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Response to Therapy in Acute Myeloblastic Leukemia Dependent on Genetic Make-up of Leukemic Cells

Response to Therapy in Acute Myeloblastic Leukemia Dependent on Genetic Make-up of Leukemic Cells

Teaser: 

M.D. Minden, M.D., Ph.D., FRCPC
Princess Margaret Hospital
University Health Network
Toronto, ON

Introduction
Leukemias are malignancies of the blood and bone marrow and are classified as either acute or chronic malignancies of the myeloid--red blood cell, granulocyte, platelet lineage--or lymphoid--T or B lymphocyte. In this article we will focus on acute myeloblastic leukemias (AML) and recent advances in their classification and therapy.

In the United States, approximately 10,100 cases of AML are diagnosed each year and the yearly mortality rate from this disease is approximately 6,900 individuals. The incidence of AML is low in children (<1/100,000) and increases with age, such that by the time a person reaches the age of 80 the incidence is approximately 15/100,000 (Figure 1).1 Over 60% of patients are 55 years of age or older, making this a significant problem in the aging population.

AML develops as the result of genetic changes in hematopoietic stem cells of the bone marrow.2 These changes block the ability of the cell to undergo normal differentiation resulting in a blast-like morphology. In some cases, the patient may have large numbers of circulating leukemic blast cells compromising blood flow to vital organs.

Radiation Therapy for the Treatment of Esophageal and Gastric Cancers in the Elderly

Radiation Therapy for the Treatment of Esophageal and Gastric Cancers in the Elderly

Teaser: 

Jolie Ringash, MD, MSc
Department of Radiation Oncology,
Princess Margaret Hospital
University Health Network,
Toronto, ON

Background
Esophageal and gastric carcinomas are primarily diseases of older persons. Of 498 new cases of esophageal cancer in Ontario in 1997, 237 (48%) occurred in individuals aged 65 to 79, and 101 (20%) in those over the age of 80. The corresponding numbers for gastric cancer are (of a total of 1,032 cases) 492 (48%) for those aged 65 to 79, and 200 (19%) for those over 80.1 For all age groups, gastric cancer is decreasing in incidence, with only 2, 800 cases in Canada in the year 2000. In contrast, the incidence of esophageal cancers is gradually increasing (1,350 cases in 2000).2,3 Adenocarcinoma, primarily of the distal esophagus, has replaced squamous cell carcinoma as the most frequent histology. Tumours of the gastroesophageal junction pose a particular challenge, since management may differ depending on whether the tumour is felt to originate in esophagus or stomach.

Canadian oncologists frequently face difficult treatment decisions in the elderly. Unfortunately, since older patients are usually excluded from clinical trials, evidence for their tolerance of, and response to, therapeutic radiation is limited. Existing reports are limited to retrospective reviews and subgroup analyses, many of which originate in Japan.

Cancer and Aging: Two Sides of the RecQ-Like Helicase Coin

Cancer and Aging: Two Sides of the RecQ-Like Helicase Coin

Teaser: 

Haim Cohen, Ph.D
Department of Pathology,
Harvard Medical School,
Boston, MA

The incidence of cancer increases as we age: during the last decade of life, the risk of developing cancer is a startling 50% for men and 33% for women.1 What is the underlying link between aging and cancer? This link may be found by investigating diseases that are associated with both a high frequency of cancer and premature signs of aging. Such diseases, known collectively as RecQ syndromes, are caused by mutations in genes encoding RecQ-like proteins.2 The RecQ family of proteins has a high degree of homology to the helicase domain of the RecQ helicase of E. coli. The helicase region is required for all RecQ helicases to unwind duplex DNA from 3' to 5' direction in vitro; however, the in vivo function of the eukaryotic RecQ is unknown.

At least three inherited human diseases are caused by mutations in RecQ-like genes: Werner syndrome (WS), Bloom syndrome (BS), and Rothmund-Thomson syndrome (RTS).3 These diseases share two main features: premature aging and a high level of genomic instability that manifests itself as a high incidence of cancer.

The hallmark of Bloom syndrome is an increased level of sister chromatid exchange, and patients present with sun-sensitive skin pigmentation and a predisposition to certain malignancies.

Multiple Myeloma: The Debilitating Disease that ‘Punches Out’ the Elderly

Multiple Myeloma: The Debilitating Disease that ‘Punches Out’ the Elderly

Teaser: 

Dr. Christine I. Chen, MD, FRCPC
Princess Margaret Hospital,
University Health Network,
Toronto, ON

Introduction
Multiple myeloma arises from a malignancy of plasma cells in the bone marrow which typically produce an immunoglobulin, also referred to as a monoclonal protein (M-protein), that is detectable in the patient's blood and/or urine. Myeloma is not a common disease (incidence of 1400/year in Canada), typically affecting older individuals (median age 65 years). It is more common in blacks and slightly more prevalent in males. Since myeloma is a relatively slow-growing malignancy, many patients will have the disease for months or even years before a diagnosis is made and may continue to follow an indolent course. The pathogenesis of the disease is poorly understood.

Clinical Features
Characteristic clinical features of multiple myeloma are anemia, renal failure, bony lesions with pathologic fractures and associated pain, hypercalcemia, and recurrent infections (See Table 1). Many patients, however, will present with asymptomatic anemia or a monoclonal gammopathy, which is usually discovered during incidental lab testing.

Elderly Patients Excluded from Clinical Trials

Elderly Patients Excluded from Clinical Trials

Teaser: 

Tawfic Nessim Abu-Zahra, BSc, MSc

Elderly people (i.e. those over 65 years of age) tend to be excluded from clinical research trials in areas such as cancer and heart disease.1-4 Physicians wishing to make evidence-based treatment decisions for elderly patients may have to extrapolate clinical data from studies that have been conducted in a younger population. However, given that there are age-related changes that occur even in healthy elderly people, any such extrapolation may not be scientifically sound.1-3 Changes in physiological parameters that occur with increasing age, such as decreases in renal and cardiovascular function, blood flow and hepatic volume, make the disposition of drugs more variable in the elderly and predispose them to drug toxicities and adverse drug reactions.3 The result is that geriatric patients may not receive the newest therapies or may receive a treatment whose efficacy and safety in the elderly is not known.1-3

In a study published in the New England Journal of Medicine, Hutchins and colleagues5 determined the enrollment rate of cancer patients aged 65 years or older in clinical trials, and compared this with the corresponding rate of elderly cancer patients in the general population. Overall, the authors reported that the elderly were significantly underrepresented in all cancer trials and in 14 of the 15 types of cancer that were individually investigated.

Diet and Education in the Control of Diabetes in the Elderly

Diet and Education in the Control of Diabetes in the Elderly

Teaser: 

Tess Montada-Atin, RN, CDE
Care Leader

Marilyn Mori, RD
Lina Medeiros, MSW
Diabetes Education Centre,
Toronto Western Hospital
University Health Network
Toronto, ON

Diabetes is a chronic illness with significant short and long term complications.1 The Diabetes Education Centre (DEC) at the Toronto Western Hospital, University Health Network, supports people with diabetes, their family and friends to better understand and manage diabetes. The 1998 Clinical Practice Guidelines (CPG) for the management of diabetes in Canada, recommends initial and ongoing education for the person with diabetes as part of diabetes care and not just as an adjunct to treatment. Diabetes Education should be recognized as a life long commitment.2 Comprehensive management of diabetes should be planned around an interdisciplinary diabetes health care team,1-3 which can be through a DEC. To learn and use the varied complex skills required, people with diabetes need the support of such a team of expert professionals.1 Interdisciplinary interventions have been shown to improve glycemic control in the elderly. Studies have suggested that a team approach toward older people with diabetes improves blood glucose control, quality of life and adherence to therapy.3

Factors that affect glycemic control are diet, diabetes medications and exercise.

Vintage Advice

Vintage Advice

Teaser: 

Both the British Medical Journal and the Journal of the American Medical Association (JAMA) participate in the charming and instructive activity of reprinting short sections from their pages of 100 years ago. These pieces are often quaint, always entertaining and frequently outdated--but not always.

Many a time, and oft, in fact, they still speak to the heart of our clinical practice, even from over a century in which both the practice and face of medicine have changed so dramatically. For example, published in a recent issue of JAMA (Volume 182(17):1606i), and penned over a century ago by Dr. J.W. Bell in his prime as Professor of Physical Diagnosis and Clinical Medicine at the University of Minnesota, was an impassioned "Plea for the Aged".

It should be pointed out that, in 1899, geriatrics did not yet formally exist as a specialty and that Ignatz Naccher's seminal work, "Geriatrics: The Diseases of Old Age and their Treatment" would not come out in print for another 14 years. Marjorie Warren, considered the founder of modern hospital geriatrics in the UK for work in the 1940's, was then barely three years old.

Bell acknowledged that, despite the paucity of current American literature on the subject of the elderly, the French (Charcot, Pine) and British (Day, McLachlan) authorities had helped "to furnish the nucleus of our present knowledge of senile pathology". However, despite the interest of these eminent authorities, Dr. Bell offered a criticism that unfortunately is still quite relevant today: "The want of interest, as indicated by the scanty and fragmentary character of the literature on the subject, is largely responsible for the apathy existing today in our medical schools".

As we enter the new millenium, it must be acknowledged that there has been a modest improvement in the number of Canadian medical schools offering a course in geriatrics. Still, the growth is not at all proportional to the increase in the numbers of elderly. In 1899, less than 5% of the continent's population was over the age of 65. Today, that percentage has almost tripled and life expectancy has increased significantly throughout the developed world.

Despite his critique of the system, Bell understood the circular wars of the medical schools that still rage today. He offers that "It would seem criminal to even suggest that addition of another distinct course to the already overcrowded college [medical] cirriculum (sic)…." But he does offer two suggestions, the first of which still makes sense: "That the chairs of anatomy and physiology impart to the student the necessary primary instruction…". To the contemporary reader, his second suggestion may seem a bit quaint but it was obviously born out of desperation and the faint hope that colleagues might heed his plea. Here, Bell suggests that the "The chair of practice [Internal Medicine], or if deemed best, in order to contrast disease, the chair of pediatrics enlarge its scope and furnish the necessary…instruction…"

Were Dr. Bell to survey the situation today, he would also still have much room and justification for complaint. Despite improvements in our field, his words from one hundred years ago ring true today: "[the medical student] scarcely recalls reference by one of his teachers to old age, unless suggested in mitigation of the failure of some brilliantly planned but misjudged operation or equally ill-timed drug treatment".

JAMA's recent '100 Years Ago' column has helped us to realize that despite some improvement, at least in the field of treating the elderly, 'plus ça change; plus c'est le meme chose".

Dr. A. Mark Clarfield is the Chief of Academic Affairs at the Herzog Hospital in Jerusalem and on staff in the Division of Geriatric Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal.

Hypodermoclysis is a Valuable Method for Management of Dehydration in the Long-Term Care Setting

Hypodermoclysis is a Valuable Method for Management of Dehydration in the Long-Term Care Setting

Teaser: 

Sudeep Gill, MD and
Paula A. Rochon, MD MPH FRCPC
Baycrest Centre for Geriatric Care.

One of the goals of long-term care is to provide the patient with an appropriate level of care without unnecessarily disrupting his or her comfort and living situation. Older long-term care residents often suffer from acute intercurrent illnesses for which fluid replacement is an important component of treatment. If intravenous (IV) fluid replacement is not possible in these frail seniors, either because of regulations or due to staffing issues in the long-term care facility, it is often necessary to transfer them to an acute-care hospital setting.

In the institutionalized older patient, hypodermoclysis, which is the subcutaneous infusion of fluids, is an attractive alternative to the use of intravenous therapy for fluid replacement. It is a method that has been used since near the turn of the century. Although it has been employed with success for years at the Baycrest Centre for Geriatric Care, and a few other institutions, it remains under-recognized and underutilized as a valuable method for the management of mild to moderate dehydration in the long-term care setting.

Straightforward Principles for Management of the Diabetic Foot

Straightforward Principles for Management of the Diabetic Foot

Teaser: 

Leslie Goldenberg, BSc, MD, FRCPC
Internal, Geriatric and Podologic Medicine
Assistant Professor of Medicine, University of Toronto
Medical Director, The Walking Mobility Clinics
 

The first principle in the care of the diabetic foot is to recognize the primacy of prophylactic care. Indeed, an ounce of prevention is worth the proverbial pound of cure, even in the patient who appears to be low risk and does not suffer from peripheral neuropathy or vasculopathy. Physicians and other health care professionals have a critically important role to play when it comes to educating their diabetic patients regarding daily foot care, with particular attention paid to the care of skin, nail and callus, proper footwear and strategies to prevent foot trauma and infection. Diabetes remains the most common cause of non-traumatic limb loss, and there is considerable suffering and economic impact associated with the management of chronic diabetic foot pain and sepsis. Two-thirds of diabetic amputations follow complications that are related to foot ulcers.

Pressure platform studies demonstrate that the patient placing a diminished load on the toes is an early finding in diabetic neuropathy. This reduction in the load on the toes leads to a corresponding increase in metatarsal head loads. In addition, there is a shift of loading on the forefoot, away from the medial side, with increasing load now borne under the mid-foot, a characteristic of weakness of the longitudinal arch (mid-tarsal loading).

Unknown Cause, Unknown Cure: The Mechanisms of Insulin Resistance

Unknown Cause, Unknown Cure: The Mechanisms of Insulin Resistance

Teaser: 

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

Last year, the diabetes surveillance system reported that approximately 2 million Canadians suffer from diabetes, although as many as 600 000 of these might be unaware that they have the condition. It is now estimated that, by the year 2010, approximately four million Canadians will have diabetes and, that by the year 2020, there will be approximately 250 million people affected by type 2 diabetes, worldwide.1

What factors contribute to the development of this terrible disease? A few diabetic subjects suffer from type 1 diabetes mellitus, which is caused by failure of the pancreatic b-cells, and leads to an absolute loss of insulin. Type 2 diabetes is far more common and is swiftly increasing in prevalence in industrialized societies. It is believed that the main factor contributing to the increase in the number of patients with type 2 diabetes is the aging of the baby boomer population, a population that is becoming more sedentary and, as a result, more obese. An interesting question then is how do obesity and a sedentary lifestyle lead to the development of type 2 diabetes?

Type 2 diabetes is almost invariably preceded by the development of insulin resistance. Insulin resistance is defined as a state of reduced responsiveness to normal circulating concentrations of insulin, and is now recognized as a characteristic trait of type 2 diabetes.