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Patients taking adjuvant endocrine therapy (AET) after breast cancer face adherence challenges and symptom-related distress. We conducted a randomized trial to evaluate the feasibility, acceptability, and preliminary efficacy of a telehealth intervention (Symptom-Targeted Randomized Intervention for Distress and Adherence to Adjuvant Endocrine Therapy [STRIDE]) for patients taking AET.From October 2019 to June 2021, 100 patients reporting difficulty with AET were randomly assigned to either STRIDE or a medication monitoring (MedMon) control group. STRIDE included six weekly small-group videoconferencing sessions and two individual calls. We defined feasibility as having50% of eligible patients enroll,70% complete the 12-week assessment, and 70% of STRIDE patients complete ≥4/6 sessions. We monitored adherence with the Medication Event Monitoring System Caps (MEMS Caps). At baseline and 12- and 24-weeks after baseline, patients self-reported adherence (Medication Adherence Report Scale), AET satisfaction (Cancer Therapy Satisfaction Questionnaire), symptom distress (Breast Cancer Prevention Trial-Symptom Checklist), self-management of symptoms (Self-efficacy for Symptom Management-AET), coping (Measure of Current Status), quality of life (QOL; Functional Assessment of Cancer Therapy-Breast), and mood (Hospital Anxiety and Depression Scale). We used linear mixed effects models to assess the effect of STRIDE on longitudinal outcomes.We enrolled 70.9% (100/141) of eligible patients; 92% completed the 12-week assessment, and 86% completed ≥4/6 STRIDE sessions. Compared with MedMon, STRIDE patients reported less symptom distress (B[difference] = -1.91; 95% CI, -3.29 to -0.52; p = .007) and better self-management of AET symptoms, coping, QOL, and mood. We did not observe significant differences in AET satisfaction or adherence.STRIDE is feasible and acceptable, showing promise for improving outcomes in patients taking AET after breast cancer.Patients taking adjuvant endocrine therapy (AET) after breast cancer may face challenges while following their treatment regimen. In this randomized controlled trial of 100 patients taking AET, a brief, small-group virtual intervention (STRIDE) was well-received by patients and led to improvements in how upset patients were due to symptoms, how confident they were in managing symptoms, and how well they could cope with stress. Thus, STRIDE is a promising intervention and should be tested in future multi-site trials.

Hiatus hernia (HH) contributes to development of gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma. This study was aimed to investigate the influence of HH on reflux patterns and distal esophageal mucosal integrity in non-erosive reflux disease (NERD).We retrospectively analyzed PPI-refractory NERD patients referred to three tertiary referral centers who underwent high-resolution manometry and off-PPI 24-h impedance-pH monitoring (with or without bile spectrophotometry). Patients with HH ≥2 cm (HH group, n = 42) or no HH (non-HH group, n = 40) with similar esophageal acid exposure time (AET 6%-12%) were included.Age, gender, BMI, esophageal motility, AET, and esophageal clearance were similar between the two groups. The HH group had higher numbers of total reflux episodes (p = 0.015) with similar proportion of acid/non-acid reflux compared with the non-HH group. Mean nocturnal baseline impedance (MNBI) in the distal esophagus was significantly lower in the HH group than the non-HH group at both 5 cm (p = 0.002) and 3 cm (p = 0.015) above the lower esophageal sphincter. Multivariable regression analysis showed that HH, less non-acid reflux and lower post-reflux swallow-induced peristaltic wave index (PSPWI) were independently associated with lower MNBI. Among 31 patients tested with bile spectrophotometry, the HH group had significantly longer bile exposure time than the non-HH group (p = 0.011), and bile reflux inversely and significantly correlated with MNBI (rho = -0.75, p lt; 0.001).Hiatus hernia, less non-acid reflux and lower PSPWI were associated with lower MNBI. HH impairs distal esophageal mucosal integrity, the mechanism of which we speculate to be through excessive bile reflux.

Background and Objectives Intravascular haemolytic reactions are reported in red-cell T-activated patients after blood transfusion. The relationship between T antigen antibodies present in normal plasma and these reactions remains unclear. In this study, we assessed the haemolytic activity of T antibodies in vitro in comparison with anti-A/B antibodies. Materials and Methods We established a haemolysis assay based on treating target red-blood-cells (RBCs) with 2-aminoethylisothiouronium bromide (AET). Two hundred and seven blood donor sera were analysed for anti-T, anti-A/B haemolysins and anti-T agglutinins. Results Anti-T haemolysins were found in 4 (1·9%) blood donor sera using a standard haemolysis method and in 174 (84%) samples using AET-treated RBCs. Haemolysis correlated with agglutination titres (P

A report is given of the relative and absolute distribution of lymphocytes carrying three T or B cell specific markers in cord blood; in children and in the blood of healthy adult human subjects. The determinations were performed from stained cytological cell smears under conditions where no subclass specific lymphocyte selection or depletion takes place. In adult blood 78 896 (S. D.) (1.2 0.4 109/1) of lymphocytes expressed the acid α-naphthyl acetate esterase (ANAE) marker. The percentage distribution of the ANAE marker-carrying lymphocytes was stable in different age groups. The absolute values in cord blood and in young children were approximately three times higher than in adults. A somewhat smaller fraction of adult lymphocytes (5314%; 1.0 0.4 109/1) formed rosettes with 2-amino-ethylisothiouronium bromide-hydrobromide (AET) sensitized sheep erythrocytes (AET-SRBC). Although the relative distribution of AET-SRBC rosette-forming lymphocytes was slightly lower in children than in adults, the absolute numbers were approximately two to three times higher. The number of surface Ig-carrying lymphocytes, as detected by rosette formation with Staphylococcus aureus strain Cowan I (StaCw) bacteria in adolescent and adult blood was 19 11 % (0.4 0.2 109/1). The relative number of surface Ig-carrying lymphocytes varied very little in the different age groups. The absolute numbers in cord blood and in small children were approximately twice as high as in adults. The distribution of lymphocytes carrying the fourth marker, surface receptor for IgG, was investigated by antibody-coated human erythrocytes (EA). In adults, the number of lymphocytes forming rosettes with EA was 30 10 % (0.7 0.3 109/1). Although the relative values were somewhat lower in children, the absolute values were approximately twice as high as in adults.

Studies were designed to determine whether AET and cysteamine would alter DNA synthesis in mammalian hemic cells. in vivo studies were performed on young male Swiss mice injected with tritiated thymidine, and in vitro studies were made with bone marrow from either hybrid or Swiss mice. In the in vitro studies a one-hour exposure to tritiated thymidine was allowed. It was shown that AET administered to mice, at times and concentrations compatible with its use as a radioprotective agent both in vitro and in vivo leads to a marked inhibition of DNA synthesis. Cysteamine also inhibited bone-marrow DNA synthesis in vitro. (H.M.G.)

Nitric oxide (NO) produced by macrophages is thought to contribute to various pathological conditions. Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of NO production. However, the relationship between NO and endogenous OPN in activated macrophages has not yet been elucidated. We therefore examined expression of endogenous iNOS and OPN in a murine macrophage cell line, RAW 264.7 cells, by treating the cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Treatment of cells with LPS and IFN-gamma resulted in an increase of iNOS mRNA to maximum at 12 h after stimulation. In contrast, OPN mRNA was induced more slowly than iNOS mRNA. Induction of both iNOS and OPN mRNA in RAW 264.7 cells was markedly suppressed by addition of the specific iNOS inhibitor S-2-aminoethyl isothiourea dihydrobromide. The NOS inhibitor NG-methyl-L-arginine also suppressed induction of OPN mRNA but hardly affected iNOS mRNA expression. The NO-releasing agent spermine-NONOate but not peroxynitrite enhanced induction of OPN mRNA. These results suggest that NO directly up-regulates the endogenous OPN in macrophages stimulated with LPS and IFN-gamma. This up-regulation of endogenous OPN may represent a negative feedback system acting to reduce iNOS expression.

Specificity of IgG autoantibodies that react with random red cell samples but not with cells treated with 2-aminoethylisothiouronium bromide (AET)-previously was related to the Kell blood group system. We now describe an IgG autoantibody, from a patient who died with autoimmune hemolytic anemia, that reacted with random red cell samples, Ko cells, and with cells treated with a dithiothreitol-papain solution, but did not react with AET-treated cells or with Rhnull cells. Serological reactivity of the autoantibody is unlike that of IgG autoantibodies that do not react only with Rhnull cells. It appears that the reactive antigen is not part of the Kell or Rh systems, but is probably modified by the membrane anomaly present in Rhnull red cells.

Summary Serological and structural changes of surface markers involved in immune reactions may occur in human and murine tumour systems. Thus nine out of twenty-one human tumour cell lines and SV40-transformed fibroblasts differed from autologous lymphoblastoid cells or fibroblasts in their reactivity with HLA allonatisera. H-2 antigens isolated from the murine tumour cells 6C3HED and TP 1422, undergo structural changes. An alien HLA-B7 was detected in sera from two melanoma patients. The serologic activity on H-2 antigens was significantly increased in the serum and ascites fluid of tumour bearing mice. Additionally, human SV40-transformed fibroblatsts acquire receptors for monkey red blood cells and the murine lymphosarcoma cells 6C3HED express receptors for sheep red blood cells.

The third Pt(a+) family is described and it has been shown that the red cell antigen is denatured when treated with proteolytic enzymes, but unaffected by neuraminidase and 2-aminoethylisothiouronium bromide treatment.

Summary. The total complement (C′) titre, the concentration of the third component of C (C′3) and the haemolytic activity against AET-treated cells (PNH-like cells) of normal and cirrhotic sera have been investigated. Serum haemolytic activity has been judged by the amount of haemolysis obtained in two in-vitro tests, the acidified-serum test and the sugar-haemolysis test. A significant correlation has been found between total C’ titre and C′3 concentration of cirrhotic sera and the serum haemolytic activity against AET cells in the sugar-haemolysis test.

Summary. The variability with time of the serum haemolytic activity of normal subjects in the acidified-serum and sucrose-haemolysis tests towards the red cells of paroxysmal nocturnal haemoglobinuria (PNH) and PNH-like cells (i.e. normal red cells treated in vitro with the sulfhydryl compound AET) was investigated. A wide variability was observed in samples of serum obtained from individual donors at intervals of months, days, and even hours, without evidence of a circadian rhythm. In spite of this variability each donor of serum, considered in respect to other donors, maintained unchanged with time his rank of serum haemolytic activity towards both PNH and AET cells in the acidified-serum test, but not in the sucrosehaemolysis test. From the practical point of view it seems convenient for the laboratory diagnosis of PNH to carry out acidified-serum tests with the serum of one selected normal subject (in addition to the patient's own serum) and sucrosehaemolysis tests with a few random normal sera.

Red cells incubated with N-acetylcysteine or D-penicillamine in appropriate concentrations become sensitive to lysis by acidified normal human serum, i.e. become PNH-like cells and give a positive Ham test. At the same time the cells lose some of their acetylcholinesterase activity. Substances active in this way share a common chemical grouping

Summary. In paroxysmal nocturnal haemoglobinuria (PNH) the intensity of haemolysis obtained in the acidified-serum and sucrose-haemolysis tests—the two procedures most commonly used for the laboratory diagnosis of the disease—varies according to the red cells, serum and test used. The influence of these three variables has been investigated on both PNH and PNH-like lysis, that is lysis of PNH cells and of normal red cells treated in vitro with the sulphydryl compound 2-aminoethylisothiouronium bromide (AET). The conclusions, almost identical for PNH and AET lysis experiments, suggest that for the laboratory diagnosis of PNH: (1) it is advisable to use both tests in parallel; (2) sera to be used in the two tests should be selected; (3) for this selection AET cells can be employed when PNH cells are not available.