Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

The association between social isolation and musculoskeletal health in older community-dwelling adults: findings from the Hertfordshire Cohort Study

Quality of Life Research - Social isolation has been associated with both physical and psychological adverse outcomes and is prevalent in older adults. We investigated the impact of social...     

The impact of frequency,pattern, intensity,and type of alcohol consumption,and its combined effect with smoking on inflammation,lipid profile,and the risk of myocardial infarction

Journal of Public Health - To determine the risk of myocardial infarction (MI) associated with pattern, frequency, and intensity of alcohol consumption, type of alcoholic beverage, and the combined...     

An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumours.

A series of 41 fresh and 36 routinely processed malignant melanomas were immunostained with a panel of 12 monoclonal antibodies reactive against a range of epithelial, lymphoid, and melanoma associated antigens. The aim of the study was to determine whether this panel of antibodies would be useful in diagnostically difficult cases for differentiating melanomas from other tumours, particularly carcinomas and lymphomas. The results confirmed that most unequivocal malignant melanomas can be identified by positivity for S100 protein and for the antigen recognised by antibody NK1/C3, and by negativity for epithelial and lymphoid antigens. The incidence of melanomas expressing cytokeratin antigens was higher, however, particularly in cryostat sections than has previously been reported. It is therefore suggested that a panel of antibodies with more than one marker in each category should be used for identifying melanomas in clinical practice.     

Pharmacokinetics,cerebrospinal fluid penetration,and metabolism of piroxantrone in the Rhesus monkey

Summary Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activityin vitro and less cardiac toxicity than the anthracyclines. The metabolic pathways and central nervous system penetration of piroxantrone have not been determined. In this study we examined the pharmacokinetic behavior of piroxantrone in plasma and cerebrospinal fluid in a non-human primate model. In addition, a urinary metabolite of piroxantrone was isolated and its cytotoxicity evaluatedin vitro. The disappearance of piroxantrone from plasma after an intravenous dose of 150 mg/m² given over 60 minutes was biexponential with mean t_1/2 alpha of 1.0 minutes and a mean t_1/2 beta of 180 minutes. The mean area under the curve was 220 M·min and the clearance was 1420 ml/min/m². Piroxantrone was not detectable in the cerebrospinal fluid.Piroxantrone and three other compounds not present in pre-treatment samples were detected in urine. The major urinary metabolite was isolated. Its cytotoxicity against MOLT-4 cellsin vitro was at least one log less than that of piroxantrone. In addition, one of the other compounds detected in urine was determined to be a glucuronide conjugation product of the major metabolite.The results of this study may be useful in the interpretation of the activity and toxicity of piroxantrone in clinical trials.     

Schedule dependent potentiation of antitumor drug effects by α-difluoromethylornithine in human gastric carcinoma cells in vitro

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with -difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.     

Surface-Attached Polymer Networks Made from Cationic Poly(diitaconates): Synthesis,Surface Characterization,and Bioactivity

Facially amphiphilic polymers carrying cationic and hydrophobic groups on the same repeat unit have shown promising antimicrobial activity and biocompatibility, yet they are prone to suffer from protein adhesion which may induce biofilm formation. To overcome this problem, poly(diitaconate)-based copolymers with cationic/hydrophobic and protein-repellent/charge-neutral repeat units are synthesized. The bioactivity profile of surface-attached polymer networks made from these copolymers depends on the ratio of the cationic and charge-neutral repeat units. In all cases, the protein adhesion is substantially reduced compared to purely cationic polymers. At a 50:50 ratio, the polymer coatings are partially protein-repellent and antimicrobial, yet slightly cell toxic. At an intermediate composition of 30:70, they are still antimicrobial and the cell compatibility is substantially improved. The long-term stability of these materials still has to be determined to judge their suitability for medical applications.     

Functional development of the meso- and metanephros

 This review highlights the important roles the mesonephros may play in development. In the ovine fetus it is an excretory and endocrine organ and may contribute to the formation of normal gonads and adrenals. The metanephros of the ovine fetus has the important function of providing large quantities of dilute urine for the maintenance of amniotic and allantoic fluid volumes, essential for normal placentation and development. Received: 16 March 1998 / Revised: 7 May 1998 / Accepted: 7 May 1998