Somatic hypermutation profiles in stereotyped IGHV4-34 receptors from South American chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28>D/E, P45>S, E55>Q, and S64>I changes (p < 0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.

Feeding Disorders in Children With Tracheostomy Tubes.

BACKGROUND: We aimed to describe feeding dysfunction in a group of children with tracheostomy. METHODS: Single-center, retrospective chart review of all children with a tracheostomy who were evaluated by our interdisciplinary feeding program. Demographic and diagnostic data, nutrition variables, acceptance of food consistencies, as well as 2 validated psychometric instruments for assessment of feeding dysfunction were analyzed. RESULTS: Thirteen tracheostomy-dependent children (5/13; 38% ventilator dependent) were evaluated at a median age of 51 months (interquartile range [IQR], 26-69). The majority of children (8/13; 62%) underwent evaluation after decannulation. Four children (30%) had a history of a cuffed tracheostomy tube. Eleven children (85%) used a speaking valve prior to decannulation, only 2 of whom started before initial discharge with a tracheostomy. Children with a tracheostomy had low-median weight- and height-for-age z-scores (-1.27 and -1.73, respectively), with normal-median body mass index (BMI)-for-age z-score (0.175). Children received 75% of feedings via tube feeding (IQR, 13%-97%). Compared with other children with feeding disorders, children with tracheostomy had delays in initial acceptance of most food textures and general diet, and the Mealtime Behavior Questionnaire showed significantly worse overall scores (P = .01), and the About Your Child's Eating survey showed significantly higher parental perception of resistance to eating (P = .0001). CONCLUSION: Requirement of enteral nutrition, poor oral-feeding skills, chronic malnutrition, and worse mealtime behaviors are associated with tracheostomy. A history of ventilator dependence, cuffed tracheostomy, and inpatient speaking valve-use were infrequently associated with interdisciplinary feeding-program evaluation.

Intracellular distribution of p300 and its differential recruitment to aggresomes in breast cancer.

It has been recently suggested that p300 cytoplasmic redistribution and degradation are important for controlling the availability and activity of the protein as a transcriptional coactivator. As a step towards determining the functional relevance of p300 intracellular redistribution in mammary cancer, we aimed at studying p300 localization in two different animal models of mammary carcinoma as well as in human primary breast carcinoma samples. Analysis of p300 protein levels showed stronger expression in tumor epithelia than in normal mammary gland. Cytoplasmic localization of p300 was observed in malignant cells. Furthermore, cytoplasmic p300 was found in tumor epithelia whereas nuclear localization was observed in normal mammary glands in both animal models and in non-malignant adjacent areas of human breast cancer specimens. Interestingly, proteasomal inhibition induced p300 redistribution to perinuclear inclusion bodies in tumor but not in normal mammary gland-derived cells. These inclusions were confirmed to be aggresomes by doing immunofluorescence for ubiquitin, vimentin and 20S proteasomal subunit. Taken together, these findings show that both the localization of p300 and the recruitment to aggresomes differ between mammary tumors and normal mammary glands, and suggest that the formation of these inclusions could be a potential target for therapeutic intervention.

Readiness for discharge in parents of hospitalized children.

Parental preparation for a child's discharge from the hospital sets the stage for successful transitioning to care and recovery at home. In this study of 135 parents of hospitalized children, the quality of discharge teaching, particularly the nurses' skills in "delivery" of parent teaching, was associated with increased parental readiness for discharge, which was associated with less coping difficulty during the first 3 weeks postdischarge. Parental coping difficulty was predictive of greater utilization of posthospitalization health services. These results validate the role of the skilled nurse as a teacher in promoting positive outcomes at discharge and beyond the hospitalization.

The study circle as a tool in multiple sclerosis patient education in Sweden.

OBJECTIVE: Patient education plays an important role in the management of chronic diseases that can cause disability and predictable psychosocial problems. Quality of life assessment in multiple sclerosis (MS) has confirmed that psychosocial complications related to working life, marriage/partnership, and the family often occur. Furthermore, symptoms such as fatigue, pain, and sexual dysfunction have a great impact. We wanted to develop and implement study circles to promote the patients' abilities to meet such common problems and to provide a network where they can be autonomous and develop appropriate strategies in self-care and existential problems. METHODS: Together with the MS patient organization and a study association, we have arranged study circles for patients with MS, thus providing structured information according to a pedagogic model. The patients are encouraged to work together in groups to learn about the disease and its key symptoms, to develop strategies to master these symptoms in everyday life, and to make necessary changes, ie, self-care management. The programme also contains handicap policies. RESULTS: Fifteen study circles with a total of 105 patients started during the first year. Fifteen circle leaders were approved. A focus interview showed that the patients are highly satisfied but also revealed some problems in interactions with health care professionals. The study circles were included in a wider project from a newly started multidisciplinary centre for health education for a variety of chronic diseases causing disability, which aims at becoming a regional interface between the health care system, patient organizations, and educational services. CONCLUSION: The study circles have an important role to play in the management of MS. Good organization is required to make such a project work since health care services do not normally work so closely with patient organizations and educational services. PRACTICE IMPLICATIONS: Study circles that are permanently established and function well are of great help for the patients and the work at the MS clinic is substantially facilitated. Health care professionals also gain from the arrangement by learning more about the self-perceived impact of the disease.