The value of the Van Nuys Prognostic Index in ductal carcinoma in situ of the breast: a retrospective analysis

The Van Nuys Prognostic Index 1996 (VNPI), based upon tumor size, pathological grade and tumor margins, is a guideline for the treatment of ductal carcinoma in situ (DCIS). It was thought to strongly decrease overtreatment. In 2003, age was added to the index as a fourth prognostic factor. We examined changes in treatment modality after applying the VNPI retrospectively and investigated if the addition of age to the Index causes a shift in treatment. The influence of each prognostic factor on disease-free survival (DFS) was calculated. We performed a retrospective file study of DCIS patients treated between 1985 and 2003 at the University Hospital, Antwerp. Patients were assigned a Van Nuys Score 1996 and 2003. The influence of tumor size, pathological grade, tumor margins and age on DFS was calculated with the Kaplan-Meier method and the log-rank test. We identified 104 DCIS cases with a median follow-up of 36 months. Twelve patients showed recurrence (11.5%), of whom seven were invasive (58%). Seventeen of the 29 women diagnosed before 1997 were undertreated according to the VNPI 1996 and six of them showed recurrence. The remaining three recurrences were correctly treated. Seventy-five patients diagnosed after 1997 were all treated according to the VNPI 1996 and only three had a recurrence. The introduction of age caused no significant shift in treatment modalities. Significant differences in DFS were seen between large (>41 mm) and small (<15 mm) tumors (p = 0.0074), old (>60 years) and young (<40 years) patients (p = 0.024) and Van Nuys Subgroup 2 and 3 (p = 0.04). Tumor margins and pathological grade showed no significant difference in DFS. The VNPI can be a useful tool in the treatment of DCIS. However, this Index is not evidence-based, using a relatively small retrospective series of patients. The validity of the modified VNPI must be prospectively confirmed with large numbers of DCIS patients.     

Identification of epigenetically silenced genes in tumor endothelial cells

Tumor angiogenesis requires intricate regulation of gene expression in endothelial cells. We recently showed that DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors directly repress endothelial cell growth and tumor angiogenesis, suggesting that epigenetic modifications mediated by DNMTs and HDAC are involved in regulation of endothelial cell gene expression during tumor angiogenesis. To understand the mechanisms behind the epigenetic regulation of tumor angiogenesis, we used microarray analysis to perform a comprehensive screen to identify genes down-regulated in tumor-conditioned versus quiescent endothelial cells, and reexpressed by 5-aza-2'-deoxycytidine (DAC) and trichostatin A (TSA). Among the 81 genes identified, 77% harbored a promoter CpG island. Validation of mRNA levels of a subset of genes confirmed significant down-regulation in tumor-conditioned endothelial cells and reactivation by treatment with a combination of DAC and TSA, as well as by both compounds separately. Silencing of these genes in tumor-conditioned endothelial cells correlated with promoter histone H3 deacetylation and loss of H3 lysine 4 methylation, but did not involve DNA methylation of promoter CpG islands. For six genes, down-regulation in microdissected human tumor endothelium was confirmed. Functional validation by RNA interference revealed that clusterin, fibrillin 1, and quiescin Q6 are negative regulators of endothelial cell growth and angiogenesis. In summary, our data identify novel angiogenesis-suppressing genes that become silenced in tumor-conditioned endothelial cells in association with promoter histone modifications and reactivated by DNMT and HDAC inhibitors through reversal of these epigenetic modifications, providing a mechanism for epigenetic regulation of tumor angiogenesis.     

The Role of Academia in Community-Based Pharmaceutical Care

Developing models of pharmaceutical care (PC) for educating students and practitioners represents a fundamental role for schools of pharmacy. Virginia Commonwealth University has sought to facilitate the implementation of PC in the community by hiring faculty to practice in this setting. The mission of the faculty is to implement PC in a community pharmacy practice, to develop clerkship sites for Pharm.D. students, and to evaluate the impact of PC services in the community. Examples of an independent pharmacy model, a grocery chain model, and a retail chain model of care may serve a dual purpose for faculty members, that is, define responsibilities for the academic institution and for the community practice environment.     

Pulmonary alveolar proteinosis: two contrasting cases.

Pulmonary alveolar proteinosis is a rare condition characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. Two cases with contrasting modes of presentation, course, and response to therapeutic whole lung lavage are described. Both cases were in hypoxaemic respiratory failure at the time the definitive diagnosis was made, and in both cases the diagnosis was made by segmental bronchoalveolar lavage following negative open lung biopsy. In neither was an underlying causative organism or agent identified. In one case the alveolar proteinosis developed in late pregnancy, a presentation that is previously unreported. Clinical improvement in this case required repeated whole lung lavages and was accompanied by a trend towards normalization of the ratios of surfactant protein-A and surfactant protein-B to disaturated phospholipid, ratios which may be useful as prognostic indicators. The response to therapeutic lavage was markedly different in the two cases, and it is postulated that this may relate to the fact that alveolar proteinosis is a heterogeneous disease and that the course and response to treatment may relate in part to the specific composition of the abnormal proteinaceous fluid.     

Free moment contribution to quiet standing in able-bodied and scoliotic girls

Adolescent idiopathic scoliosis girls are known to display standing imbalance. In addition to a motor deficit problem, the axial torsion of the spine and trunk torsion could reflect an imbalance around the vertical axis. Unlike the excursion of the center of pressure (COP), the forces and moments were rarely addressed to characterize the quiet standing balance. Nonetheless, one dynamical parameter, called free moment (T _V), representing the vertical torque on the feet can reflect the oscillation around the vertical axis associated to the standing imbalance. The objectives of this study were to test if the free moment variability can be utilized to characterize standing balance in a group of able-bodied and non-treated scoliotic girls and to determine if it was associated with that of the COP among each group of subjects tested. Forty-six adolescent girls with half of them presenting an adolescent idiopathic scoliosis were tested during quiet standing balance. Standing balance was assessed with the subjects standing upright and bare feet on a force plate. RMS and range of COP excursions and free moment were calculated.The scoliotic group displayed higher variability in COP excursion by about 24% than the able-bodied girls. Similarly, the T _V RMS (P = 0.00136) and range (P = 0.00197) were statistically higher by about 42% in the scoliotic group. The variability of T _V was associated with that of the COP in both groups. In the medio-lateral direction, the significant correlations between the RMS and range of the free moment and those of the COP were about 0.7 for the able-bodied group and 0.5 for the medio-lateral COP range for the scoliotic group girls. Along the antero-posterior axis, the only statistically significant correlations were observed for the scoliotic group. The free moment variability about the COP measured during quiet standing can be suggestive of an asymmetry control of the trunk around the vertical axis during standing balance. Its variability was more pronounced in scoliotic girls and was associated with the antero-posterior COP variability reflecting both biomechanical and motor control deficits. Free moment calculation could be a supplement insight into the standing balance of scoliotic subjects.     

Production of a novel influenza vaccine using insect cells: protection against drifted strains

A recombinant trivalent hemagglutinin (HA) vaccine produced in cell culture using the baculovirus expression system provides an attractive alternative to the current egg‐based influenza vaccine (Trivalent Inactivated Influenza Vaccine [TIV]) manufacturing process. The HA genes from the annual World Health Organization‐recommended strains are cloned, expressed, and purified using a general purification process. Here, we provide an overview of the expression technology used to make the annual adjustment of the vaccine and the clinical studies completed to date with recombinant HA. The highly purified protein vaccine, administered at three times higher antigen content than TIV, results in stronger immunogenicity, a long‐lasting immune response and provides cross‐protection against drift variant influenza viruses. Furthermore, the vaccine does not contain egg proteins, adjuvants, preservatives, endotoxins, or antibiotics and can therefore be used in a broader population.     

Perceived sources of stress among student nurses.

Questionnaire data was collected from a sample of 306 student nurses from three institutions (university, college of advanced education and hospital) during the second week of the first year of their course, and from 189 students from two of the institutions (university and CAE) at the conclusion of their first year of education. The main sources of stress on both occasions were essentially the same for women and men, and for students from the different institutions. These concerns focussed on study-related issues, the emotional demands of nursing, the use of technical equipment, interpersonal interaction, and lack of time for family and personal pursuits. It was suggested that these concerns could be reduced through the introduction of education in study skills, the provision of the opportunity to gain hands-on experience with technical equipment, and the development of social skills.     

The treatment of chronic pain in Québec: a study of hospital-based services offered within anesthesia departments

PURPOSE: Little or no information exists on the services that are currently available for the treatment of chronic pain across the different regions of Canada. As a first step, this study documented the hospital-based resources and services offered for the management of chronic non-cancer pain within anesthesia departments in Québec. METHODS: In collaboration with the Association of Anesthesiologists of Québec and the Société québécoise de la douleur, a provincial survey was conducted to assess the availability of services for chronic pain management within hospital-based anesthesia departments along with the volume of clinical activities, staff composition, treatments offered and space facilities. RESULTS: The response rate was 100%. Fifty of the 69 departments (73%) offered services for the management of chronic non-cancer pain but the services were often limited. Twenty-six percent (13/50) of the departments provided some form of multidisciplinary assessment and treatment but only three had a core team comprised of an anesthesiologist, a nurse, a psychologist, and a physical therapist. Examination of patient waiting lists of the surveyed departments revealed disturbing results: approximately 4,500 patients were waiting for their first appointment to see a pain consultant, and nearly 3,000 (67%) had been waiting for nine months or more. CONCLUSION: Although this survey did not include the services offered in departments other than anesthesia, the results show the extent to which the province of Québec is under-resourced for the management of chronic pain patients both in terms of access to treatment and quality of the services offered.     

Trends in hospital admissions and mortality from asthma and chronic obstructive pulmonary disease in Australia, 1993-2003

OBJECTIVE: To examine evolving changes in asthma and chronic obstructive pulmonary disease (COPD) in South Australia and Australia as a whole from the perspective of hospital admissions, ventilatory support and mortality data. DESIGN: Retrospective analyses, for the period 1993-2003, of hospital separations data from the Australian Institute of Health and Welfare and the Integrated South Australian Activity Collection, and mortality data from the Australian Bureau of Statistics and South Australian hospital morbidity collection. MAIN OUTCOME MEASURES: Hospital separations, ventilatory support episodes, mortality rates, burden-of-disease rankings. RESULTS: Between 1993 and 2003, in SA and nationally, hospital separations for asthma declined but separations for COPD increased significantly. Falling mortality rates from asthma in both men and women, and from COPD in men, contrast with increasing rates of COPD-related hospitalisation and mortality in women. CONCLUSIONS: Hospital admissions and mortality associated with asthma have fallen. Admission rates for COPD are declining for men, but there is no indication that admission rates for women have reached a peak. There is a need for higher prioritisation of COPD, including policies to reduce smoking in women, and medical practice initiatives to support primary and secondary prevention, pulmonary rehabilitation and appropriate drug therapies.