Models of breast cancer: is merging human and animal models the future?

Survival rates of patients with early breast cancer in the United Kingdom and in the United States have improved steadily over the past 15 years. The only way to continue or even accelerate this progress, however, is the discovery and development of new preventative and therapeutic strategies. With the massive explosion in potential therapeutic strategies becoming available, in the postgenomic era, better and more representative breast cancer models are urgently required for preclinical trials.

Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study.

Background: Isoflavones are estrogen-like plant compounds that may protect against cardiovascular disease and endocrine-responsive cancer. Isoflavones may, because of their ability to act as selective estrogen receptor modulators, alter insulin-like growth factor (IGF) status.

Objective: The aim of this study was to assess the effect of 1-month isoflavone supplementation (86 mg/day red clover-derived isoflavones) on IGF status.

The renin-angiotensin system and physical performance.

Many of us recognize that some individuals seem "gifted" in sporting ability. We may also have noted the association of such elite performance with past parental success, recognizing intuitively the role of inherited traits. With the expansion of molecular biology and associated technologies, we now find ourselves better able to explore these genetic influences.

Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons.

Protein expression and de novo synthesis in normal and prostate cancer cell lines derived from the same patient were compared by proteomic analysis, and the effects of INFalpha and INFgamma (INF=interferon) determined. The expressions of several INF-inducible proteins, including MxA, Nmi, PA28a and IFP53, were downregulated in the cancer cells. INFgamma induced a more than twofold increase or decrease in the synthesis rates of almost twice as many proteins in the cancer cell line.

Socioeconomic gradient in body size and obesity among women: the role of dietary restraint, disinhibition and hunger in the Whitehall II study.

Objective: To examine the associations between three psychological eating behaviour variables--restraint, hunger and disinhibition--and body weight and size, and to assess their explanatory power for the employment grade gradients in body measurement.

Design: Cross-sectional analysis of self-report and clinical data.

Subjects: : In all, 1470 women (aged 45-68 y, mean 56.

Misoprostol and pregnancy: ever-increasing indications of effective usage.

Purpose Of Review: The subject of misoprostol in the field of reproductive health care has courted much controversy. The aim of this review is to survey the literature published in this field over the past year, and to evaluate developments in this area. This article will cover termination of pregnancy, induction of labor and the issue of postpartum hemorrhage.

The role of metformin in the management of polycystic ovary syndrome.

Purpose Of Review: The purpose of this review is to provide a critical summary of recent studies on the clinical effects of metformin in polycystic ovary syndrome.

Recent Findings: After the recognition that hyperinsulinaemia is a fundamental disturbance in polycystic ovary syndrome, a novel and promising form of therapy in the form of insulin-sensitizing drugs has been introduced. Among these, metformin is the most widely used.

Chemical and microbiologic aspects of penems, a distinct class of beta-lactams: focus on faropenem.

Many beta-lactam antimicrobials were developed between the 1960s and 1980s, with continuing development driven by the emergence of microbial resistance. Penems form a discrete class of beta-lactams that comprises structural hybrids of penicillins (penams) and cephalosporins (cephems). The chemistry and microbiology of the representative penems MEN 10700, ritipenem, CGP 31608, sulopenem, BRL 42715, and faropenem are reviewed.

What do we know about hospital at home? Lessons from international experience.

Hospital in the home' or 'hospital at home' services have become popular solutions to the apparent problems of conventional hospital care in many countries. Until recently their evaluation has been limited, and little has been known about their costs and benefits. A systematic review of randomised controlled trials of such services has failed to detect a difference in mortality and readmission rates of patients using hospital in the home, but does suggest that these services are acceptable to patients, although not necessarily to their carers.

Bradykinin receptor gene variant and human physical performance.

Accumulating evidence suggests that athletic performance is strongly influenced by genetic variation. One such locus of influence is the gene for angiotensin-I converting enzyme (ACE), which exhibits a common variant [ACE insertion (I)/deletion (D)]. ACE can drive formation of vasoconstrictor ANG II but preferentially degrades vasodilator bradykinin.

Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines.

Adoptive transfer of CMV-specific T cells offers the potential for reconstitution of viral immunity after allogeneic transplantation. However, the logistics of producing virus-specific T-cell clones has limited the application of cellular therapies. We treated 16 patients for CMV infection with polyclonal CMV-specific T-cell lines generated by short-term culture.

Making sense of symptom checklists: a latent class approach to the first 9 years of the British Household Panel Survey.

Background: In health inequalities research there is a growing impetus to examine the development of inequalities in health over time. However, many of the sources of longitudinal data in Britain are not designed specifically for health research. Typically, health status is assessed by self-reported problems and the use of symptom checklists.

Physiological implications of the materno-fetal oxygen gradient in human early pregnancy.

This study evaluates the role of the fetal fluid cavities on materno-fetal oxygen diffusion in early pregnancy. Oxygen tension (pO2) was recorded using a multiparameter sensor inserted inside the exocoelomic cavity (ECC) or in the amniotic cavity. There was no correlation between coelomic pO(2) and gestational age, but a negative correlation was found between amniotic pO(2) and gestational age.

The effect of enterocystoplasty on bone strength assessed at four different skeletal sites in a rat model.

The objective of the study was to investigate bone strength at four different skeletal sites in a chronic animal model of urinary diversion. Young male Wistar rats (120) were allocated randomly to four groups undergoing ileocystoplasty; ileocystoplasty and resection of the ileocecal segment; colocystoplasty; or sham operation (controls). After 8 months the lumbar vertebrae, femora, and tibiae were harvested at necropsy.

Obstetric outcome after threatened miscarriage with and without a hematoma on ultrasound.

Objective: To examine the effect of threatened miscarriage on second-trimester maternal serum alpha-fetoprotein (MSAFP) levels and pregnancy outcome; and to study the significance of ultrasound evidence of an intrauterine hematoma on pregnancy outcome in these patients.

Methods: A retrospective, case-control study was performed on 144 women presenting with bleeding in the first trimester and 144 age-matched control subjects who attended for routine dating scans during the same time scale. The presence or absence of an intrauterine hematoma, MSAFP, and pregnancy outcomes were recorded.

A life course approach to assessing causes of dental caries experience: the relationship between biological, behavioural, socio-economic and psychological conditions and caries in adolescents.

The objective of this study was to further elucidate the relationship between relevant biological, behavioural, socio-economic and psychological conditions, experienced in very early life and along the life course, and dental caries experience using the life course approach. A two-phase study was carried out in Brazil. In the first phase, 652 13-year-olds were clinically examined and interviewed.

Percutaneous ultrasound-guided injection of the trachea in fetal sheep: a novel technique to target the fetal airways.

Objective: To access the fetal airways percutaneously using ultrasound-guided injection of the fetal trachea in sheep.

Methods: Adenoviral gene therapy vectors and transduction-enhancing agents were delivered to the trachea via a needle inserted through the thorax or the neck of late-gestation (0.9 term, n = 3) or mid-gestation (0.

Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model.

Objective: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.

Materials And Methods: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics.

Management of uncontrolled hypertension in a nurse-led clinic compared with conventional care for patients with type 2 diabetes.

Objective: To compare the effectiveness of a nurse-led hypertension clinic with conventional community care in general practice in the management of uncontrolled hypertension in patients with type 2 diabetes.

Research Design And Methods: We studied 120 men and women outpatient attendees (61% non-Caucasian) with type 2 diabetes and a seated blood pressure (BP) >or=140/80 mmHg. All patients were being treated for hypertension, and 71% had increased urinary albumin excretion (UAE).

Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X2 receptor subunit.

ATP is involved in central respiratory control and may mediate changes in the activity of medullary respiratory neurones during hypercapnia, thus playing an important role in central chemoreception. The main objective of this study was to explore further the role of ATP-mediated signalling in respiratory control and central chemoreception by characterising the profile of the P2X receptors expressed by physiologically identified respiratory neurones. In particular we determined whether respiratory neurones in the rostral ventrolateral medulla (VLM) express P2X2 receptor subunits of the ATP-gated ion channel, since ATP currents evoked at recombinant P2X2 receptors are potentiated by lowering extracellular pH.

Prognostic implications of the presence of FLT3 mutations in patients with acute myeloid leukemia.

Several studies have shown that mutations in the FLT3 gene are common events in AML, with approximately one third of adult patients harbouring either an internal tandem duplication in the juxtramembrane domain or a D835 mutation in the kinase domain. The majority of studies in pediatric and adult AML have shown that FLT3 mutations are powerful prognostic factors predicting for increased relapse risk and adverse overall survival. Some reports have suggested that loss of the wild type allele might be associated with an even worse prognosis.

The human first trimester gestational sac limits rather than facilitates oxygen transfer to the foetus--a review.

Oxygen (O2) free radicals are a potential teratologic threat to the foetal tissues and are known to be involved in the pathophysiology of common human pregnancy disorders such as miscarriage and pre-eclampsia. During the first two months of human gestation, the placenta surrounds the whole gestational sac, the villi contain only a few capillaries located mainly within the centre of the mesenchymal core, the trophoblastic layer is twice the thickness it will be in the second trimester, the foetal red cells are nucleated and the exocoelomic cavity (ECC) occupies most of the space inside the gestational sac. The ECC contains no oxygen transport system, but anti-oxidant molecules that may provide additional protection to the embryo from oxidative damage are present.