Canada Inc Research Articles

Review of systematic reviews on acute procedural pain in children in the hospital setting.

Acute pain is a common experience for hospitalized children. Despite mounting research on treatments for acute procedure-related pain, it remains inadequately treated. To critically appraise all systematic reviews on the effectiveness of acute procedure-related pain management in hospitalized children. Published systematic reviews and meta-analyses on pharmacological and nonpharmacological management of acute procedure-related pain in hospitalized children aged one to 18 years were evaluated. Electronic searches were conducted in the Cochrane Database of Systematic Reviews, Medline, EMBASE, the Cumulative Index to Nursing and Allied Health Literature and PsycINFO. Two reviewers independently selected articles for review and assessed their quality using a validated seven-point quality assessment measure. Any disagreements were resolved by a third reviewer. Of 1469 published articles on interventions for acute pain in hospitalized children, eight systematic reviews met the inclusion criteria and were included in the analysis. However, only five of these reviews were of high quality. Critical appraisal of pharmacological pain interventions indicated that amethocaine was superior to EMLA (AstraZeneca Canada Inc) for reducing needle pain. Distraction and hypnosis were nonpharmacological interventions effective for management of acute procedure-related pain in hospitalized children. There is growing evidence of rigorous evaluations of both pharmacological and nonpharmacological strategies for acute procedure-related pain in children; however, the evidence underlying some commonly used strategies is limited. The present review will enable the creation of a future research plan to facilitate clinical decision making and to develop clinical policy for managing acute procedure-related pain in children.

Oscillometric measurement of the ankle-brachial index

Peripheral arterial disease is a coronary risk equivalent; a low ankle-brachial index (ABI) is indicative of systemic vascular disease, and should place a patient in the high-risk category. Few physicians measure ABI because it is technically challenging and time consuming. Oscillometric blood pressure monitors are readily available and easy to use. The use of a simple method of documenting ABI was assessed and compared with the conventional method. The oscillometric ABI (OABI) was measured for normal volunteers, patients attending a cardiovascular risk clinic (Cardiovascular Risk Factor Reduction Unit [CRFRU] at the University of Saskatchewan, Saskatoon) and patients referred to a vascular laboratory (vasc lab). The latter group had Doppler ABI (DABI) measurements and served to validate OABI. An Omron HEM 711C oscillometric system (Omron Canada Inc) with appropriate cuff size for arm and leg circumference was used. The mean +/- SEM OABI was 1.13+/-0.08 in normal volunteers (n=26), 1.10+/-0.10 in CRFRU patients (n=11, P not significant) and 1.03+/-0.14 in vasc lab patients (n=57, P<0.05 compared with normal volunteers). No difference was found between sexes, and there was no correlation with age. In the vasc lab group, the correlation with DABI was 0.71 (P<0.05). The sensitivity of OABI to detect DABI of less than 0.9 was 0.71, and the specificity was 0.89. OABI was found to be less sensitive at detecting low values in patients with nonpalpable pulses on physical examination. The OABI is feasible and operator-independent, but does not detect low ABI efficiently. If OABI is abnormal, low DABI is likely. The OABI is less likely to detect disease in patients with nonpalpable peripheral pulses. Such patients are better referred directly to a vascular laboratory for DABI testing.

Meeting Report: Research Topics in Gastrointestinal Disease VII

Recent advances in gastrointestinal (GI) diseases are a direct result of the rapid development in fundamental research using cellular and molecular biology approaches. These approaches have helped define normal physiological processes of the GI tract and the pathogenesis of disease mechanisms. The Canadian GI research communities are world leaders in contributing to these efforts in all disciplines relevant to GI disease. This success has been achieved by fostering an excellent cohort of graduate and postgraduate research trainees involved in GI research at institutions across Canada. Many of these trainees are funded by the Canadian Association of Gastroenterology (CAG) in collaboration with the Canadian Institutes of Health Research (CIHR), a number of industry partners and the Crohn’s and Colitis Foundation of Canada. In recognition of the value of the Canadian GI trainees outstanding research contributions, and to promote and encourage the continued efforts of the graduate and postgraduate research trainees in basic and clinical sciences, the CAG, in conjunction with AstraZeneca Canada Inc and the CIHR, held the sixth Symposium on Research Topics in Gastrointestinal Disease, October 13 to 15, 2006 (Figure 1). The goal of this meeting was to provide research trainees with an opportunity to informally present their original research, from diverse disciplines, to their peers and to a selection of faculty from across Canada. In this forum, trainees actively participated in the discussions of papers in an open setting. This year’s program consisted of a series of superb presentations describing cutting-edge research with 38 podium scientific presentations of basic and clinical GI-related research, covering mechanisms of gut inflammation, enteric flora and epithelial barrier functions, hormones that modulate gut responses, epithelial and transport mechanisms, pathogens that initiate inflammatory processes and cancer, and gastric ulceration and healing mechanisms. This year’s keynote lecture was given by Dr John Wallace on “Hydrogen sulphide and inflammation: What’s all the stink about?” The emphasis was on the emerging anti-inflammatory role of hydrogen peroxide and how this important information can have potential commercial benefits in the development of therapeutics in inflammatory disorders.

English

A geochemical study was completed as part of an Environmental Assessment Report for De Beers Canada Inc. Snap Lake diamond mine located in the Canadian Northwest Territories. The deposit will be mined using underground methods and consists of a diamond bearing planar kimberlite dyke dipping at about 15 degrees, hosted in metavolcanic and granite rock. Processing will include grinding of the kimberlite ore and a gravity separation circuit on this ore which will result in processed kimberlite waste including a coarse fraction and a finer fraction which will be used to produce a cemented paste backfill material. The cemented paste composed of processed kimberlite, dilution rock, and cement is thickened to a paste-like consistency and will be used to fill the mine voids. The study discussed in this paper was completed to evaluate potential leachate chemistry of the alkaline cemented paste backfill material slated for use underground. The laboratory test program included solids testing, short-term leach testing, and longer-term kinetic testing on a variety of cemented paste blends and additives. Results show that the pH of the leachate remained alkaline for subaqueous test cells and decreased over time for sub-aerial test cells. Geochemical speciation modeling using PHREEQC that was completed to further evaluate leachate chemistry for site specific conditions indicated probable solubility constraints due to secondary mineral precipitation for parameters calcium, chromium, manganese and nickel.

A phase I/II study of capecitabine (X), irinotecan (I) and oxaliplatin (O) as first-line therapy in patients (pts) with advanced or metastatic colorectal cancer (MCRC)

13540 Background: Triplets of I, O and infusional 5-FU/Leucovorin (LV) are associated with high response rates and long survival in first-line MCRC [Falcone et al. JCO 2002;20:4006–14]. The oral fluoropyrimidine X has proved higher response rates and improved safety vs. 5-FU/LV in MCRC. Methods: This ongoing dose-escalation study aims to establish dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of I and O in combination with X as first-line therapy for MCRC and to assess the efficacy and safety of this XIO combination. Starting doses were: I (180mg/m2 i.v. on day 1), O (85mg/m2 i.v. on day 1), and X (850mg/m2 bid orally on days 2–15). Dose escalations are based on toxicity observed at the previous dose level (DL), until DLT, MTD and RPIID are documented, at which time a phase II component begins. Results: We enrolled 18 pts (13 men, 5 women), median age 61 (range 44–74) at 4 DLs. ECOG PS was 0 or 1 in 17 pts, and 2 in 1 pt. Pts received a median of 7 cycles (range 1–15) of XIO. All pts are evaluable for toxicity and 14 for response. The most common adverse events were: neutropenia (83% all grades (G) with 4 G3, 4 G4), diarrhea (67%, 4 G3, one of which was a DLT). Nausea (78%) and vomiting (56%) were mild and controlled with anti-emetics. Fatigue occurred in 50% pts, with 1 G3. The DLT was febrile neutropenia (3 pts at DLs 1, 3, &amp; 4 respectively). One pt at DL4 developed severe neutropenia and sepsis during cycle 3, had aspiration pneumonia and died in hospital from respiratory and cardiac complications. MTD has not yet been reached. Responses were observed at all DLs: 11 partial responses with 2 still unconfirmed (79%, 95% CI 54–100), and 2 stable disease (14%). Progression-free survival and overall survival have not been reached. Conclusions: XIO is well tolerated and demonstrated significant efficacy as first-line treatment in MCRC. Severe neutropenia was significant but was of short duration and manageable. It is likely to be the main DLT. MTD has not yet been identified but is expected in the next few pts. A phase II study to confirm the efficacy and safety of the XIO combination will follow. Supported by Roche, Sanofi Aventis, and Pfizer Canada Inc. [Table: see text]

Left ventricular function following adjuvant chemotherapy for breast cancer: The NCIC CTG MA5 experience

522 Background: Cardiac toxicity associated with anthracylines and more recently herceptin used in adjuvant breast cancer treatment is well recognized. Little is known about long term cardiac function as measured by left ventricular ejection fraction (LVEF) in patients post therapy. We analyzed the database of a randomized Phase 3 NCIC CTG study to assess changes over time in LVEF. Methods: Between 1989–1993, 710 pre/perimenopausal patients with node positive breast cancer were allocated to receive CEF (cyclophosphamide (C) 75 mg/m2 po d 1–14, epirubicin (E) 60 mg/m2 IV and fluorouracil (F) 500mg/m2 IV d1,d8) or CMF (C 100mg/m2 po d1–14, methotrexate (M) 40mg/m2 and F 600mg/m2 IV d1,8) given every 28 days for 6 cycles. The 10 year relapse-free survival was 52% (CEF) vs 45% (CMF), HR 1.31; stratified log rank, P=.007 (JCO, 2005,23;5166). LVEF was measured on both arms at baseline, months 6, 12, 36, and 60. Results: Compliance was good with measurements available on 100% of women at baseline, and 39% and 40% of patients at 60 months on the CEF and CMF arms respectively. Changes in LVEF from baseline are shown in the table . Conclusion: Changes in cardiac function as measured by a decrease in LVEF are not infrequent in patients after adjuvant therapy, even in the absence of anthracyclines. At 60 months, decreases of &gt;10% were seen in up to 25% of patients receiving epirubicin administered at a cumulative dose of 720mg/m2 and in up to 10% of patients receiving CMF on whom measurements were available. The clinical significance of these findings needs to be assessed. Acknowledgements: This study was supported by funding from the Canadian Cancer Society through the National Cancer Institute of Canada and Pfizer Inc. [Table: see text] [Table: see text]

Questions and answers on immunization

QUESTION: Does regular topical use of tacrolimus or pimecrolimus alter the antibody response to immunization? COMMENT: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that causes significant suffering and has limited treatment options. Because of a perception by physicians and patients that topical tacrolimus (Protopic, Astellas Pharma Canada) and pimecrolimus (Elidel, Novartis Pharmaceuticals Canada Inc) are safer than steroid preparations, abetted by heavy direct-to-consumer advertising, these topical immunomodulators (TIMs) have been increasingly used as first-line therapy in paediatrics. TIMs are indicated for children two years and older with refractory AD, or those who have experienced local or systemic side effects with topical steroids. TIMs act by suppressing T cell and mast cell activation, inhibiting inflammatory cytokine release and downregulating aberrant expression of high-affinity immunoglobulin E receptors on Langerhans cells. In early 2005, public attention was focused on these new medications when the United States Food and Drug Administration posted an advisory warning of a potential cancer risk from the use of TIMs (1,2). This advisory was based on animal studies, case reports in a small number of patients and mechanisms of action of the drugs. Beyond the possible cancer risk, many other questions are now being raised concerning these new medications, including whether TIMs have any effect on the immune response following immunization. Two recent studies have addressed this question directly. The first, by Stiehm et al (3), examined seroconversion after vaccination with the pneumococcal polysaccharide vaccine (Pneumovax 23, Merck Frosst Canada Ltd) in children treated with tacrolimus ointment. Children aged two to 12 years with moderate to severe AD were treated twice daily for six weeks with tacrolimus 0.03%. After the third week of treatment, they were immunized using the 23-valent polysaccharide vaccine, and all subjects developed protective antibody titres to the majority of pneumococcal serotypes examined. This was not a rigorous test of immune function because responses to this vaccine involve only B lymphocytes and in some instances only involve boosting naturally acquired immunity to the common types. The second study, by Papp et al (4), examined the impact of pimecrolimus on the development of protective antibodies following the primary vaccination series. Subjects used pimecrolimus intermittently, twice daily for one to two years, starting at the first sign of a flare and continuing until clearance. Serum concentrations of antibodies against tetanus, diphtheria, measles and rubella were measured at months 18 and 24. The seropositivity rates were comparable with those reported in the general population. Importantly, seropositivity was not significantly affected by the use of pimecrolimus at the time of vaccination. While these data provide some assurance that long-term treatment with pimecrolimus in children does not interfere with antibody production after primary vaccinations, the final word awaits a properly controlled study. In conclusion, treatment of AD with TIMs does not appear to interfere with antibody production following vaccination, based on limited data. However, it is important to stress that TIMs should only be used as a second-line therapy in patients two years of age or older who are unresponsive to or intolerant of conventional steroid therapies. The Upshots column in Paediatrics & Child Health is meant to address practical questions without ready answers in standard references such as the Red Book or the Canadian Immunization Guide. Readers are invited to submit questions to the journal office. A timely response will be provided, whenever possible, from one member of a panel of experts. The most interesting exchanges will be selected for publication. Submitters should identify themselves, but will be given the option of anonymity in the published version. Submitted questions may be edited for clarity and brevity. David Scheifele, MD Associate Editor, Paediatrics & Child Health

Canadian Consensus Conference on Menopause, 2006 Update

To provide guidelines for health care providers on the management of menopause in asymptomatic healthy women as well as in women presenting with vasomotor symptoms, urogenital, sexual, and mood and memory concerns and on specific medical considerations, and cardiovascular and cancer issues. Prescription medications, complementary and alternative medicine (CAM), and lifestyle interventions are presented according to their efficacy in treating menopausal symptoms. MEDLINE and the Cochrane database were searched for articles from March 2001 to April 2005 in English on subjects related to menopause, menopausal symptoms, urogenital and sexual health, mood and memory, hormone therapy, CAM, and on specific medical considerations that affect the decision of which intervention to choose. The quality of evidence is rated using the criteria described in the report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice are ranked according to the method described in this report (see Table 1). The development of this consensus guideline was supported by unrestricted educational grants from Berlex Canada Inc, Lilly Canada, Merck Frosst, Novartis, Novogen, Novo Nordisk, Proctor and Gamble, Schering Canada, and Wyeth Canada.

Gastrointestinal Stromal Tumours: Consensus Statement on Diagnosis and Treatment

In the multidisciplinary management of gastrointestinal stromal tumours (GISTs), there is a need to coordinate the efforts of pathology, radiology, surgery and oncology. Surgery is the mainstay for resectable nonmetastatic GISTs, but virtually all GISTs are associated with a risk of metastasis. Imatinib 400 mg/day with or without surgery is the recommended first-line treatment for recurrent or metastatic GIST; a higher dose may be considered in patients who progress, develop secondary resistance or present with specific genotypic characteristics. Adjuvant or neoadjuvant imatinib is not advised for resectable nonmetastatic GISTs. Neoadjuvant imatinib may be considered when surgery would result in significant morbidity or loss of organ function. Follow-up computed tomography imaging is recommended every three to six months for at least five years. Patients with metastatic disease should be continued on imatinib due to the high risk of recurrence on discontinuation of therapy. Treatment should be continued until there is progression or intolerable adverse effects. If dose escalation with imatinib fails, a clinical trial with novel agents alone or in combination may be considered. The present recommendations were developed at a surgical subcommittee meeting and a subsequent full Advisory Committee meeting held in Toronto, Ontario, in April 2005, under the sponsorship of Novartis Pharmaceuticals Canada Inc.

Message from the CAG President

This article has no abstract.

“Wake Me Up before You Go-Go”. Drug, ‘Wham’, Scope, then Snooze. Can’t We do Better with Conscious Sedation for Endoscopy?

The words of British singer George Michael, in the title of the present editorial, might make some of us think back to our halcyon days when we were young, or at least younger; however, I very much doubt he was highlighting the issues surrounding conscious sedation for endoscopy, although I have not actually asked him about this. Nevertheless, the song title perfectly encapsulates a fairly common situation in endoscopy units where patients are either ‘oversedated’, with a significant recovery period, or do not even feel the ‘sedative’ benefits properly until the procedure is actually completed. I am sure endoscopists are all familiar with the situation in which a patient is somewhat combative during an endoscopic procedure but sleeps like a baby for what seems like ages after the procedure has been completed. Despite undoubted advances in this whole sphere, it is glaringly obvious that there is significant room for improvement in how patients are sedated. Dr Michael F Byrne Gastrointestinal (GI) endoscopy is generally performed under conscious sedation. The most common practice, certainly in North America and much of Europe, is to use intravenous doses of benzodiazepines, usually midazolam, and opiates such as meperidine (Demerol, sanofiaventis Canada Inc) or fentanyl with the level of sedation depending to some degree on the type of procedure and the patient. Diazepam is also used quite commonly, either alone or in conjunction with midazolam. Although we generally think of these agents as ‘safe’, morbidity rates of one in 200 to one in 2000, and occasional mortality, usually due to cardiorespiratory complications, have been reported. To address these concerns, organizations such as the American Society of Anesthesiologists and the American Society for Gastrointestinal Endoscopy devised more formal practice guidelines for conscious sedation that included the use of supplemental oxygen and revised dosing guidelines recommending titration of sedative medications rather than bolus doses. The issue of bolus versus titrated sedation would need to be addressed in its own article to do it justice, but it is my impression that most of my colleagues in units across Canada and the United Kingdom use bolus sedation. Having previously worked in the Duke Medical Center in the United States, I shudder at the thought of returning to nurse-directed titration. I recall many instances in Duke where it could take up to 30 min for the patient to be deemed ‘ready’ for endoscopy, particularly for procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography. Clearly, this would have a huge negative impact on our already suboptimal situation where we are trying to meet an ever increasing demand for endoscopy. It is debatable if titration improves safety or patient satisfaction. Assuming we are stuck with bolus administration, how are we doing with standard sedation using midazolam and fentanyl? My own routine practice is to use 2 mg to 3 mg of midazolam along with 50 μg to 100 μg of fentanyl for colonoscopy, to which I often add 5 mg to 10 mg of diazepam for ERCP. If I do actually sedate patients for upper GI endoscopy, I use 1 mg to 3 mg of midazolam on average. Many of our patients do well with such drug regimens, but we do see a number of patients for whom endoscopy was not a comfortable experience, and we struggle with the amount of time it takes to safely recover the patient before he or she leaves our unit.

Message from the CAG President

Message from the CAG President

Erythropoietin and Hepatitis C Therapy: Useful Adjuvant Therapy but Remember to Treat the Patient and Not Just a Number

For most of the decade, the commercial availability of peginterferon (pegIFN) and ribavirin (RBV) combination therapy for the treatment of chronic hepatitis C virus (HCV) has allowed both patients and health care professionals alike to expect a reasonable likelihood of long-term viral clearance. Both pegIFN and RBV combination products (ie, pegIFN α-2a and RBV, [Pegasys RBV, Hoffman-La Roche Ltd, Canada], and pegIFN α-2b and RBV, [Pegetron, Schering Canada Inc]) are associated with sustained virological response (SVR) probabilities of approximately 40% to 50% for genotype 1 and approaching 80% for genotypes 2 and 3 (1-3). Moreover, the impressive results reported in randomized clinical trials have also been reported in a retrospective analysis of clinical practice (4), going against the common wisdom that results obtained in a ‘real world’ clinical setting cannot match those obtained in the ‘ideal world’ of controlled trials. Despite this great optimism regarding HCV treatment, the cold hard reality is that pegIFN and RBV combination therapy is lengthy, taking approximately 24 to 48 weeks depending on the genotype; has many adverse effects, such that it is an unpleasant experience for many and punishing for some; and is very expensive, with an associated drug acquisition cost of $10,000 to $20,000 for 24 and 48 weeks of therapy, respectively. Although it would appear intuitive for any treatment regimen, that to maximize the likelihood of success one must take as much of the drug as possible, for pegIFN and RBV therapy, given the mentioned problems associated with therapy, the stakes are even higher.

Mitogen-activated protein (MAP) kinase signaling through calcineurin-dependent pathways in cardiac fibroblasts

Calcium/calmodulin-calcineurin dependent signaling has been implicated in cardiac hypertrophy. Downstream targets underlying calcineurin-mediated cardiac actions are unclear, but may involve activation of mitogen-activated protein kinases (MAP) kinases. In the present study we questioned whether calcineurin regulates ERK1/2, p38MAPK and JNK, important signaling molecules contributing to cardiac growth, apoptosis, fibrosis and inflammation. Rat cardiac fibroblasts were studied. Cells were treated with ionomycin (10-5 mol/L) or Ang II (10-8- 10-6 mol/L) in the absence and presence of FKC506 (10-8–10-6 mol/L) or cyclosporine A (10-8-10-5 mol/L) calcineurin inhibitors. Ionomycin, a Ca2+ ionophore, which increased intracellular free Ca2+ concentration as measured by fura 2 fluorescence, and Ang II significantly increased phosphorylation of ERK1/2, p38MAPK and JNK by 8–10 fold (p<0.01 vs controls). FKC506 pretreatment completely abolished ionomycin-induced effects. Cyclosporine A also reduced ionomycin actions, but responses were less than those produced by FK506. Ang II-mediated actions were not influenced by calcineurin inhibitors. Total MAPK protein content was unaltered by FKC506 and cyclosporine A. These results suggest that ERK1/2, p38MAPK and JNK are potently activated by Ca2+- and Ang II-dependent signaling pathways. Whereas MAP kinase regulation by Ca2+/calmodulin is calcineurin-dependent, Ang II regulation of cardiac fibroblast MAP kinase is calcineurin-independent. Our data indicate differential activation of MAP kinases in cardiac fibroblasts. Supported by Fujisawa Canada Inc.

18 STRATEGIES TO IMPROVE FERTILITY WITH COSYNCH-CIDR PROTOCOLS IN BEEF CATTLE

Two experiments were designed to evaluate strategies to improve fertility with Cosynch-CIDR protocols in cattle. The first experiment investigated the effect of low levels of progesterone prior to a Cosynch-CIDR protocol. On Day 0, lactating beef cows (n = 34) and heifers (n = 37) were placed in two groups to receive 500 μg cloprostenol (PGF; Estrumate, Schering-Plough Animal Health, Pointe-Claire, Quebec, Canada) or a twice-used CIDR (Bioniche Animal Health, Belleville, Ontario, Canada) for 5 days (Pretreatment) or no treatment (Control). On Day 5, used CIDRs were removed and all cattle received a new CIDR (Pfizer Animal Health, Montreal, Quebec, Canada) and 100 μg GnRH (Cystorelin, Merial Canada Inc, Victoriaville, Quebec, Canada). On Day 12, CIDR were removed and PGF was given. A second GnRH was given concurrent with timed AI (TAI) on Day 14 (54–56 h after PGF). Cattle were examined by transrectal ultrasonography for CL and follicle development, and for confirmation of pregnancy (Days 42 to 49). Diameter of the dominant follicle on Day 5 was larger and more variable in cows than in heifers (15.5 ± 5.6 vs. 11.4 ± 3.5 mm, respectively; means, P &lt; 0.001; variance, P &lt; 0.003), and tended to be larger in the Pretreatment group (14.3 ± 4.9 vs. 12.6 ± 5.2 mm; P = 0.13). More Pretreated (60.0%) than Control (36.1%) cattle (P &lt; 0.005), and more cows (64.7%) than heifers (32.4%; P &lt; 0.03) ovulated following the first GnRH. At the time of TAI, 5 (13.5%) heifers had already ovulated (P &lt; 0.03). Diameter of the preovulatory follicle was affected by parity (P &lt; 0.001), but not Pretreatment (P = 0.4), and tended to be larger in heifers that became pregnant (P = 0.13). Pregnancy rate was not affected by parity (P = 0.71), or pretreatment (P = 0.34); pretreatment tended to increase pregnancy rate in heifers (63.2 vs. 38.9%; P = 0.19). The second experiment evaluated the use of eCG in a Cosynch-CIDR protocol in beef heifers. Beef heifers (n = 127) were fed 0.5 mg/head/day of MGA (Pfizer Animal Health) for 15 d; 12 d after the last feeding (designated as Day 0) heifers received a CIDR and 100 μg GnRH. On Day 7, CIDR were removed, and heifers received PGF, and were randomly placed in 2 groups to receive 300 IU of eCG (Pregnacol; Bioniche Animal Health) or no treatment (Control). On Day 9 (54–56 h after PGF), all heifers received 100 μg GnRH, concurrent with TAI. Ultrasonographic examinations were done as in the first experiment. Overall, 79.5% of the heifers had a CL, and 9.4% had a luteinized follicle on Day 0. Seventy-eight heifers (61.4%) ovulated following the first GnRH, and those that ovulated had a less variable preovulatory follicle size than those that did not (13.7 ± 1.7 vs. 13.8 ± 2.3 mm; means, P = 0.76; variance, P &lt; 0.01). However, there was no difference in preovulatory follicle size (P = 0.63), or pregnancy rate (49.2 vs. 53.1%; P = 0.7) for eCG-treated vs. Control heifers. In summary, pretreatment with a twice-used CIDR plus PGF increased the proportion of cattle that ovulated to the first GnRH, but not preovulatory follicle size or fertility in cows; fertility tended to be improved in heifers. Treatment with eCG did not increase preovulatory follicle size or fertility in heifers subjected to an Cosynch-CIDR protocol.

Monsanto v Schmeiser: A Landmark Decision concerning Farmer Liability and Transgenic Contamination: Monsanto Canada Inc v Schmeiser

Monsanto v Schmeiser: A Landmark Decision concerning Farmer Liability and Transgenic Contamination: Monsanto Canada Inc v Schmeiser

P.1.096 Correlation of changes in electrical brain activity with changes in Hamilton depression rating scale after daily application of hypericum extract for six weeks in depressive patients

The two most common albuterol preparations used for nebulization are: (1) Ventolin (albuterol) respirator solution (Glaxo Canada Inc; Montreal, Canada) of which 2.5 mg (0.5 mL) is diluted with 2 mL of normal saline solution, and (2) the preservative-free, prediluted Ventolin (albuterol) Nebules PF (Glaxo) (2.5 mg/2.5 mL). The two preparations were compared using both a Hudson 1720 “T” up-draft Neb-U-Mist jet nebulizer and a Hudson 1730 “T” up-draft Neb-U-Mist II jet nebulizer (Hudson; Temecula, Calif), which were driven by a compressor (Pulmo-Aide; Devilbiss; Somerset, Pa) and by dry compressed air at 6 and 8 L/min. Particle size distribution was measured with a particle sizer (Malvern 2600; Malvern Instruments; Malvern, UK) and drug output for the nebulizer was calculated from the differences in predrug and postdrug volume and concentration. Drug availability was defined as the amount of drug carried in particles less than 5 µm in diameter. Drug availability was greater with the albuterol respirator solution, due to the surface activity of the preservative benzalkonium chloride, for both nebulizers but particularly for the 1720. Differences in drug availability between nebulizers exceeded fourfold depending on the preparation, the nebulizer, and the nebulizing flow. These differences could not have been predicted from the manufacturer's specifications. The results suggest that prediction of drug availability must be based on measurements with the specific preparation and the specific nebulizer used.

Update from Canadian Respirology Program Directors

Submitted by Elizabeth Tullis MD FRCPC Associate Professor of Medicine, Respirology Program Director, University of Toronto, Toronto, Ontario The Canadian Organization of Pulmonary Program Directors (COPPD) had their first meeting in Montreal on November 7, 2003, which was sponsored by an unrestricted educational grant from AstraZeneca Canada Inc. This meeting was held in conjunction with the Royal College of Physicians and Surgeons (RCPS) Respirology Subspecialty Committee meeting held on November 6, 2003, and with the first Canadian Division Directors meeting held on November 8, 2003.

Internet gambling, credit cards and money laundering

Contrasts the approaches to offshore Internet gambling taken by the UK and the USA: the Budd Committee recommended that it be permissible under license in the former, but it is arguably illegal for an offshore operator to accept wagers from the USA ‐ and most gaming sites are well outside the USA. Discusses a number of US legal cases, many of them involving the Racketeer Influenced and Corrupt Organizations Act (RICO): State of New Jersey v RoyalclubCasino.com et al, In Re Gaming Lottery Securities Litigation, Providian Bank v Haines, Jubilirer v MasterCard International, Reves v Ernst and Young, Marino v American Express, Buchal v 3748472 Canada Inc, US v Cohen, In Re MasterCard, US v Truesdale, US v Dennis and Joseph Atiyeh, United States v $734,578.82 in United States Currency. Suggests that the Statute of Anne might be used to minimise Internet gambling by Americans, but concludes that it is doubtful whether Internet gambling can be prohibited and that a licensing system may be practicable.

Book review: The World of Psychology, 3rd Canadian Edition.

SAMUEL E. WOOD, ELLEN R. GREEN WOOD, EILEEN WOOD, and SERGE DESMARAIS The World of Psychology, 3rd Canadian Edition Toronto, ON: Pearson Education Canada Inc, 2002, 592 pages (ISBN 0-205-36456-X, $67.95, Softcover) Reviewed by GIRA BHATT The task of teaching an introductory course in psychology can be quite challenging. The discipline has been growing rapidly and there is a continual influx of new research findings that need to be sifted through, summarized, organized, and incorporated into the course while making it palatable and interesting to the eager minds of the first year of psychology. The challenge is equally daunting for the writers of textbooks who must not only keep pace with the latest developments, but also ensure that the content as well as the style meets the pedagogical demands in the competitive world of textbook publication. Keeping pace with the latest research trends and media technology, writers and publishers have met these challenges quite well. Today's introductory psychology textbooks are multicoloured, filled with colour-coded boxes, tables, diagrams, pictures, photographs, quotations, cartoons, and more (Bhatt & Chan, 1996). Also, almost all introductory textbooks that arrive in the instructors' offices today come as a package loaded with instructors' resources, hundreds of colour transparencies, test-banks, video-tapes, video-discs, CDs, and even the on-line versions of the course with simulated exercises, quizzes, etc. These are now standard features of most introductory psychology textbooks. In fact, that introductory textbooks all look almost alike has made the task of textbook selection quite arduous. Canadian instructors face an additional challenge. A large majority of these textbooks are published in the U.S., written by U.S. authors, and aimed for use of U.S. students. As such, the focus of the textbook content has remained on the U.S. context. The examples illustrating core concepts are replete with American themes such as American demographics, American presidents, American TV shows, American news stories, American baseball, and so on. Canadian do not necessarily relate to these contents and instructors often have to search for Canadian equivalents. It is, therefore, heartening to note an emerging trend of introductory textbooks being published as Canadian. The main issue, however, is what makes an introductory textbook Canadian? Is there any pedagogical value in Canadianizing an introductory psychology textbook? On the surface, it may appear that differences between the U.S. and Canada are only geographical. Yet, if one searches for unique features of life in Canada, one is likely to find plenty. Our political system is different from that of the U.S.. Our multicultural mosaic ideal stands in contrast to the melting pot ideal of the U.S. We have strict gun controls. We have a universal health care system. We do not have a large black population. We tend to be fanatic about ice hockey, and so on. In fact, that we are not like the Americans is a salient feature of our identity as Canadians (Tonks & Bhatt, 1991). Moreover, the differences between life in the U.S. and life in Canada do have significant implications for our academic programs (Bowman, 2000). Wood, Wood, Wood, and Desmarais' The World of Psychology: Third Canadian Edition acknowledges at the outset that students learn best when materials are relevant to their lives (p. xxi). Consequently, they have integrated Canadian content throughout the text, including Canadian demographics, Canadian illustrations, Canadian historical events, and media references. Six of the 14 chapters have opening vignettes that are interesting and relevant to life in Canada. For example, one chapter opens with a story about the youth gang of Spadina girls in Toronto and the Reena Virk tragedy in Victoria, which highlight the violence among young women in Canada. Another chapter opens with an interesting news story about conjoined twins from Pakistan who were flown to Toronto's Hospital for the Sick Children to undergo a surgery to separate their heads. …