Introduction
The publication of the landmark Heart Outcomes Prevention Evaluation (HOPE) Study¹ in the New England Journal of Medicine in January 2000 was greeted by a great deal of excitement in the medical community. In essence, the trial confirmed beyond a doubt the cardiac and renal protective benefit of ACE inhibition and extended the patient base in whom ACE inhibition has been proven effective. Our understanding of the cardioprotective nature of ACE inhibitors has been built over the years by the various mega-studies that have been conducted, dating back to the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS),² published in 1987, which showed a 31% survival advantage for ACE inhibition in New York Heart Association (NYHA) class IV heart failure patients. Thirteen years and more than a dozen large trials later, the HOPE study has confirmed that patients need not be so sick--indeed, need only be considered at risk for cardiovascular events--for ACE inhibition to show similar benefits. Looking down the list, from CONSENSUS to HOPE and several landmark trials in between, one would be hard pressed to find a class of agents with a wealth of compelling evidence comparable to that accumulated for ACE inhibitors.

Main Results and Significance
The HOPE study investigators found that 17.

Is it Ethical to Use Foetal Tissue for the Treatment of PD?

David Kaplan, MSc(HA)
Joint Centre for Bioethics
Faculty of Medicine,
University of Toronto

Surgical transplantation of foetal brain cells has been reported to substantially improve the symptoms associated with Parkinson's Disease. Parkinson's disease, which is characterized by tremors, muscular rigidity, and akinesia, is believed to result from the deterioration of the brain's dopamine producing cells in the substantia nigra (the neural centre for the initiation and control of movement). This disease afflicts 70,000 Canadians, and unfortunately, approximately ten percent of these patients are refractory to conventional medical therapy. Clearly, new methods to control the disease would be of substantial benefit to these patients. In 1995, the Canadian government introduced legislation that would have made it difficult, if not illegal, to conduct research into foetal tissue transplant. Although this Bill died on the parliamentary order desk, there remains the prospect of reintroducing such legislation. The purpose of this article is to examine the murky ethical waters that surround the topic of research and therapy involving foetal tissue. However, I will not attempt to validate the merits of this therapy in this brief analysis.

Procurement
Obviously, a source of foetal tissue is required, in order to perform foetal tissue transplantation surgery. There are three potential sources for this tissue.

In 1869, french neurologist Jean-Martin Charcot first described a rapidly progressive, fatal neuromuscular disease. This disease, amyotrophic lateral sclerosis, or Lou-Gehrig's disease, is a neurodegenerative disorder that affects the patient's motor neurons; typically the patient is paralyzed or deceased within 2 to 5 years of the initial diagnosis. Currently, approximately 3000 Canadians suffer from this tragic disease.

Andrew Eisen MD, FRCPC
Professor and Head, Division of
Neurology, University of British Columbia,
Head of the Neuromuscular Diseases Unit,
Vancouver General Hospital

Amyotrophic lateral sclerosis (ALS) is a prototypic neurodegeneration of the aging nervous system. It has a worldwide incidence of about 2 per 100,000 members of the population and a prevalence of 4&endash;7 per 100,000. As is true of both Parkinson's and Alzheimer's disease, the incidence of ALS is increasing proportional to the increasing longevity of the population. Information regarding the specific incidence of ALS in the elderly (aged 75 years and older) is sparse. The apparent decrease in incidence of this disease in patients older than 70 years reflects mortality from competing diseases in later life.

The etiopathogenesis of ALS is complex and multi-factorial.

Alejandro Floh, BSc
Medical student,
University of Toronto

Co-authored by:
D'Arcy L. Little, MD, CCFP
Director of Medical Education and Research
York Community Services, Toronto, ON

Introduction
Family physicians are frequently faced with patients who complain of the swelling of one or both of their legs. Although many cases of leg swelling are benign, a systematic approach is necessary in order to avoid overlooking a potentially serious condition.

The principle cause of leg swelling is edema.² Edema is a general term that refers to a "clinically apparent increase in interstitial volume"¹, which arises from capillary filtration that exceeds lymphatic drainage.

History
A comprehensive history is the first step in making a diagnosis of leg swelling. Initially, leg swelling should be classified into two broad categories: unilateral versus bilateral, and acute versus subacute or chronic. In general, this classification should allow one to differentiate between local diseases, which are usually unilateral, and manifestations of systemic conditions, that present as unilateral or bilateral swelling. Major local conditions include deep vein thrombosis (DVT), superficial thrombophlebitis, and cellulitis. Systemic illnesses such as congestive heart failure (CHF), cirrhosis, nephrotic syndrome, and malnutrition usually present with bilateral swelling of the lower extremities.

How to Deliver a Riveting Lecture

As I write these lines, I am sitting through a long, exceedingly dry, and from my own perspective, mostly irrelevant, medical lecture. If this were a rare event, or one that only occurred when I was in the audience, there would be no reason to continue with this piece. In fact, just as I began to pen the end of the previous sentence, the chin belonging to the person seated next to me dropped precipitously to his chest.

There is much evidence (albeit anecdotal) to suggest that this process, oft repeated around the world, is one of the greatest wastes of time known to professional people.

One must first consider the origin and history of "the lecture", to fully comprehend how such a profligate dissipation of professional person-hours has been allowed. Before Herr Guthenberg's timely invention, books were both exceedingly rare and restrictively expensive; as a result, they were not available to the majority of the populace, which in any case, was mostly illiterate.

In medieval universities, the art of teaching involved a professor reading aloud to his students from the one available book. (Thus the word lecture: through Middle English, via Middle French, originating from Latin: lectura, from lectus [past participle of legere: to gather, select, read.])

Books, and the knowledge that lies therein, have always represented power.

Sharon Yardley, RN Clinical
Coordinator, Vancouver Hospital
Movement Disorders Clinic

Co-author
Susan Calne, RN
Coordinator Neurodegenerative
Disorders Centre

Introduction
I work at the Neurodegenerative Disorder Centre at the University of British Columbia, where we currently care for more than 1,500 patients with Parkinson's disease (PD). I work with four neurologists, all of whom have subspecialty training in PD, and on a part-time basis I also have the help of one other nurse. My role as the clinic co-ordinator, is to provide counselling and education to new patients, and as their disease progresses, to continue counselling these patients on an outpatient basis. By providing the patients with knowledge and support, we seek to optimize their quality of life and their independence.¹

The clinical co-ordinator focuses primarily on the patients, and provides them with information about PD, the emotional and employment issues that may arise during the course of the illness, and changes that will occur in their lifestyle. Another important function is to provide the patients with education about pharmaceutical treatment and monitoring services, and to support them as they begin antiparkinson therapy, documenting changes in their symptoms and any problems that occur between visits.

Drugs, Toxins and Pugilism May All Lead to PD-Like Symptoms

D'Arcy L. Little, MD, CCFP
Director of Medical Education
York Community Services,
Toronto, ON

Introduction
Diagnosing a patient with Parkinson's disease might, at first, seem to be straightforward. In some cases, a medical student can make the diagnosis from across a room. However, fully one quarter of the diagnoses of idiopathic Parkinson's, which were made clinically by specialists, were found upon pathological examination to be some other disease.^1,2,3 This figure is even higher in situations where the diagnosis was made in the early stages of the disease, by a non-specialist.³ Given that the list of conditions in the differential diagnosis of Parkinson's is vast, and the diagnosis is essentially a clinical one made by the process of elimination or exclusion, the clinician needs a solid approach when considering a diagnosis of this illness. The purpose of this review is to itemize an approach to the exclusion of cases of secondary parkinsonism, in the diagnosis of idiopathic Parkinson's disease (See Figure 1: Approach to Diagnosis of Parkinsonism). Table 1 lists clues that suggest a diagnosis of secondary parkinsonism.

It is well known that many elderly individuals have difficulty sleeping, and it is also known that aging is associated with a decrease in growth hormone (GH) levels. Changes in sleep patterns drastically affect endocrine function, especially pituitary-dependent hormonal release, which may impact on nighttime levels of GH. An interesting question then, is whether the age-related decrease in the quality of sleep is responsible for the age-related decline in GH hormone secretion or, alternatively, whether the reverse is true and the age-related decline in GH secretion may be responsible for the age-related changes in sleep patterns. A recent study published in the Journal of American Medical Association has taken a step towards determining this relationship, by closely examining the correlation between various stages of sleep and levels of GH, in healthy men between 16 and 83 years of age. The association between the two is striking. Not only does it raise the possibility of using GH supplementation to conquer yet another marker of biological aging--reduced sleep--but it also presents sleep enhancement as a potential way of increasing GH levels.

Previous studies have shown that aging is associated with increases in the number and duration of awakenings during the night and decreases in the amount of slow-wave (SW) sleep. There is also a decrease in the amount of rapid eye movement sleep (REM) but this change is moderate by comparison. This earlier data was based on a comparison of two age groups young and aged persons.

Nadège Chéry, PhD
Medical Writer/Consultant,
Snell Medical Communication Inc.
Montreal, Qc

The prescription of medications is among the most frequent and the most reliable forms of therapeutic strategy that physicians use for the treatment of patients with a variety of medical disorders.¹ Unfortunately, many of these medications also produce side effects, especially in the geriatric population,¹ some of which may be mild and relatively tolerable by most patients, and others, such as dyskinetic reactions, which are considered harmful.^2,10 Drug-induced movement disorders represent an important iatrogenic condition that is occasionally encountered in clinical practice.² These potentially disabling movement disorders are involuntary, they appear to be idiosyncratic extensions of the expected action of the drug and they are known to particularly affect the elderly patient.^2-6 Among the devastating consequences of these disorders are involuntary movements, which may contribute to falls and fractures in the elderly, and social isolation, which can result from the limited mobility of an elderly individual.^4,7

Nonetheless, movement disorders are often reversible; the withdrawal of the offending drug(s) usually leads to the alleviation of symptoms.³ Unfortunately, in some cases, discontinuing the offending drug may not be feasible.

An Interview with Dr. Caleb Finch

Kimby N. Barton, MSc
Associate Editor,
Geriatrics & Aging

This month we are pleased to present, as part of our Biology of Aging series, an interview with Dr. Caleb Finch, a world-renowned gerontologist. Dr. Finch has received most of the major awards in biogerontology, and since 1984, has directed the US National Institute of Aging funded, Alzheimer Disease Research Center. Probably one of Dr. Finch's most significant discoveries was that the brain makes messenger RNAs (mRNAs) for several inflammatory mediators, known as complement factors, that were previously believed to be absent from the brain. In addition, he disproved a longstanding belief that the activity of mRNAs globally decreases with increasing age.

Dr. Finch's current research is focused on the molecular and cellular mechanisms of aging in the brain, and the selectivity of neurodegeneration. His research team is analyzing the transcriptional control, in the brain, of complement factors and other mRNAs that are known to change during aging and with neurodegenerative disease. I was afforded the opportunity to ask Dr. Finch some questions regarding his recent research and major developments in the field of aging.