Requirement for IGF-I in epidermal growth factor-mediated cell cycle progression of mammary epithelial cells

Induction of cyclin proteins is required for progression of cells through the G(1)-S and G(2)-M cell cycle checkpoints and is a primary mechanism by which mitogens regulate cell cycle progression. IGF-I and the epidermal growth factor (EGF)-related ligands are mitogens for mammary epithelial cells in vitro and are essential for growth of the mammary epithelium during development. We report here that IGF-I in combination with EGF or TGFalpha is synergistic in promoting DNA synthesis in mammary epithelial cells in the intact mammary gland cultured in vitro. We further investigated the role of IGF-I and EGF in cyclin expression and cell cycle progression in the mammary gland and demonstrate that IGF-I and EGF induce expression of early G(1) cyclins. However, we show that IGF-I, but not EGF, induces late G(1) and G(2) cyclins and is required for mammary epithelial cells to overcome the G(1)-S checkpoint. These data demonstrate that IGF-I is essential for cell cycle progression in mammary epithelial cells and that it is required for EGF-mediated progression past the G(1)-S checkpoint in these cells.     

Antibacterial agents in pediatrics

From low birth weight infants to adolescents, physiologic and developmental differences underlie the marked differences in pharmacokinetics and pharmacodynamics of antibacterial agents. Certain diseases, such as cystic fibrosis, also can alter these parameters. This article describes the principles of pharmacokinetics and pharmacodynamics that are unique to children and that characterize the clinical application of selected antibacterial agents to infectious diseases in children.     

Surgical treatment of accessory atrioventricular pathways and symptomatic tachycardia in children and young adults

Twenty-seven patients aged 21 years or younger (mean 15) with symptomatic tachycardia underwent operation for ablation of an accessory atrioventricular pathway. Six patients had associated Ebstein's malformation of the tricuspid valve. Supraventricular tachycardia had been present for a mean of 5 years. At electrophysiologic study, 4 patients were found to have 2 accessory pathways. Left ventricular free wall pathways were found In 14 patients, right ventricular free wall pathways in 10 and septal pathways in 6. Successful initial ablation of all the pathways was achieved in 26 of the 27 patients. No patient died perioperatively and none had persistent complete heart block. During a mean follow-up of 11 months, no patient had recurrence of an arrhythmia related to the accessory pathway. Thus, the surgical treatment of children and young adults with accessory atrioventricular pathways and symptomatic supraventricular tachycardia is safe and effective. For these patients, unless the tachycardia can be easily controlled with a minimal number of drugs and adverse effects, surgical ablation should be considered early in the clinical course.     

Evolution of Sezary syndrome in the course of hairy cell leukemia

A patient with a history of "leukemia" for 19 yr and documented hairy cell (HC) leukemia for 10 yr developed mycosis fungoides and the Sezary syndrome. The manifestations of both diseases were diagnostic on clinical and pathologic grounds. Ultrastructural, immunohistochemical, and surface marker techniques proved the HC to have phenotypic characteristics of the T-helper subset of lymphocytes to which the Sezary cells (SC) also belonged. Both types of cells contained tartrate- resistant acid phosphatase. HC did not infiltrate the skin. SC did not contain ribosome lamellar complexes. Because of otherwise overlapping morphology and the apparent replacement of HC by SC, it is likely that the Sezary cells constituted a genetic variant of the original neoplastic clone represented by the hairy cells. Since the biologic and therapeutic implications of such clonal evolution may be important, subtle phenotypic changes should be looked for repeatedly in patients with these diseases.     

Expression of the cutaneous lymphocyte antigen and its counter-receptor E-selectin in the skin and joints of patients with psoriatic arthritis

We have investigated whether the skin-homing T lymphocytes identified by the cutaneous lymphocyte antigen (CLA) are increased in the synovial membrane of patients with psoriatic arthritis. Twenty-six synovial samples (13 psoriatic arthritis, seven rheumatoid arthritis, six osteoarthritis) were obtained from involved knees. Lesional skin biopsies were taken from nine of the patients with psoriatic arthritis and six patients with psoriasis alone. All samples were single- and dual-stained for CLA and CD3 (to identify T lymphocytes) using HECA-452 (anti-CLA) and anti-CD3 monoclonal antibodies. E-selectin expression was also determined. The percentage of dual-stained lymphocytes was significantly greater in psoriatic skin than in synovium (P < 0.001) and similar between psoriatic and rheumatoid synovium. There was no significant difference in the percentages of CLA-positive cells in psoriatic skin in patients with psoriatic arthritis compared with psoriasis alone. The intensity of endothelial E-selectin expression was significantly greater in skin psoriasis than in synovium (P < 2 x 10(- 5)), and rheumatoid synovium had significantly greater expression than psoriatic synovium (P < 0.05). However, there was no significant correlation between E-selectin expression and the percentages of CLA- positive lymphocytes. This study provides further evidence that the CLA antigen is enriched on skin-homing lymphocytes. Conversely, the link between skin and joint inflammation in psoriatic arthritis does not seem to be explained by increased trafficking of CLA T cells to psoriatic synovium.      

Social participation and family carers of people living with dementia in Australia

This paper reports on a study exploring the experiences and meaning of social participation for family carers of people living with dementia. Participants were 33 family carers (17 spouses and 16 adult children) of older adults diagnosed with dementia (any stage or type) who responded to advertisements by the national Alzheimer's association, Alzheimer's Australia. Data were collected through semi‐structured face‐to‐face and/or telephone interviews using an interview guide, which included prompts such as ‘Tell me about what social participation means to you’, and ‘How did this change…’. The methods of grounded theory were drawn upon to guide sampling and analysis of data, which continued until theoretical saturation was achieved and occurred over the period September 2011 to March 2012. Data arising from the interviews were analysed line‐by‐line and coded and categorised using the constant comparative method, with codes clustered into themes and with abstraction from the themes to arrive at the core process. The core category arising from the data was adaptation, which encompassed four main themes: autonomy to choose; the impact of care‐giving; employing strategies; and establishing meaningful connections. Carers went through a process whereby the ways in which they had previously participated socially were compromised, which often prompted an exploration of new ways in which to remain socially engaged.     

Patients' expectations of osteopathic care: a qualitative study

Background

Research has shown that patients'' expectations of health care and health‐care practitioners are complex and may have a significant impact on outcomes of care. Little is known about the expectations of osteopathic patients.

Objectives

To explore osteopathic patients'' expectations of private sector care.

Design

Focus groups and individual interviews with purposively selected patients; this was the qualitative phase of a mixed methods study, the final phase being a patient survey.

Setting and participants

A total of 34 adult patients currently attending for treatment at private osteopathic practices across the United Kingdom.

Intervention

Focus group discussions and individual interviews around expectations before, during and after osteopathic care.

Outcome measures

Thematic analysis of text data to identify topics raised by patients and to group these into broad themes.

Results

Many components of expectation were identified. A preliminary conceptual framework describing the way the therapeutic encounter is approached in osteopathy comprised five themes: individual agency, professional expertise, customer experience, therapeutic process and interpersonal relationship.

Discussion and Conclusion

The components of expectation identified in this phase of the study provided potential question topics for the survey questionnaire in the subsequent phase of the investigation. The model developed in this study may add a new perspective to existing evidence on expectations. Further research is recommended to test the findings both within private practice and the National Health Service.     

Blueberries Improve Endothelial Function,but Not Blood Pressure,in Adults with Metabolic Syndrome: A Randomized,Double-Blind,Placebo-Controlled Clinical Trial

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus −0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.