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Background MAT9001 is an omega‐3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA‐ethyl esters [EE]), EPA+DPA‐FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very–low fat diet. This trial compared pharmacodynamic responses and plasma omega‐3 levels following twice daily dosing, with meals, of EPA+DPA‐FFA and EPA‐EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. Methods and Results This open‐label, randomized, 2‐way crossover trial, with 28‐day treatment periods separated by ≥28‐day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150–499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA‐FFA and EPA‐EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively ( P =not significant). EPA+DPA‐FFA reduced least squares geometric mean high‐sensitivity C‐reactive protein by 5.8%; EPA‐EE increased high‐sensitivity C‐reactive protein by 8.5% ( P =0.034). EPA+DPA‐FFA increased least squares geometric mean plasma EPA, DPA, and total omega‐3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA‐EE of 692%, 140%, and 165% (all P P =0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. Conclusions EPA+DPA‐FFA raised plasma EPA, DPA, and total omega‐3 significantly more than did EPA‐EE. EPA+DPA‐FFA also reduced triglycerides and high‐sensitivity C‐reactive protein without increasing low‐density lipoprotein cholesterol. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04177680.

Probiotic, prebiotic, and synbiotic (a combination of pro- and prebiotic) supplements increasingly are being used to prevent and treat a variety of health conditions. Although colonization is considered a key element in the success of such treatments, few clinical studies have addressed colonizing ability. Studies are even more limited in neonates and infants, who may benefit most from such treatment. The present study was conducted to determine the colonizing ability, tolerance, and impact on the stool flora of 7 days of administration of a synbiotic supplement to a neonatal cohort, in preparation for a larger hospital-based trial.In this randomized, double-masked, controlled trial, healthy inborn newborns35 weeks of gestational age and1800 g birth weight were randomized between 1 and 3 days after birth to receive an oral synbiotic preparation (Lactobacillus plantarum and fructooligosaccharides) or a dextrose saline placebo. Two babies were treated with the synbiotic preparation for every 1 baby treated with the placebo. Duration of therapy was 7 days. Comprehensive stool cultures were done at baseline and on days 3, 7, 14, 21, and 28.Nineteen infants received the active study supplement and 12 infants received the placebo for 7 days. L plantarum was cultured from the stools of 84% of the treated infants after 3 days of treatment, and from 95% of infants on day 28 after birth. Of the infants, 100%, 94%, 88%, 56%, and 32% remained colonized at months 2, 3, 4, 5, and 6, respectively. In both groups, the total mean number of species and the mean log colony counts increased over time. The number of bacterial species was significantly higher on days 21 and 28 in the synbiotic preparation group compared with placebo (P = 0.002 and 0.03, respectively). There was a linear increase in the mean log gram-negative colony counts in the placebo group during the 4-week period that was significantly higher than that in the Lactobacillus group on days 14, 21, and 28 (P0.001 for each). In contrast, the supplement group had significantly higher gram-positive colony counts on days 14 (P = 0.002) and 28 (P = 0.04). Only 1 infant in the placebo group was colonized with L fermentum during the first 28 days of life. No difference was found in the percent increase in weight between baseline and day 7, but on day 28 and months 2, 3, and 6, the percent increase from baseline was higher in the probiotic-treated group (P/= 0.05). The supplement was tolerated well.The synbiotic preparation colonized quickly after 3 days of administration and the infants stayed colonized for several months after therapy was stopped. There was an increase in bacterial diversity and gram-positive organisms and a reduction of gram-negative bacterial load in the treatment group. Because a combination preparation was used, it is difficult to specifically attribute the colonization to either the probiotic or prebiotic component in this study. Larger efficacy trials are warranted to examine the mechanism of action and precise effects of these supplements.

Objectives Identification of risk factors is important for preventing radiocontrast-induced nephropathy (RCIN). Contrast dose and renal function have been shown in most but not all studies to be risk factors for RCIN. We are investigating the ratio of contrast dose to creatinine clearance (D/CrCL) as a risk indicator. Theory shows that the D/CrCL ratio equals the area under the concentration-time curve (AUC), an accepted measure of systemic exposure. This study investigated the correlation between calculated D/CrCL and experimentally measured AUC for the contrast agent iodixanol. Materials and methods Experimental data on AUC from a phase 1 study of iodixanol were plotted against the D/CrCL ratio and the degree of correlation was determined. Results Experimentally determined AUC data correlate highly with the D/CrCL ratio. Conclusions The D/CrCL ratio is a rapid and accurate way to estimate AUC for an iodinated x-ray contrast agent without the need for multiple blood samples.

University of Munich, and To extend previous studies on the anti-inflammatory role of interleukin (IL)-10 in vivo, mice pretreated with IL-10 were subjected to ionizing radiation (IR), lipopolysaccharide (LPS), or both and assessed for the expression of the intercellular adhesion molecule 1 (ICAM-1) in immunohistochemical analyses. IL-10 was able to almost fully protect LPS+IR-treated animals against ICAM-1 up-regulation. Because LPS and IR also increased adhesion of peripheral blood mononuclear cells, transendothelial migration assays were performed to investigate the functional significance of these findings. IR was found to induce transendothelial migration, and this effect could be enhanced by cotreatment with LPS, in the same fashion as peripheral blood mononuclear cell adhesion. Also in this system, IL-10 proved to act as a potent LPS antagonist. Finally, in vivo immunohistochemical analyses revealed an infiltration of CD3 + T lymphocytes into organs that were the target of transplant-related complications after LPS+IR treatment. This infiltration could also be completely reversed by IL-10 pretreatment.

Although a variety of studies exists, the silicone controversy is still going on. In the present study we investigated the expression of the activation markers CD44-v6, intracellular adhesion molecule 1 (ICAM-1), and HLA class II molecules on breast epithelia adjacent to a silicone gel-filled breast implants (SGBI). Using an indirect immunoperoxidase procedure 12 tissue samples from implant recipients were investigated and 6 tissue samples from patients with slight breast hyperplasia were used as controls. Expression of CD44-v6 was found on ductal epithelia in all specimens from implant recipients, HLA-DR was expressed in all specimens, HLA-DQ in 3 of 10, and ICAM-1 in 8 of 12. In contrast, neither CD44-v6 nor HLA-DQ nor ICAM-1 were expressed on ductal epithelia from patients with slight breast hyperplasia, and HLA-DR was only weakly expressed in 2 of 6 patients. These data show that CD44-v6 can be expressed by benign cells under certain conditions, which may indicate an abnormal state of activation in breast tissue adjacent to an SGBI.

The cell surface glycoprotein MUC18 was originally identified as a progression associated antigen in melanoma. MUC18 is expressed most strongly on metastatic lesions and advanced primary tumours and is only rarely detected in benign lesions. cDNA cloning revealed MUC18 to be a novel member of the immunoglobulin superfamily with sequence similarity to a number of cell adhesion molecules. Cloning of both the human and mouse MUC18 genes indicate that their predicted protein structures are very similar with an overall amino acid identity of 75%. Like its human counterpart, murine MUC18 is also expressed by transformed melanocytes. Analysis of the promoter region of the human gene has provided evidence for regulatory elements found in smooth muscle specific genes and in both human and mouse: this is the normal site of MUC18 expression. The presence of putative binding sites for the transcriptional factors AP-1, AP-2 and CREB, suggest that MUC18 gene expression can also be modulated by external factors.

Intercellular adhesion molecule (ICAM)-1 and mucin isotype MUC18 were originally identified as melanoma progression antigens by monoclonal antibodies (MAb) generated in a search for molecules expressed by melanomas but not detectable on benign naevi. As MAb detect single epitopes whose accessibility may be modulated, a new panel of antibodies directed against distinct epitopes and reacting with denatured nonglycosylated antigen as well as native antigen were used to examine expression of these molecules on melanocytic lesions. The antibodies were analysed in a binding inhibition assay and divided into groups defining independent epitopes. Three anti-ICAM-1 and four anti-MUC18 antibodies representing these groups were then tested on frozen sections of 10 benign naevi and 10 melanoma lymph-node metastases. The anti-ICAM-1 antibodies demonstrated concordant reactivities on both the malignant and benign lesions and reacted with all samples suggesting that antibodies that detect differences in ICAM-1 expression between these two lesions detect altered epitopes. Three of the four antibodies directed to MUC18 showed concordant reactivities and indicated that this molecule was expressed in nine melanomas and three naevi. However, one antibody (MUC18BA.3) reacted strongly with all lesions indicating either crossreactivity with another melanocyte molecule or the expression of a different form of MUC18 on naevi.

The traditional approaches to monitoring reliability and validity are time consuming and costly and frequently lead to the abandonment of reasonable classification instruments. With the advent of micro computers and relational database software, nursing executives are now able to track reliability and validity on an ongoing basis. Because patient classification data are retained, they can be used to provide more accurate work load predictions and descriptions. Further, the ability to identify the source of problems with unit-specific instruments or nurse classifiers leads to the required corrective mechanism. Increased confidence in the reliability and validity of the work load data provides the staff nurse with direct evidence of the accuracy of the patient classification instrument and the nursing executive with a significantly stronger tool in budget planning and tracking, contract negotiations and financial risk reduction.

The author describes the process used to develop a patient classification system in a large multi-specialty ambulatory care facility. The process involved identifying critical indicators for each specialty area, validating the instruments, and calculating the workload. The approach to sampling and the problems encountered for relatively short visits are discussed.

Clinical features, findings of diagnostic studies, results of therapy, and prognostic factors were analyzed in 45 patients with brain abscesses. The number of patients diagnosed yearly has increased since CT scanning became available, but despite the enhanced sensitivity, the time from either onset of symptoms or hospital admission until initiation of therapy was not decreased and there was no dramatic effect upon morbidity or mortality in this series. Infections of paranasal sinuses, ears, lungs, and odontogenic foci were predisposing factors in approximately 70% of cases. Single abscesses, present in 75% of patients, were distributed equally in both hemispheres, with more than half in the frontal and parietal lobes. Common signs and symptoms included headache, fever, chills, seizures, nausea, vomiting, altered sensorium, nuchal rigidity, and localizing neurologic signs. Blood cultures were positive in 11%. Lumbar puncture rarely provided data from which a diagnosis could be established; CSF cultures were positive in only 7% of patients, and there was a 15% temporally associated incidence of brain herniation and death. Diagnostic information was most readily obtained using imaging techniques such as CT and 99mTc scanning, and arteriography was invasive and of no added value. CT scans are however, often initially negative in patients presenting with clinical signs of meningitis presumably following rupture of an abscess into the subarachnoid space, and the average time for changes to appear on CT scan is 9 days. It is, therefore, recommended that when the clinical assessment suggests the possibility of brain abscess the patient be treated empirically with antibiotics and that lumbar puncture be performed only after thoughtful assessment of the risk-to-benefit ratio for each patient. Causative organisms were isolated from more than 80% of abscesses despite prior antibiotic treatment; more than half grew a single pathogen, most commonly streptococci. Anaerobic and microaerophilic bacteria accounted for 62% of all isolates, and were the only organisms in 33% of patients. Computerized tomographic scans in 30 patients showed "ring-enhancing" lesions, nodular enhancement, or areas of low attenuation. Complete resolution of abscesses on CT scans rarely occurred during hospitalization and took as long as 5 months. Decrease in the size of abscesses on CT scan correlated well with clinical improvement and was seen within a week when abscesses were excised, but was often not obvious for 6 to 8 weeks if antibiotics were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)

A great deal of time and energy goes into deciding what software computer system to purchase for the nursing department. Too often following purchase, we think our work is over, when in reality, the most critical phase is starting--installing the system. This article discusses critical responsibilities of both nurse administrators and installers during implementation of the system.