The genetic and epigenetic basis of ependymoma

Introduction  

Although ependymoma is the third most common pediatric brain tumor, we know little about the genetic/epigenetic basis of its initiation, maintenance, or progression. This is due in part to the heterogeneity of the disease, as well as the small sample size of the cohorts analyzed in most studies.     

Abnormal fluorine-18-fluorodeoxyglucose uptake in benign esophageal leiomyoma

A benign esophageal leiomyoma with abnormally increased fluorine-18-fluorodeoxyglucose uptake on positron emission tomography (PET) was resected thoracoscopically. The tumor, of which the maximum standardized uptake value of the lesion was 4.7, was well defined and 38 mm in diameter. Neither mitotic activity nor degeneration was found histologically; and immunoreactivity for CD34, CD117, MIB-1, and glucose transporter-1 was negative immunohistochemically. A diagnosis of gastrointestinal stromal tumor was ruled out by an oncogenic kinase gene mutation study. This case cautions against PET-dependent evaluation for malignant potential of esophageal submucosal tumors.     

Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder     

How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.     

The role of gender in an obstetrics and gynecology residency program

A brief historical review of the role of female medical students and female physicians in American medicine is presented. The 1985-1986 Council on Resident Education in Obstetrics and Gynecology Residency Data Bank was analyzed for gender distribution. Questionnaire studies were undertaken to study the possible effect of the increasing number of female residents in an obstetrics and gynecology residency program. Queries were sent to current and former residents, the attending staff, and the nursing and anesthesiology staffs. In order to evaluate the national scene, letters were mailed to directors of programs with 20 or more residents. The overall results indicated female residents have a positive effect on residency training.     

The Bradykinin-potentiating peptides from venom gland and brain of Bothrops jararaca contain highly site specific inhibitors of the somatic angiotensin-converting enzyme

Pyroglutamyl, proline-rich oligopeptides, classically referred to as bradykinin-potentiating peptides (BPPs) are found in Bothrops jararaca venom, and are naturally occurring inhibitors of the somatic angiotensin-converting enzyme (ACE). The chemical and pharmacological properties of these peptides were essential for the development of captopril, the first active site directed inhibitor of ACE, currently used to treat human hypertension. ACE is a complex ectoenzyme of the vascular endothelium, possessing two catalytic sites, performing diverse specific roles. Recent advances concerning novel features of BPPs revealed that they might still contribute to a better understanding of the cardiovascular physiology and pathology. The molecular biology of the BPPs revealed that they are part of two distinct C-type natriuretic peptide precursors found in the venom gland and the brain of B. jararaca, each containing seven BPPs. In situ hybridization studies detected the presence of the corresponding mRNA precursor in snake brain regions correlated with neuroendocrine functions, such as the ventro-medial hypothalamus, the paraventricular nuclei, the paraventricular organ, and the subcommissural organ. In this article we discuss the large variety of homologous BPPs in B. jararaca venom and brain, its significance, and whether the BPPs could represent novel endogenous neuropeptides.