Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism. The protein (FMRP) encoded by the fragile X mental retardation gene (FMR1), is an RNA-binding protein linked to translational control. Recently, in the Fmr1 knockout mouse model of FXS, dysregulated translation initiation signaling was observed. To investigate whether an altered signaling was also a feature of subjects with FXS compared to typical developing controls, we isolated total RNA and translational control proteins from lymphocytes of subjects from both groups (38 FXS and 14 TD). Although we did not observe any difference in the expression level of messenger RNAs (mRNAs) for translational initiation control proteins isolated from participant with FXS, we found increased phosphorylation of the mammalian target of rapamycin (mTOR) substrate, p70 ribosomal subunit 6 kinase1 (S6K1) and of the mTOR regulator, the serine/threonine protein kinase (Akt), in their protein lysates. In addition, we observed increased phosphorylation of the cap binding protein eukaryotic initiation factor 4E (eIF4E) suggesting that protein synthesis is upregulated in FXS. Similar to the findings in lymphocytes, we observed increased phosphorylation of S6K1 in brain tissue from patients with FXS (n = 4) compared to normal age-matched controls (n = 4). Finally, we detected increased expression of the cytoplasmic FMR1-interacting protein 2 (CYFIP2), a known FMRP interactor. This data verify and extend previous findings using lymphocytes for studies of neuropsychiatric disorders and provide evidence that misregulation of mTOR signaling observed in the FXS mouse model also occurs in human FXS and may provide useful biomarkers for designing targeted treatments in FXS.

Case report. Efficacy of Hoodia for weight loss: is there evidence to support the efficacy claims?

Increasing rates of adult obesity and its negative health consequences are likely to become an increasing burden to the Canadian health care system. Consumers are looking for treatment options and often try the natural health products that are heavily promoted as safe, fast and effective. In this case report, MH, a 57-year-old overweight female wanted advice regarding whether she should use the natural product Hoodia to help her attain her weight loss goals. A literature search was conducted using Medline, EMBASE, the Cochrane Library, Natural Medicines Comprehensive Database and IPA from inception to March 2009. The internet, files of the authors and bibliographies of articles were searched for additional references. No published, peer-reviewed randomized controlled trials examining efficacy of Hoodia were found. Unpublished data from two small trials reported promising results with no adverse events. However, this leaves many unanswered questions regarding the use of Hoodia for weight loss such as the appropriate dose and duration, short and long term safety and use in patients with concomitant diseases. Literature suggests that some commercial products may not actually contain Hoodia at all. Additionally, Hoodia is not yet listed in the Canadian Licensed Natural Health Products Database meaning products sold in Canada may not meet Canadian regulatory standards. Upon discussing this information, MH decided not to use Hoodia, and other evidence-based recommendations were discussed.

The impact of socioeconomic and demographic factors on the utilization of smoking cessation medications in patients hospitalized with cardiovascular disease in Nova Scotia, Canada.

OBJECTIVE: To determine whether any demographic or socioeconomic factors affect the use of smoking cessation medications in patients hospitalized with heart disease. METHOD: Data were obtained from the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) Canada database, which includes a registry of all hospitalized patients with a diagnosis of ischaemic heart disease, congestive heart failure, or atrial fibrillation since October 1997. Patients agreeing to provide follow-up were sent an enrollment survey to determine demographic and socioeconomic factors including household income, educational background and private drug insurance plans. RESULTS: Between 15 October 1997 and 31 December 2000, 5442 patients who were current smokers and 270 patients using a smoking cessation medication were admitted to hospital registered in the ICONS database. An enrollment survey was completed by 1071 current smokers and 77 patients using a smoking cessation agent. CONCLUSION: Higher education level, presence of private drug insurance plans, and less difficulty paying for basic needs were associated with higher use of smoking cessation medications.

Development of a Canadian family medicine pharmacy practice experience programme.

Faculties of Pharmacy in Canada must currently provide students with at least 16 weeks of structured pharmacy practice experience. In recent years, the College of Pharmacy at Dalhousie University in Halifax, Nova Scotia, Canada has been developing more practice experience sites in non-institutional settings. One of these is at the Department of Family Medicine at Dalhousie University. This paper describes the development and expansion of clinical pharmacy services in the Family Medicine Clinics, provided by one of the College's clinical faculty members. With those services in place, the clinical pharmacist was ready to begin precepting pharmacy students at the Family Medicine Clinics. A proposal for a family medicine pharmacy practice experience programme was written, accepted and piloted in 1994-95. Following the success of that initial trial, the programme has continued and expanded over the years. Evaluation from the programme participants indicates that experience allows the pharmacy student to successfully complete programme objectives and gain an appreciation for working with other health care professionals to optimize patient care. The Family Medicine Clinics also appreciate the contributions made by the pharmacy students and value the interaction between students training in pharmacy and residents in family medicine.

Physician characteristics in relation to cardiovascular drugs commonly prescribed for hypertension in Nova Scotia.

BACKGROUND: Cardiovascular drugs are the most frequently prescribed class of drugs in Canada. Among them, drugs used to treat hypertension are the single largest component. Variability in how these drugs are prescribed should be based on the specific characteristics of patients. However, some evidence shows that physician characteristics can also play a substantial role in prescribing trends. Such variation is also associated with varying beneficial and adverse patient outcomes. PURPOSE: To determine whether prescribing patterns of drugs used to treat hypertension in elderly patients in Nova Scotia varied by physician characteristics. METHODS: A retrospective, population-based descriptive study was done using the Nova Scotia Pharmacare program data for the fiscal year 1995/96. The unit of analysis was the individual physician. All drugs indicated in the management of hypertension were included for the analysis. RESULTS: Of 1466 physicians included in the analysis, 1004 were family physicians (FPs) and/or general practitioners (GPs), 155 were internal medicine specialists and 307 were other specialists. Fifty-eight per cent of 103,193 eligible senior citizens received at least one of the study medications. FPs and/or GPs prescribed 95.9% of all the study drugs. Internists prescribed proportionately fewer angiotensin-converting enzyme inhibitors, thiazides and other diuretics compared with the FPs and/or GPs but more beta-blockers and calcium channel blockers. A large proportion of the FPs and/or GPs (55.3%) prescribed less than 10% of the total day's supply of drugs, whereas a small proportion of FPs and/or GPs (16.3%) prescribed 52.6% of all the study drugs. There was no variation in the distribution of the types of antihypertensives prescribed based on physician age, sex or volume of prescribing. A slight variation in prescribing was seen with location of practice. CONCLUSIONS: Patterns of prescribing cardiovascular drugs used to treat hypertension were remarkably unaffected by physician characteristics. This finding counters other evidence in the literature that has raised concerns over prescribing patterns of certain types of physicians. Prescribing patterns may vary for other drug classes, but for this group of antihypertensives, little variability was found.

Pharmacy services in family medicine residencies. Survey of clinics associated with Canadian residency programs.

Surveys were mailed to 82 family medicine clinics associated with residency programs in Canada to ascertain the extent, if any, of pharmacy involvement in the programs. Eight of the 58 (13.8%) usable returns had pharmacists directly involved. They provided pharmacy-based services, offered clinical services, and participated in research.

The effect of aspirin on niacin-induced cutaneous reactions.

BACKGROUND: Niacin (nicotinic acid) is one of the first-line agents recommended for the treatment of hyperlipidemia. Bothersome cutaneous reactions (flushing, feeling of warmth, itching, and tingling), however, often limit patient acceptability and tolerability. The National Cholesterol Education Program recommends giving aspirin or another nonsteroidal anti-inflammatory drug before administering niacin. Lack of scientific data supporting this recommendation, however, led to this randomized, double-blind, placebo-controlled trial to evaluate the efficacy of 80 mg of aspirin and 325 mg of aspirin in reducing these cutaneous reactions. METHODS: Thirty-one healthy subjects were randomized into one of four groups. Each group completed four different treatment regimens (placebo-placebo; 80 mg of aspirin-500 mg of niacin; 325 mg of aspirin-500 mg of niacin; and placebo-500 mg of niacin). Subjects received one of each of the four treatment regimens on separate visits that were at least 24 hours apart. Intensity and tolerability of cutaneous reactions were evaluated by an intensity rating scale and a visual analog scale. RESULTS: Results indicate that 325 mg of aspirin is significantly better than 80 mg of aspirin in decreasing intolerability to niacin. Aspirin reduced the incidence of warmth and flushing associated with niacin, but not the itching and tingling. CONCLUSIONS: It appears from this pilot study that preceding niacin with 325 mg of aspirin will decrease the warmth and flushing associated with niacin.

Optimizing drug delivery from metered-dose inhalers.

Metered-dose inhalers (MDIs) are being used with increasing frequency to administer medication used in the treatment of respiratory tract disorders. Inhaled medication is delivered directly to the tracheobronchial tree, allowing for a rapid and predictable onset of action. Studies show that only about ten percent of the dose from an MDI actually reaches the lung. The site of deposition within the lung is influenced by the aerosol characteristics, interpatient variability, and the technique by which the patient uses the inhaler. Spacer devices have been designed to overcome some of the problems encountered with MDIs and may be beneficial in certain groups of patients. The studies reviewed in this article suggest ways to alter the variables affecting inhalation in order to optimize drug delivery so that the patient will obtain the most benefit from the inhaled medication.