The safety and efficacy of IFN-beta products for the treatment of multiple sclerosis

Multiple sclerosis, a chronic demyelinating disease of the CNS, is now a treatable disease. Phase III clinical trials of three recombinant IFN-beta products conducted in relapsing-remitting multiple sclerosis have shown, albeit modest, significant effects on relapses and short-term progression of disability, and a more substantial effect on MRI parameters. However, these effects do not correlate well with clinical disease activity or long-term disability. Overall, IFN-beta is safe and generally well tolerated, and reported adverse events were comparable between preparations. Systemic side effects can be effectively managed by dose escalation, use of an auto-injector and careful clinical monitoring.     

BMI, fat and muscle differences in urban women of five ethnicities from two countries

OBJECTIVE: To investigate body composition differences, especially the relationship between body mass index (BMI) and percent body fat (%BF), among five ethnic groups. DESIGN: Cross-sectional. SUBJECTS: Seven hundred and twenty-one apparently healthy women aged 18-60 years (BMI: 17.4-54.0 kg/m(2)) from South Africa (SA, 201 black, 94 European) and New Zealand (NZ, 173 European, 76 Maori, 84 Pacific, 93 Asian Indian). MEASUREMENTS: Anthropometry, including waist circumference, and total, central and peripheral body fat, bone mineral content and total appendicular skeletal muscle mass (ASMM) derived from dual X-ray absorptiometry. RESULTS: Regression analysis determined that at a BMI of 30 kg/m(2), SA European women had a %BF of 39%, which corresponded to a BMI of 29 for SA black women. For a BMI of 30 kg/m(2) in NZ Europeans, equivalent to 43% body fat, the corresponding BMIs for NZ Maori, Pacific and Asian Indian women were 34, 36 and 26 kg/m(2), respectively. Central fat mass was lower in black SA than in European SA women (P<0.001). In NZ, Pacific women had the lowest central fat mass and highest ASMM, whereas Asian Indian women had the highest central fat mass, but lowest ASMM and bone mineral content. CONCLUSIONS: The relationship between %BF and BMI varies with ethnicity and may be due, in part, to differences in central fatness and muscularity. Use of universal BMI or waist cut-points may not be appropriate for comparison of obesity prevalence among differing ethnic groups, as they do not provide a consistent reflection of adiposity and fat distribution across ethnic groups.     

Implementation and evaluation of peer assessment of clinical skills for first year student nurses

Enabling student nurses to learn and develop evidence-based clinical skills is the cornerstone of nursing education programmes. This article describes the implementation of a peer assessment scheme for clinical skills within a skills laboratory in a university school of nursing, and the link between peer assessment and clinical skills development. This was a qualitative evaluative study that used questionnaires for data collection and was undertaken on one cohort of students. Findings showed that nearly half of all the statements made by students were about the positive impact of PACS on their skills learning. Students identified giving and receiving peer feedback, reflection and working with peers in small groups as being particularly valuable in clinical skills learning. Increased confidence was also a dominant finding as was the value of repeated practice in a simulation setting on skills development. This study supports some of the previous literature related to use of simulation and peer assessment but the discussion presented in this article also highlights that the findings of this study contradicts other findings in the literature. What makes this study unique is its contribution to the literature is the link that was established by students between the peer-assessment process and clinical skills learning.     

Hypothalamic pituitary adrenal axis and sympathetic activation: joint predictors of memory in children, adolescents, and adults

Although the links between physiological arousal and adults’ memory for emotional information are well understood, little is known about these links across development or when memory is examined for the actual event that induced arousal. In the current study, we examined the associations between physiological arousal and memory in children, adolescents, and young adults. Participants completed a laboratory stressor, the Trier Social Stress Test-Modified (TSST-M) during which salivary cortisol, pre-ejection period (PEP), and self-reported distress were measured. Two weeks later, participants completed a surprise memory test about what occurred during the TSST-M. Larger cortisol responses predicted enhanced memory, especially among individuals who also exhibited a PEP response the TSST-M. These associations did not vary with age. Results have implications for understanding how coordinated physiological responses may influence memory for salient, personal experiences across development.     

Cutaneous deciduosis: a report of two cases of an unusual pseudomalignancy

Cutaneous deciduosis represents a rare manifestation of cutaneous endometriosis in which typical endometrial glands and stroma are morphologically and physiologically transformed under hormonal influence. The transformed glands and stroma usually take on the microscopic appearance of uterine decidua but may mimic malignancy. We describe two cases of cutaneous deciduosis that presented in the post-partum period, but biopsies were not performed until a much later date. The first lesion arose on the perineum of a 31-year-old female after vaginal delivery, but a biopsy was not performed until 6 years after presentation. The second lesion grew in a cesarean section scar of a 26-year-old female with a history of ovarian adnexal endometriosis. Clinically described as a persistent post-operative hematoma, the lesion throbbed in synchrony with her menstrual cycles; a biopsy was also performed 6 years after presentation. Histopathologically, both specimens showed similar findings. Sections showed a multinodular proliferation of pale-staining epithelioid cells without significant nuclear atypia or conspicuous mitotic figures. Both showed focal glands that ranged from slit-like to slightly dilated and that contained a flattened epithelial lining without atypia. These unusual cases are presented to instruct about the pathologic findings of this entity in order to prevent the unnecessary diagnosis of malignancy. Natale KE, Royer MC, Rush WL, Lupton GP. Cutaneous deciduosis: a report of two cases of an unusual pseudomalignancy.     

Outcomes on the pharmacopsychometric triangle in bupropion-SR vs. buspirone augmentation of citalopram in the STAR*D trial

Bech P, Fava M, Trivedi MH, Wisniewski SR, Rush AJ. Outcomes on the pharmacopsychometric triangle in bupropion‐SR vs. buspirone augmentation of citalopram in the STAR*D trial. Objective: To compare within the framework of a novel pharmacopsychometric triangle, augmentation treatment with bupropion vs. buspirone in the acute therapy of major depression in the STAR*D study. The triangle provides a composite view in three domains of antidepressive activity, side effects, and quality of life. Method: Within the pharmacopsychometric triangle, the short six‐item subscales of the Hamilton Depression Scale (HAM‐D₁₇) and of the Inventory of Depressive Symptomatology (IDS‐C₃₀), referred to as HAM‐D₆ and IDS‐C₆, were focussed on pure antidepressive effect. Side‐effects (tolerable vs. intolerable) and quality of life were measured using patient‐administered questionnaires. A modified intention to treat sample was used. Results: Within the pharmacopsychometric triangle, bupropion‐SR (sustained release) was superior to buspirone when augmented to the current citalopram treatment. Thus, in the domain of pure antidepressive effect, bupropion‐SR was superior (P = 0.05) on the HAM‐D₆, IDS‐C₆, and IDS‐C₃₀, but not on the HAM‐D₁₇. In the domain of side effects, the total scores on the Patient Rated Inventory of Side Effects (PRISE) were reduced significantly more by bupropion‐SR than by buspirone (P = 0.03). In the domain of quality of life, the total scores on the Quality of Life Enjoyment and Satisfaction Questionnaire (QLES‐Q) showed a trend (P = 0.10) from baseline to endpoint of a superiority for bupropion‐SR compared with buspirone. Conclusion: In all domains of the pharmacopsychometric triangle, bupropion‐SR was superior to buspirone as augmentation therapy in depressed outpatients not responding to citalopram.     

Prediction of fat-free mass by bioimpedance analysis in migrant Asian Indian men and women: a cross validation study

BACKGROUND: Bioimpedance analysis (BIA) is a fast and convenient field technique for estimation of total body fat-free mass (FFM). However, bioimpedance-based prediction equations have been developed in predominantly white populations and little information is available on their usefulness in Asian Indian populations. OBJECTIVE: To develop a prediction equation for FFM based on BIA measurements applicable to a migrant population of Asian Indians and to investigate the predictive accuracy of published BIA-based equations in this ethnic group. DESIGN: FFM was measured by dual-energy X-ray absorptiometry in 211 healthy adults (110 men, 101 women; age ranges 19-74 year) of Asian Indian ethnicity and used as the reference measure to develop prediction equations based on single-frequency BIA measurements of resistance and reactance. A cross-validation technique was applied. Predictive accuracy of published BIA-based equations was assessed in this sample. RESULTS: Sex-specific equations developed in the entire group included height2/resistance and body weight as predictors (R2=0.84 and 0.70 and standard errors of estimate of 2.8 and 2.0 kg for males and females, respectively; CV: 6%). Of published equations examined, one predicted FFM satisfactorily in men with nonsignificant bias and may be applicable to Asian Indian populations. None of the published equations tested performed satisfactorily in women. CONCLUSIONS: Bioimpedance-based equations for predicting FFM developed specifically in Asian Indians are recommended for field studies designed to measure body composition of this ethnic group.     

A common phosphotyrosine signature for the Bcr-Abl kinase

The Bcr-Abl fusion kinase drives oncogenesis in chronic myeloid leukemia (CML). CML patients are currently treated with the Abl tyrosine kinase inhibitor imatinib, which is effective in early stages of the disease. However, resistance to imatinib arises in later disease stages primarily because of a Bcr-Abl mutation. To gain deeper insight into Bcr-Abl signaling pathways, we generated phosphotyrosine profiles for 6 cell lines that represent 3 Bcr-Abl fusion types by using immunoaffinity purification of tyrosine phosphopeptides followed by tandem mass spectrometry. We identified 188 nonredundant tyrosine-phosphorylated sites, 77 of which are novel. By comparing the profiles, we found a number of phosphotyrosine sites common to the 6 cell lines regardless of cellular background and fusion type, several of which are decreased by imatinib treatment. Comparison of this Bcr-Abl signature with the profile of cells expressing an alternative imatinib-sensitive fusion kinase, FIP1L1-PDGFRalpha, revealed that these kinases signal through different pathways. This phosphoproteomic study of the Bcr-Abl fusion kinase highlights novel disease markers and potential drug-responsive biomarkers and adds novel insight into the oncogenic signals driven by the Bcr-Abl kinase.     

Human papillomavirus prevalence in women who have and have not undergone hysterectomies

We compared human papillomavirus (HPV) prevalence in an age-stratified random sample of women who have undergone a hysterectomy (WH) (n=573) with the HPV prevalence in age-matched women with intact cervices (women who have not undergone a hysterectomy [WNH]) (n=581) participating in a study at Kaiser Permanente in Portland, Oregon. Testing cervicovaginal lavage fluids for >40 HPV genotypes using an MY09/11 L1 consensus primer polymerase chain reaction method, we found no statistical differences in the prevalence of HPV (16% for WNH vs. 13.9% for WH) or carcinogenic HPV (6.5% for WNH vs. 4.5% for WH) between the 2 groups of women. Although WH have a similar prevalence of carcinogenic HPV infection, compared with WNH without a cervix, they have minimal risk of HPV-induced cancer and are unlikely to benefit from HPV testing.