0·001). There were similar, consistent findings with IgA RF and ACPA, with significantly more seropositive patients achieving remission with triple therapy than with monotherapy.InterpretationContemporary treatment of rheumatoid arthritis emphasises the use of intensive therapy to achieve remission. However, we have shown that not all patients require such an aggressive approach to therapy. Given the heterogeneity of the diease, treatment should be personalised to the individual, which would minimise costs of treatment as well as potentially toxic side-effects. Our study shows that only seropositive patients with rheumatoid arthritis should be given more intensive therapies.FundingNational Institute for Health Research.     

Tissue Harmonic Imaging Improves Organ Visualization in Trauma Ultrasound When Compared with Standard Ultrasound Mode

The focused abdominal sonography for trauma (FAST) examination is complicated by brightly lit trauma bays, limited time, and body habitus. Recently, new ultrasound (US) technology has become available that improves organ visualization in abdominal scans. OBJECTIVE: The hypothesis was that a new US mode, tissue harmonic (TH) imaging, improves visualization of critical organ relationships in the FAST examination by making use of previously unused frequencies. The authors performed a blind, prospective observational study to compare the images obtained in typical FAST views with those obtained in standard US and TH modes. METHODS: Blunt trauma patients presenting to a level I trauma center between April and September 2000 were enrolled on a convenience basis. Typical FAST views were obtained in standard and TH modes. The emergency ultrasonographer (EU) switched between modes for each view, optimizing the gain each time. Multiple digital still images were made with all indications of the mode used disguised. For each view on a patient, the best image in each mode was selected in a blinded fashion. Three experienced EUs, blinded to the mode used, rated each image pair for resolution, detail, and total image quality as previously defined on a ten-point Likert scale, 10 being the best for each category. Wilcoxon signed-ranks test, 95% confidence intervals (95% CIs), and interobserver correlation were calculated. RESULTS: A total of 76 image groups (39 of Morison's pouch, 20 splenorenal, and 17 bladder) from 52 patients were rated. Tissue harmonics produced improved resolution, detail, and quality when compared with the standard US mode, with median scores of 6.7 vs. 6.0, 6.7 vs. 6.0, and 6.3 vs. 6.0, respectively. The differences of 0.7 (95% CI = 0.4 to 0.93), 0.7 (95% CI = 0.4 to 0.93), and 0.33 (95% CI = 0.17 to 0.67) were statistically significant, with p = 0.0001, 0.0001, and 0.0003, respectively. There was good interobserver agreement (kappa = 0.74; 95% CI = 0.68 to 0.79). CONCLUSIONS: Tissue harmonics produced FAST images higher in detail, resolution, and total image quality than standard-mode US images.     

Outcomes of a community-based dissemination of the health enhancement program

OBJECTIVES: We previously found in an efficacy trial that a health promotion program prevented functional decline and reduced hospitalizations in community-dwelling older people with chronic conditions. We sought to evaluate the effectiveness of the program in its dissemination phase. DESIGN: Outcome evaluation using a within-group, pretest-posttest design. SETTING: Fourteen senior centers located throughout western Washington. PARTICIPANTS: Three hundred four community-dwelling men and women aged 65 and older. INTERVENTION: A disability-prevention, chronic disease-self-management program. MEASUREMENTS: Participant characteristics, risk factors for disability, change in health and functional status, and healthcare use over 1 year of enrollment; participant satisfaction. RESULTS: Participants were 71% female, had a mean age of 76, and reported three chronic health conditions on average. The percentage of participants found to be depressed decreased (28% at time of enrollment vs 17% at 1-year follow-up, P =.005). The percentage of physically inactive participants decreased (56% vs 38%, P =.001). Physical activity level and exercise readiness improved (Physician-based Assessment and Counseling for Exercise mean score 4.3 vs 5.1, P =.001). At follow-up, 83% rated their health the same as or better than a year ago, compared with 73% at time of enrollment. The proportion with impaired functional status, as measured by bed days and restricted activity days, stayed the same. The proportion hospitalized remained stable (23% at enrollment and follow-up, P = 1.0). CONCLUSIONS: Under real world conditions, the Health Enhancement Program reaches older people at risk of functional decline. Those enrolled for 1 year experience a reduction in disability risk factors, improvement in health status, no decrements in functional status, and no increase in self-reported healthcare use.     

Prevention of increases in blood pressure and left ventricular mass and remodeling of resistance arteries in young New Zealand genetically hypertensive rats: the effects of chronic treatment with valsartan, enalapril and felodipine

The relative efficacy of three antihypertensive drugs in the prevention of further elevation of blood pressure (BP) and cardiovascular structural remodeling in 4-week-old genetically hypertensive (GH) rats was studied by means of two complementary methods, stereology and myography. Four to 10-week-old GH rats were treated with valsartan (10 mg/kg/day), enalapril (10 mg/kg/day) or felodipine (30 mg/kg/day). Untreated GH and normotensive control rats of Wistar origin served as controls. Tail-cuff systolic SBP was measured weekly and left ventricular (LV) mass determined at the end of the experiment. Mesenteric resistance arteries (MRA) were either fixed by perfusion, embedded in Technovit and sections stained for stereological analysis, or mounted on a wire myograph for structural and functional measurements. BP and LV mass were significantly reduced by all drugs; decreases in BP and LV mass were smaller after felodipine treatment. Valsartan and enalapril caused a decrease in BP to normotensive control values. Felodipine kept BP at the 4-week level and prevented further rise with age. Valsartan caused hypotrophic outward remodeling of MRA, enalapril eutrophic outward remodeling and felodipine hypotrophic remodeling. Myograph measurements showed remodeling of the same order. While all drugs lowered the media/lumen ratio in GH to normal, the outward remodeling after valsartan and enalapril indicates that valsartan and enalapril might be more effective in reversing the inward remodeling of resistance arteries found in essential hypertension.     

Chest physiotherapy in infants with cystic fibrosis: To tip or not? A five‐year study

There is controversy about the need for postural drainage physiotherapy in asymptomatic infants with cystic fibrosis (CF). We aimed to compare the effectiveness of standard postural drainage chest physiotherapy (SPT) with a modified physiotherapy regimen without head-down tilt (MPT) in young infants with CF. Twenty newly diagnosed infants with CF (mean age, 2.1 months; range, 1-4) were randomized to SPT or MPT. Parents kept a detailed symptom and treatment diary for the following 12 months. Serial chest radiographs, taken at diagnosis, 12 months, 2(1/2) years, and 5 years after diagnosis, were assessed using the Brasfield score. Pulmonary function tests were compared between groups after 5 years. Of the 20 infants, 16 (80%) completed the review at 12 months, and 14 (70%) at 2(1/2) and 5 years. Patients receiving SPT had more days with upper respiratory tract symptoms than those on MPT (70 +/- 32.8 vs. 37 +/- 24.9 days; P = 0.04) and required longer courses of antibiotics (23 +/- 28.5 vs. 14 +/- 11.2 days; P = 0.05). Chest x-ray scores were similar at diagnosis but were worse at 2(1/2) years for those receiving SPT (P = 0.03). Forced vital capacity and forced expired volume in 1 sec (FEV(1)) at 5-6 years was lower for SPT than for MPT (P < 0.05). In conclusion, MPT was associated with fewer respiratory complications than SPT in infants with CF.