Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.     

Who will conceive with IVF?

When considering the chances of establishing a healthy ongoing pregnancy after in vitro fertilization (IVF), the cause of infertility plays a relatively minor role. In recent years, there has been a shift from determining the diagnosis to the individual prognosis for a given patient. A number of prognostic factors were identified, which enabled clinicians to appropriately counsel patients. Patient-determined factors are of crucial importance and some are amenable to intervention such as lifestyle and nutritional advice. However, the attention of clinicians remains on seeking adjuvant therapeutic interventions designed to improve the outcomes of IVF treatment. In this article, the patient-determined factors underlying the individual chance of conceiving and the more commonly prescribed empirical medical therapies prescribed to enhance outcomes are reviewed. It is concluded that greater attention to optimizing the health of the couple before starting IVF treatment may be more beneficial than adjuvant medical therapies during treatment.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

A Comparison of adults with antisocial personality traits with and without childhood conduct disorder.

BACKGROUND: Antisocial personality disorder (ASPD) in DSM-IV is unique among personality disorder diagnoses in requiring the individual to satisfy a number of childhood criteria in addition to relevant traits exhibited in adulthood. We examined the validity of this childhood requirement. METHODS: Personality disordered individuals assessed using the International Personality Disorder Examination and exhibiting a sufficient number of adult antisocial traits to meet criterion A of DSM-IV were subdivided into those who exhibited antisocial traits in both adulthood and childhood and those who had such traits in adulthood only. The two groups were then compared on a number of historical, clinical, and self-report measures. RESULTS: Thirty individuals meeting both childhood and adult criteria (ASPD) were compared with 39 meeting adult antisocial criteria only (ASS). Few differences were found between the two groups on the measures examined, although those in the ASPD group appeared more severe and had higher anger scores on the STAXI-2 psychometric test. CONCLUSIONS: This failure to find clinically important differences between the two groups is in agreement with previous reports and needs to be taken into account in future revisions of ASPD in DSM.     

Predictors of incident depression after hip fracture surgery.

OBJECTIVE: Depression after hip fracture surgery is prevalent and associated with increased mortality rates and impaired functional recovery. The incidence of new-onset depressive symptoms in patients initially not depressed after hip fracture surgery and their relationship with functional recovery is unknown. METHODS: A cohort of 139 nondepressed elderly patients (>60 years) hospitalized for hip fracture surgery were followed up for six months. Clinically significant depressive symptoms were defined as a score of 7 or more on the 15-item Geriatric Depression Scale. RESULTS: The authors found a cumulative incidence rate of 20.5% adjusted for dropouts. Multiple Cox-regression analyses yielded the presence of subthreshold symptoms of depression, anxiety, pain, and cognitive impairment at baseline, the premorbid level of mobility, and a history of (treated) depression as risk factors for incident depression (p <0.05). A forward, conditional procedure identified postoperative pain (hazard ratio [HR] = 1.32, 95% confidence interval [CI]: 1.14-1.53, Wald chi(2) = 13.57, df = 1, p <0.001) and baseline anxiety (HR = 1.25, 95% CI: 1.08-1.44, Wald chi(2) = 8.86, df = 1, p = 0.003) as the strongest independent risk factors. Incident depression was associated with a less favorable outcome at 3 months follow-up. CONCLUSION: This exploratory study identified two treatable baseline characteristics that predicted incident depression in nondepressed patients after hip-fracture surgery.     

The public health and brief interventions for excessive alcohol consumption: The british experience

Widely disseminated brief interventions against excessive drinking, as part of the new public health movement, have a potentially crucial role in reducing alcohol-related harm on a national scale. However, a number of conceptual problems and practical barriers to progress in this area can already be identified. This article focuses on the British experience of research and implementation of community-based brief interventions, which is longer than that of other countries, as a means of discussing these problems. Rather than being pessimistic about the possible impact of brief interventions, the article is based on the assumption that it is only by clearly recognizing and solving such problems that the potential of brief interventions in the alcohol field will be fully realized.     

Is there a relationship between attention deficit hyperactivity disorder and bipolar disorder?

With the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a relationship between bipolar disorder (BP) and ADHD has attracted growing interest. This paper critically reviews the scientific literature concerning this postulated relationship by examining evidence from clinico-epidemiological, follow up, family and laboratory studies, including neuroimaging, neuropsychology and genetic studies. The evidence suggests that although the diagnostic categories of BP and ADHD appear to be unrelated, there is support for a possible relationship between some ADHD and manic-like symptoms. However, several fundamental methodological issues require rectification in future research in order to further elucidate the relationship between these disorders.