Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients.

Tamoxifen has been a mainstay of adjuvant therapy for breast cancer for many years. We sought to determine if genetic variability in the tamoxifen metabolic pathway influenced overall survival in breast cancer patients treated with tamoxifen. We examined functional polymorphisms in CYP2D6, the P450 catalyzing the formation of active tamoxifen metabolites, and UGT2B15, a Phase II enzyme facilitating the elimination of active metabolite in a retrospective study of breast cancer patients.

Concanavalin A binding to HIV envelope protein is less sensitive to mutations in glycosylation sites than monoclonal antibody 2G12.

Many mannose-binding proteins inhibit divergent strains of human immunodeficiency virus type 1 (HIV-1) in in vitro models of viral infectivity, suggesting that targeting mannose residues in vaccine applications might offset the strain restriction typically observed in antibody responses to HIV vaccine preparations. Concanavalin A (ConA) behaves like neutralizing antibodies that do not interfere with CD4 binding of gp120 but rather with later events in virus entry. The design of mannose-based vaccines, therefore, depends on understanding the mode of binding of ConA to the envelope protein in comparison with other mannose-binding proteins.

Fish hook injury to the eyelid - an unusual case.

Fishing is recreational activity enjoyed by millions of people worldwide. Although uncommon in developing countries it is a popular pastime in the Western world. and, given this popularity, a number of associated personal injuries are probably inevitable.

Targeting carbohydrate antigens in HIV vaccine development.

Peptide mimotopes provide a strategy to augment human immunodeficiency virus 1 (HIV-1) specific carbohydrate reactive immune responses. Their antigenic and immunological properties will depend on the optimization of motif clustering and multimerization. We observe that structural variants of the same mimetic motif, linear versus cyclic, can be used to tune the properties of the antibodies elicited.

Symptoms of narcolepsy in children misinterpreted as epilepsy.

Differentiating an epileptic seizure from some other paroxysmal event is a common challenge in clinical practice. Many paroxysmal events mimic epileptic seizures and misdiagnosis can have disastrous consequences. Incorrectly identifying an event as an epileptic seizure can lead to unnecessary investigations and instigation of inappropriate treatment regimes.

Electro-clinical phenotypes of chromosome disorders associated with epilepsy in the absence of dysmorphism.

Chromosome imbalances are associated with epilepsy but electro-clinical phenotypes are lacking for all but the best-known syndromes. Scanty information is contained in older case reports published in genetics journals that describe children with severe patterns of malformation and dysmorphism. From a larger series of children with chromosome abnormalities and epilepsy, we identified 10 patients with associated dysmorphism without malformation.

Resistance to antibiotics: administrative response to the challenge.

The authors discuss antibiotic resistance within a conceptual framework that illustrates the dynamic relationships among antibiotic, patient, and population factors. The complexity of these interactions makes it unlikely that any single intervention or approach will adequately address the problem of increasing rates of antibiotic resistance. A case study focused on Streptococcus pneumoniae in the context of community-acquired pneumonia provides a detailed examination of the manner in which antibiotic use, expenditures, and microbial resistance are affected by an administrative reimbursement restriction implemented by a single government payer.

Nasal/buccal midazolam use in the community.

A telephone survey was carried out to evaluate the effectiveness and convenience of nasal/buccal midazolam in terminating prolonged seizures in the community. A total of 33/40 (83%) families who had used it found it effective and easy to use; 20/24 (83%) preferred using midazolam to rectal diazepam.

Hospitals and academic health sciences centres: leaders or followers in health globalization?

The overall impact of globalization on health outcomes is contentious, but there is no doubt that knowledge transfer and the extension of specific health interventions to developing countries promise extraordinary benefits. It has been suggested that improved information/communications technology and the creation of distributed hospital systems leading a virtual healthcare web will permit realization of the promise of globalization. It is argued in this commentary that such evolution will require a new model of shared governance in the healthcare system.

Rapid increase in statins newly dispensed to Ontario seniors between 1994 and 2000.

Background: The Ontario government spent approximately 10% (CDN $148 million) of the provincial medication budget on statins in 1998. This number can be expected to grow in light of new guidelines from the United States recommending that three times as many patients should be receiving antihyperlipidemic therapy. There is scant population-based information on the age and sex distributions of patients receiving these medications.

Collaborative practice: a strategy to improve the relevance of health services research.

Health services research has emerged as a tool for decision makers to make services more effective and efficient. While its value as a basis for decision making is well established, the incorporation of such evidence into decision making remains inconsistent. To this end, strengthening collaborative relationships between researchers and healthcare decision makers has been identified as a significant strategy for putting research evidence into practice.

Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk.

A case-control study of colorectal cancer, consisting of 157 cases and 380 controls matched by sex, ethnicity, decade of age and county of residence was performed to explore the associations between environmental exposure, metabolic polymorphisms and cancer risk. Participants were required to provide a blood sample, undergo caffeine phenotyping and complete an in-person interview that evaluated meat consumption, cooking methods and degree of doneness. A color atlas of foods cooked to different degrees of doneness was used to estimate food preparation techniques and food models were used to estimate serving portion sizes.

FRCSEd (Oral and Maxillofacial Surgery): a milestone in the history of Oral and Maxillofacial Surgery in the United Kingdom.

The British Association of Oral and Maxillofacial Surgeons (BAOMS) and the Royal College of Surgeons of Edinburgh (RCSEd) have had leading roles in organisation, assessment and improvement of surgical training in the United Kingdom. This was particularly well illustrated by the establishment of the fellowship examination in Oral and Maxillofacial Surgery (FRCSEd, OMFS).

Experimental keloid scar models: a review of methodological issues.

Background: Keloid scars are benign fibrous proliferations in the dermis that arise after dermal trauma. The scars are raised in appearance and extend beyond the boundaries of the original wound. Scarring in predisposed individuals is out of proportion to the severity of the inciting wound.

Pathophysiological effects of nicotine on the pancreas: an update.

Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic diseases. It is well recognized that nicotine, a major component in cigarette smoke, is an addictive agent and, therefore, reinforces smoking behavior. The current review update focuses on the genetics of nicotine dependence and its role on the development of pancreatic diseases.

Expression of fas ligand in metastatic prostatic carcinoma: suggestive of possible clonal expansion of subpopulation with metastatic potential.

Fas ligand (FasL) is a type II transmembrane tumor necrosis factor family protein, known to trigger apoptosis in cells that bear the FasL receptor, Fas. The authors found that normal prostate, benign hyperplasia, and most prostatic carcinoma cells at the primary site did not express FasL, whereas metastatic prostatic carcinoma cells in lymph nodes and bone marrow displayed almost uniform, immunohistochemically detectable, FasL expression. However, small foci of FasL-positive prostatic carcinoma cells amid a vast majority of FasL-negative tumor cells were noted at the primary sites in patients with distant metastases.

The Optimal Drug Therapy National Symposium 2001: a call for action.

There is widespread concern internationally and within Canada about the rapid escalation in pharmaceutical costs. Although there is reason to believe that the quality of prescribing has improved in recent years, with heightened emphasis on evidence-based therapeutic decision-making, there is enormous pressure to prescribe in almost every clinical situation. Busy clinicians need improved tools to aid therapeutic decision-making.

The role of human glutathione S-transferases (hGSTs) in the detoxification of the food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a polymorphism in hGSTA1 on colorectal cancer risk.

Food-derived heterocyclic amines (HCAs), particularly 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are implicated in the etiology of human colorectal cancer (CRC) via a process of N-oxidation followed by O-acetylation or O-sulfation to form electrophilic metabolites that react with DNA. Glutathione S-transferases (GSTs) detoxify activated carcinogen metabolites by catalysis of their reaction with GSH. However, among HCAs, only N-acetoxy-PhIP has been shown to be a substrate for the GSTs.

Genetic deletions of glutathione-S-transferase as a risk factor in squamous cell carcinoma of the larynx: a preliminary report.

Purpose: To test whether genetic deletions of glutathione-S-transferase (GST) are associated with squamous cell carcinoma (SCC) of the larynx. GST are a group of detoxifying enzymes that may help reduce the risk of developing cancer in response to environmental carcinogens. Polycyclic aromatic hydrocarbons, found in high concentration in cigarette smoke, are known carcinogens especially for SCC of the larynx.