MMSJER McMaster's Medical Research and Health Ethics Student Journal
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DiGeorge Syndrome
Research Articles Struggles in Caring for a Loved O n e with
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Alzheimer's Disease Tanzeel Rahman
Acne
The DiGeorge Syndrome 12 Nathalie Wong-Chong Acne Vulgaris: An Attack on the Skin and 18 the Psyche Deborah Kahan
Coronary Care Unit The Coronary Care Unit: Miracle of Modern 23 Medicine orTechnology Out of Control? Daniel Rosenfield Herceptin: Is it really worth it? 27 Mohammad Abdi Abdul Ghani Basith Mohammad Zubairi
About The McMaster Meducator
The McMaster Meducator may be contacted via our e-mail address: MeduEmail@learnlink.mcmaster.ca The McMaster Meducator adopts an educational approach to our publication. Despite or our mailing address: our efforts to ensure correctness, w e recognize that the publication may be subject to B.H.Sc. (Honours) Program errors and omissions. In light of these potential errors and new developments in the Attention:The McMaster Meducator medical field, w e invite you to partake in feedback and constructive discussion of the Michael G. DeGroote Centre for Learning and content herein for the purpose of furthering your understanding of the topic - in the Discovery R o o m 3308 name of education and discovery. Please enjoy the Meducator online experience! Faculty of Health Sciences Disclaimer: The views represented in the articles do not 1200 Main Street West necessarily reflect those of the McMaster Meducator and Hamilton, Ontario L8N 3Z5 should not be substituted for medical advice. http://www.meducator.org
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Issue 9 | November 2006
Meducator Staff
Dear Reader,
President One of the things I learned from working in a lab this summer is that science is a dynamic Jonathan Liu field. Top researchers are those that stay aware of cutting edge technologies and revolutionary discoveries in their fields. As a reader, I hope you are able to capitalize Vice-President on this excellent opportunity to gain an insight into issues faced by the medical community. Tyler Law The first issue this year brings together five different topics. Tanzeel R a h m a n provides an overview of Alzheimer's disease and its impact on caregivers, Nathalie Wong-Chong gives us a review of DiGeorge Syndrome and the importance of early diagnosis, Deborah Kahan reviews acne and its psychological impact, Dan Rosenfield surveys the modern Coronary Care Unit, and finally, M o h a m m a d Abdi, Abdul Basith, and M o h a m m a d Zubairi write about the efficacy of Herceptin. I would sincerely like to thank each writer for their time and effort.
Creative Director Crystal Chung VP Medical Research and Health Ethics Jeannette So Shama Sud Sarah Mullen Harjot Atwal Harman Chaudhry
VP Public Relations Our main goal, as it always has been, is to reach out to all Amandeep Rai undergraduates from diverse academic backgrounds. I want to thank the entire staff for helping create the new"MedWire" VP Web Design Fify Soeyonggo page. This will hopefully provide readers with an informative snapshot of medical news around the world. Furthermore, VP Communications Dr. Baron, an expert in microbiology at McMaster, has been Alexandra Perri kind enough to provide us with a review of the recent cases of botulism. VP Adminstration Navpreet Rana Each issue requires the coordinated effort of our writers, post-graduate editors, and staff members. I extend special thanks to all the contributors, especially:Tyler Law, for your reliabilityJunior Executives Jacqueline Ho and support; Crystal Chung, the mastermind for our amazing layout; Jeannette So, Shama Stephanie Low Sud, Harman Chaudhry, Harjot Atwal, and Sarah Mullen for maintaining high quality articles Siddhi Mathur and combined editing expertise; A m a n d e e p Rai, designer of the most witty ads; Jacqueline Ran Ran H o and Siddhi Mathur, for informative MedBulletins; Alexandra Perri, for putting together our first-ever article written by a professor; Fify Soeyonggo, our star webmaster and creative designer; Ran Ran and Stephanie Low, for your artistic talent; and finally, Navpreet Rana, for keeping our publication organized. I would also like to thank Dr. Del Harnish and the Bachelor of Health Science program for their generous support as w e enter into our fifth year. Post Graduate As an undergraduate publication, we value your feedback and I encourage all of you to post Editors in our LearnLink folder, or send your feedback to MeduEmail@learnlink.mcmaster.ca. Also, Dr. James Gillett challenge yourself and test your comprehension by trying our "MedQuiz" at the back of the MA, PhD publication and on our website, www.meducator.org. For those that enjoy the MedBulletins, keep an eye out for them on bulletin boards around campus. O n behalf of the publication Dr. James LVelianou team, w e hope you enjoy this issue! MD, FRCPC Yours Truly,
Dr. Peter Vlgnjevic MD, FRCSC Dr. Jia-Chi Wang M D , MSc, PhD
Jonathan Liu, B.A.Sc.
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Dr. Peter Whyte MD,^ISc,PhD
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Issue 9 | November 2006 "MEDJJMIW
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QjA study at Cornell im University suggested that • ^ the increase in reported ^ > cases of autism is related to ^ 3 a rise in cable subscriptions Ql across various states.
M D 2 and M D V I P are part of a group of new organizations offering "country-club medicine" to patients willing to pay more in the United States. Extra benefits include access to doctors 24/7, house calls, medical records on a wallet-sized CD, and much more.
Neurologists from the University of Florida recently discovered that brain damage in the frontal and temporal lobes improve artistic expression. This, however, decreased the emotional power of the artistic work.
Dr. Vincent Lam recently received the Giller Prize, a prestigious award given to outstanding novels written by Canadians. His novel titled "Bloodletting & Miraculous Cure" is a collection of stories involving ethical issues he has faced as an emergency physician.
A surgical t e a m in London, England, has received approval to perform full face transplants on patients with severe facial disfigurement. The full immunological and psychological consequences of this surgery are still uncertain.
Energy drinks are loaded with sugar and caffeine and have been linked to heart problems and caffeine addiction. Experts say prolonged use can lead to other illnesses but a healthy alternative might be difficult to introduce now.
Researchers at MIT and University of Hong Kong have developed a fluid composed of protein fragments that stop bleeding from damaged vessels within seconds. This is a promising new tool for managing bleeding during surgeries.
Curcumin, an active ingredient in curry, has been linked to the downregulation of certain genes in joints leading to its anti-inflammatory effects. Researchers are now studyingtheuseofcurcumin to treat inflammatory diseases such as asthma and multiple sclerosis. Several fatal cases of a bacteria called C.difficile have been reported by Preliminary experiments hospitals in Quebec. Researches believe that this for male contraceptives have begun on rats. new and powerful strain, Scientists in Italy and the not present in the hospital, United States demonstrated can be found in meat. that the drug "Adjudin" was able to reversibly induce infertility for a period of Scientists from the U K twenty weeks.The drug acts identified two c o m m o n on important cells involved proteins in 500 blood in spermatogenesis. samples taken from Alzheimer's patients. This is a promising step towards using blood The Canadian Institute markers for early for Health Information diagnosis and stabilization recently announced that of this condition. escalating healthcare
costs should continue to slow d o w n following the trend since 2000. This is a positive outlook for advocates of a sustainable public healthcare system.
T h e Ontario Court of Appeal has ruled that the provincial government cannot be sued by victims of the West Nile Virus in 2002. The plaintiffs claimed that the province did not properly inform citizens of the dangerous outbreak. This case addresses the accountability of public health officials.
New studies suggest that the h u m a n sclera, the white part of the eye, developed because of the importance of early human sociability and communication. Experimental evidence has shown that the whites of the eyes are used by humans to work out where an individual is looking. Other primates developed dark sclera and do not follow an individual's eyes.
A n e w study underlines a lack of family physicians to be a major problem in Canadian health care. The report postulates that nearly a five million Canadians do not have a family doctor, even after searching months for one. It highlights that the search for shorter wait time should include addressing this growing problem.
A n e w strain of H 5 N 1 avian influenza has been identified in China. www.meducator.org
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Issue 9 | November 2006 This is not viewed as a major cause for concern; however, it does support the need for vigilance and continued surveillance. The emergence of n e w strains of the virus confirms that it is increasing in prevalence in this area. These n e w strains also raise concerns about the effectiveness of current vaccines.
The United States and Switzerland have stockpiled an H5N1 bird flu vaccine produced by GlaxoSmithKline. Some researchers have expressed doubts regarding its efficacy based on a lack of pre-pandemic information and the rate of genetic change in the virus.
A report in India suggests that frequent cell p h o n e usage reduces the quantity and quality of sperm. M e n using cell phones for more than 4 hours/ day have 4 0 % less sperm than the average male.
A n e w test aims to reduce collateral d a m a g e from chemotherapy by suiting the type of treatment
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Botulism and Vegetable Juices: Should w e be concerned? By: Dr. Christian Baron
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S e v e r a l cases of "botulism" have recently been reported in Canada and in the US. This condition is quite rare these days, so that diagnosis was m a d e days to weeks after the patients were admitted to hospital. The victims suffered from a paralysis that progressively extended over their entire body. S o m e patients are still in hospital and can only breathe with the help of respirators as their o w n chest muscles are largely paralyzed. The paralysis will eventually wane, but it will take a long time until these patients can go back to their normal life. After the correct diagnosis had been made, an investigation identified the ingestion of vegetable juices from California as source of the problem. You m a y ask yourself what type of disease botulism is and w h y the diagnosis was so m u c h delayed? Could these cases have been prevented and do w e have reasons to be concerned about drinking vegetable juices in future? The recent cases of botulism were not due to an infection by bacteria, viruses or other microbial pathogens. Nonetheless, a bacterium is the source of the problem, Clostridium botulinum. This organism is m e m b e r of the Gram-positive branch of bacteria that have very thick cell walls. Clostridium botulinum produces the botulinum toxin, an extremely potent neurotoxin that blocks nerve transmission and is the main cause of food-borne botulism. In fact, botulinum toxin is considered to be the most potent naturally occurring poison on earth. O n e milligram is enough to kill one million guinea pigs and the lethal doses for humans is two micrograms. The diagnosis of botulism intoxication should have been straight forward, in principle, as the pathology has been known for a long time. However, this food intoxication is very infrequent in these days so that other causative reasons were considered first. The explanation for these cases is linked to the fact that Clostridium species have the ability to form heat-, droughtand radiation-resistant endospores in unfavourable environmental conditions. This survival form of the bacteria can persist over m a n y years without apparent growth and survives short periods of boiling. Once the bacteria encounters a favourable environment, and in the case of Clostridium it has to be free of oxygen. The spores germinate and the bacteria can grow and produce the toxin. Therefore, w e can hypothesize that spores of Clostridium botulinum, which can be readily found in soil, have likely entered the vegetable juice production process. D u e to incomplete sterilization of the production pipeline, a small number of the spores survived, the bacterial germinated in a local oxygen-free environment, and produced the small amounts of toxin that are the cause of these botulism cases. To conclude, these cases could have been prevented by better hygienic practice in food production. It is not likely that these particular juices or other products will produce worrisome risks in the future. Thus, there is no reason to fear botulinum intoxications in daily life, but it is good to be aware of the possibility, and fature medical professionals should be prepared to expect the unexpected.
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to the individual cancer. As explained in Nature Medicine, different chemotherapies work best against specific cancer cell types. The method describes identifying the specific cell type, and picking a chemotherapy based on that.
A research group in C a n a d a has identified a subset of stem cells as the culprits for colon cancer. This evidence supports the controversial belief that cancerous cells are derived from abnormal stem cells which are resistant to radiation.
Please email any suggestions to M e d W i r e @ learnlink.mcmaster.ca.
Issue 9 I November 2006
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Storing Soldier Sperm and the Many Unanswered Questions
MedBulletin by Jacqueline H o
Over the last few years, a n e w wave of preparation has been employed by soldiers heading off to battle in addition to legal and financial affairs. This practice is sperm banking. There are two main reasons for the increasing number of deposits by soldiers in sperm banks. First, it serves as a precautionary tactic against possible sterility attributed to weapons such as insecticides and nerve gas. Second, it allows the soldier's wife or girlfriend to bear his child if the soldier is killed in battle. In light of this development, several issues have yet to be addressed. One such concern is the lack of options for female w h o seek to preserve their reproductive abilities. In comparison with sperm banking, freezing eggs is a far more delicate and expensive procedure. Therefore, the cost of tens of thousands for egg preservation in comparison with the few hundred dollars for sperm banking means that preserving eggs is impractical to implement. There are further questions regarding the usage of a sperm from a deceased soldier. Should only wives and fiancees have the right to use to the sperm? Sperm banks currently limit the number of children a live donor can produce to ten, but h o w many children can a deceased donor legally father? Although technological advances have given soldiers options that were previously nonexistent, there are currently no rules, laws or legislation regarding the questions that have been raised. Nonetheless, loved ones ought to k n o w what will or will not happen w h e n trying to access the sperm of a deceased significant other. Caplan A. (2003). Soldier's sperm offers biological insurance policy But storing semen raises many unanswered questions. MSNBC. Retrieved November 11, 2006, from http://www.bioethics.net/ articles.php?viewCat=2&articleld=23
•
A cure for HIV, or not?
MedBulletin by Siddhi Mathur
Researchers at the University of Pennsylvania have treated five HIV patients with a disabled version of HIV. Though they had not responded to traditional therapies, they showed a positive response to the deactivated virus. The HIV levels in the patient's blood either decreased or stayed the same for about nine months; one participant displayed a significant drop in the virus count.
This disabled virus carries extra genetic material that blocks HIV production, which reduces the levels of HIV circulatin bloodstream. The patients were injected with an infusion of their o w n i m m u n e system, in which their T-cells were genetically modified with the manipulated versions of HIV. Such an alteration interferes with the reading of genetic material and hinders the process that HIV uses to reproduce in infected cells. Investigations have also focused on using lentiviruses as a vector for gene therapy. Lentiviruses also change the DNA by inserting themselves into infected cells, however, they are m u c h safer. Their ability to colonize cells slowly and persist afterwards offers promise to this emerging gene therapy vector.
However, the extensive manual labour required for these types of treatments is a barrier to their practical application. Furthermore, experts at the World Health Organization claim that the sample sizes for the trials done were not large enough and it could be years before gene therapy is d e e m e d effective and safe for HIV patients. Nonetheless, aforementioned developments are definitely an alternative to anti-retroviral drugs, and m a y develop into a useful tool for the sustained application of gene therapies.
(November 6, 2006). HIV gene therapy 'shows promise'. Retrieved November 10, 2006 from http-// news.bbc.co.uk/2/hi/health/6120042.stm
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Issue 9 I November 2006
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MedBulletin by Siddhi Mathur
T w o m e n in West Bengal, India have been arrested for selling expired pregnancy and HIV test kits. Sarda and Gansham, owners of M o n o z y m e , take no responsibility for the use of these kits. This mishap has resulted in infected people being given the thumbs-up to donate blood. Authorities located about 200,000 kits that were used past their expiration date. At least 117 people were given the wrong diagnosis w h e n taking an HIV test, and their infected blood is n o w being used in blood banks. In total, M o n o e n z y m e supplied over 200,000 kits and attempting to trace all the donated blood is nearly impossible. With the potential of infecting hundreds of people, no authority has taken the responsibility for this mishap. Owners Sarda and Gansham are pleading not-guilty to malpractice charges. Were they responsible for making sure all the kits being distributed were not expired? What roles or responsibilities do the doctors or personnel administering these kits have in checking the expiration date? O n e m a y wonder if they knew where and h o w to check for this vital information. Furthermore, should the patients have taken the onus to ensure that the equipment being used on them was in proper functioning condition? Resolving this issue will be particularly difficult as it revolves around the ethical misconduct of a chain of authority and m a y set a dangerous precedent. (October 30, 2006). Two accused over 'fake' HIV tests. Retrieved November 3, 2006, from http://news.bbc.co.Uk/2/hi/south_asia/6099064.stm
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Genetic T h e r a p y W i n s the 2 0 0 6
MedBulletin by Jonathan Liu
Nobel Prize for Medicine One of the most important recent advances in medical research is the ability for scientists to control gene expression mass scale through R N A interference (RNAi). For discovering this technique, Andrew Fire and Craig Mello were awarded this year's Nobel Prize in Medicine.
RNAi was demonstrated nearly fifteen years ago when a group of plant researchers decided to inject a gene to over-expre certain pigment. Rather than intensifying the colour, however, the plant lost its colour leaving scientists puzzled by this result. In 1998, Fire and Mello set out to explore w h y injecting more of a gene in R N A form caused silencing, which seemed counterintuitive. Using C.elegans as their model organism, the two discovered that double-stranded R N A (dsRNA) injections caused abnormal characteristics due to genes shutting off.
It was only years later that the mechanism for this phenomenon was elucidated. When dsRNA is injected into a cell, protei (dicer) in that cell recognize these foreign nucleic acids and chop them up. These fragments then bind to a complementing portion of m R N A inside the cell, causing the excision of those native sections. Consequently, the loss of m R N A stops the production of a crucial protein leading to abnormal traits. How does RNAi apply to us? This mechanism is inherent in all our cells to prevent the integration of foreign RNA, such as those from viruses. RNAi is currently being adapted as a novel way of managing HIV, cancer, hepatitis, and genetic disorders where certain gene expression is undesirable. Mello, C.C., & Conte, D. (2004). Revealing the world of RNA interference Nature 43 338341.
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Issue 9 | November 2006
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Struggles in Caring for a Loved O n e with Alzheimer's Disease
Tanzeel Rahman
L i k e m a n y chronic illnesses in the elderly, Alzheimer's Disease (AD) is a debilitating and extensive disorder that affects not only those directly afflicted with it, but also their friends and family. In a heart-felt personal account of both of her parents being diagnosed with Alzheimer's, a daughter and avid caregiver encourages us to ask m a n y important questions. Her n a m e is Marcell and her anecdotal article is entitled, "If I Only K n e w Then What I K n o w N o w " (Marcell, 2004). It was published in the Journal of the American Medical Directors Association and will be used as a stepping stone for assessing important geriatric issues such as patient-aggression, delayed diagnosis, and caregiver burnout. WHY DIAGNOSIS IS DELAYED AND ITS IMPLICATIONS FOR THE CAREGIVER Marcell begins her story by attributing her personal success to her parents' life-long support and encouragement. U p o n learning of her mother's deteriorating condition, her life changes drastically. W h e n she decides to take care of her mother, she finds that her father is not very supportive. Instead, he responds with anger, irrationality, and insists that he be the only caregiver. Marcell is shocked by his anger, as she has never seen her father behave this way. Yet, she rationalizes his behaviour by telling herself that she has never before gone against his wishes. Therefore, the notion of a geriatric disease being responsible for his behaviour never occurs to her. She is "stunned that numerous doctors, including the head of a psychiatric hospital [tell her] that [her father] is 'normal'for a m a n his age". Only after eighteen months and referral to a geriatric specialist does Marcell learn that both her parents have vascular dementia, and are in stage one Alzheimer's Disease.
Marcell's anecdote portrays the lack of A D awareness that currently exists on the part of both health care professionals and caregivers alike, and begs us to ask numerous questions: (1) W h y d o cases of delayed diagnoses occur in the first place? (2) W h a t are the implications of a late diagnosis? (3) W h a t can be done to prevent delayed diagnosis from occurring? A large multinational study reported that only 1 7 % of patients saw a doctor immediately after noticing symptoms, while 2 2 % of caregivers waited more than one year before making the first appointment. Clearly a considerable proportion of people are waiting longer than one year to seek medical attention. Consider a disease that the public is m o r e informed of, such as cancer; a waiting time of o n e year from w h e n s y m p t o m s b e c o m e evident to w h e n the patient sees a doctor would have dire consequences. While
Image from National Institute on Aging. http://www.niapublications orq/ pubs/portfolio/html/mind.htm (September 1st 2006).
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Issue 9 I November 2006
Image from National Institute on Aging, http://www.niapublications.org/ pubs/portfolio/html/biology.htm#longevity (September 1st 2006).
a change in personality and depression are usually considered hallmark characteristics of this disease, these traits were only evident in 3 9 % and 3 7 % of the complaints respectively (Wilkinson et al., 2004). These symptoms are also only evident in the early stages of Alzheimer's but can be easily overlooked. Additionally, a recent pilot study revealed that even w h e n clinicians suspect a diagnosis of Alzheimer's Disease, only 4 0 % regularly discuss such concerns with their patients (Johnson et al., 2000). The study reports that "although physicians are aware of the m a n y benefits of disclosure, they have concerns regarding the certainty of diagnosis, the patient's insight, and potential detrimental effects" (Johnson et al., 2000). This implies that factors, such as a lack of diagnostic confidence and apprehension of what the future might hold for the patient, can prevent doctors from acting responsibly in cases of Alzheimer's Disease. The implications of a late diagnosis are multiple-fold. Intuitively, a late diagnosis does not facilitate timely and effective decisions with respect to therapy, finances, and emotional adjustment. In Marcell's case, a delay of eighteen months resulted in great financial losses, as well as severe emotional and www.meducator.org
9 WEDML'M mental stress. Moreover, early diagnosis m a y allowthe patient more time to adjust to the idea of having the disease, providing a w i n d o w of opportunity to discuss a comprehensive care plan and direct the individual and family to appropriate resources (Johnson et al., 2000; Post & Whitehouse, 1995). Issues concerning driving safety, personal affairs of power of attorney, and decisions for future care can also be handled in a more timely manner (Johnson et al., 2000). A n earlier diagnosis and use of pharmacological and psychosocial therapy m a y also delay disease onset by two to five years (Marcell, 2004). From a financial perspective, keeping a person in stage I longer (which consists of a milder phase of symptoms) shortens the amount of time spent in full time care and nursing homes, decreasing the monetary burden considerably (Marcell, 2004). O n e prevalent reason for late reporting m a y be associated with the stigma surrounding dementia in our society. Such concerns show the pressing need for increased advocacy, education and awareness of Alzheimer's Disease a m o n g the general population as well as doctors. While in centuries past, it was c o m m o n for doctors to withhold medical information from patients due to the belief that disclosure m a y destroy a patient's motivation to live, recently emerging evidence demonstrates taking proactive steps as being more effective (Johnson et al., 2000). AGGRESSION IN ALZHEIMER'S DISEASE AND THE ROLE OF THE CAREGIVER A recurrent theme in Marcell's story is her father's unfounded aggression towards her and other caregivers. It is well k n o w n that 57-67% of dementia patients exhibit aggressive behaviour in the form of verbal outbursts, physical threats, and/or violence (Ryden, 1988; Hamel et al., 1990; Reisberg et al., 1989). Considering that caregiver abuse is a c o m m o n p h e n o m e n o n , one might be led to believe that only the patient is abusive toward the caregiver. Yet, a study of 342 caregivers revealed that 1 2 % had directed physically abusive behaviour in the form of pinching, shoving, biting, kicking, and striking towards the individual with dementia in their care (Coyne et al., 1993). Therefore, while evidence suggests that aggression a m o n g patients is c o m m o n , it is not restricted to them and m a y actually elicit similar behaviour from caregivers. A n increased report of violence in caregivers is easier to understand w h e n feelings of loneliness, helplessness, frustration and agitation that often accompany the daunting task of care giving are taken in account.
Issue 9 | November 2006
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changes of the caregiver. Even after the patient's death, the G P must help the caregiver in bereavement and making informed choices regarding their health Marcell's story informs us of the trials and tribulations (Brodaty & Green, 2002). Such research clarifies the of care-giving. Only a brief survey of the literature is highly important role oftheGP not only for Alzheimer's needed to confirm that burnout is a major problem patients but also their caregivers. amongst caregivers. Often described as living a 36-hour There are also ethnic differences in the day, burnout is attributed to a lack of job-appropriateperceived caregiver burden and the a m o u n t of stress training and minimal or nonexistent levels of positive one experiences. O n e of the most expansive reviews feedback (Mace and Rabins, 1999; Hubbell, 2002). on the topic summarizes the results of twenty-one Caregivers are often confined to their o w n homes, studies conducted on caregivers of African American, and therefore tend to be "isolated, frustrated, and Chinese, Chinese American, Korean, Korean American, exhausted" and "the household Alzheimer's caregiver Latino, and Caucasian descent as well as residents receives little respite from the d e m a n d s of his/her of 14 European Union countries. The review found responsibilities" (Hubbell, 2002). Similar to burnout that Caucasian caregivers report greater depression in the professional field, caregiver burnout is also and consider care giving more stressful than African characterized and measured in three key domains: American caregivers. Yet, Caucasian caregivers were depersonalization (maintaining distance from others), also more likely to be spouses and hence their close diminished personal accomplishment (a reduction in relationship with the patient might account for such the belief that what one is doing is important), and differences (Janevic et al., 2001). Additionally, the emotional exhaustion. Male caregivers are more likely report suggests that minority groups m a y have more to experience adverse burnout symptoms than female restricted access to resources and social support than as m e n are more likely to detach themselves, take an Caucasians. The authors also claim that differences objective approach to care giving, and tend to their in stress levels amongst different ethnicities m a y be patients with less emotional attachment than females. attributed to differing levels of baseline depression. Differences in coping strategies m a y also account for They conclude by suggesting that there are essential increased incidence of burnout in males. Giving care "differences in the stress process, in psychosocial around the clock imposes great stress on all aspects outcomes, and in variables related to service utilization of an individual's life. W h e n such efforts are only a m o n g caregivers of different racial, ethnic, national, rewarded by a further deterioration of the patient's and cultural groups" (Janevic et al., 2001). As there condition, the caregiver's feelings of disappointment are disparities in accessibility, this research has farare understandable (Hubbell, 2002). reaching implications in seeking help for, recovering Moreover, there a realso biological explanations from, or preventing burnout. These findings should for w h y burnout occurs. It is well documented that also be considered w h e n designing caregiver care giving is a very stressful experience, one that interventions and ensuring equal accessibility to renders individuals highly susceptible to endocrine support all caregivers. and immunological abnormalities. For example, family caregivers of A D patients are more likely to produce LOOKING INTO THE FUTURE lower levels of certain immunologically protective cytokines in response to influenza viruses, and take 2 4 % longer to heal from a c o m m o n w o u n d than Caregiving is an important aspect of caring for control patients (Prolo et al., 2002). A lower level of sufferers of dementia, and A D in particular, and it immunity translates into an increased susceptibility to has been analyzed on m a n y different dimensions. respiratory infections (i.e. influenza or pneumonia) for Increased advocacy and awareness of A D , open caregivers, which are major causes of hospitalization patient-caregiver-doctor communication, as well as and death a m o n g the elderly (Prolo et al., 2002). extensive positive-feedback and encouragement are Understanding such biological mechanisms and crucial steps in ensuring positive caregiver outcomes. further exploring them using pharmacotherapy m a y Since the majority of the current literature in geriatric help in reducing the caregiver burden. care is prone to methodological weaknesses (i.e. Understandably, the general practitioner (GP) small sample sizes and poor study designs), it would can play a pivotal role in preventing burnout. The G P also be desirable to see more rigorous studies being makes the diagnosis of the patient and is also vital in conducted to confirm current findings. providing encouragement to caregivers by referring Caregivers only enter detrimental states them to counseling, support groups, and support such as 'burnout' due to situational circumstances organizations and being vigilant in health-related and personal beliefs with no irreversible nervous CAREGIVER BURNOUT
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Issue 9 I November 2006 damage. Hence, society's investment in incorporating interventions to target caregivers is necessary. Doing so will reduce depression and caregiver burden, as well as the economic impact of Alzheimer's disease. N o amount of documentation will do justice to the overwhelming burden that caregivers face. Actions can be taken at the policy level to address such problems. Examples include providing more funding for effective and responsive h o m e care for families afflicted by AD. There also needs to be a greater range of support services and resources m a d e available to caregivers. Marcell's story gives us s o m e insight into the difficult experience of witnessing a loved one undergo drastic personality changes. It also enables us to explore h o w such an experience m a y leave family m e m b e r s and caregivers in a state of denial, which prevents acknowledgment of changes that influence the patient's and caregivers' lives. As Marcell's story has m a d e clear, such a response can drastically reduce the caregiver's quality of life, guide uninformed and ill-advised decisions, as well as lay the groundwork for articles like "If I Only K n e w then What I K n o w Now". E9 REFERENCES Brodaty, Henry. (2002). Who Cares for the Carer? The Often Forgotten Patient. Australian Family Physician. 31(9): 1-4. Coyne et al., (1993). The Relationship Between Dementia and Elder Abuse. The American Journal of Psychiatry. 150(4): 643-646. Eastley, R., & Wilcock, G. (1997). Prevalence and Correlates of Aggressive Behaviours Occurring in Patients with Alzheimer's Disease. International Journal of Geriatric Psychiatry. 12: 484-487. Farcnik, K., & Persyko, M. (2002). Assessment, Measures and Approaches to Easing Caregiver Burden in Alzheimer's Disease. Drugs Aging. 19(3): 203-215. Habermann, Barbara & Davis, Linda. (2005). Caring for Family with Alzheimer's Disease and Parkinson's Disease. Journal of Gerontological Nursing. 31(6): 49-54. Hamel et al. (1990). Predictors and consequences of aggressive behaviour by community based
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11 *MEDULiIl)/! dementia patients. The Gerontologist. 30: 206-211. Hubbell, L, & Hubbell, K. (2002). The Burnout Risk for Male Caregivers in Providing Care to Spouses Afflicted with Alzheimer's Disease. Journal of Health and H u m a n Services Administration. 25:115-132. Janevic, M., & Connell, C. (2001). Racial, Ethnic, and Cultural Differences in the Dementia Caregiving Experience: Recent Findings. The Gerontologist. 41 (3): 334-347. Johnson, H et al. (2000). O n Telling the Truth in Alzheimer's Disease: A Pilot Study of Current Practice and Attitudes. International Psychogeriatrics. 12(2): 221-229. Mace, N., & Rabins, P. (1999). The 36-Hour Day, 3rd ed. Baltimore: Johns Hopkins University Press. Marcell, Jacqueline. (2004). If I Only K n e w Then What I K n o w Now. Journal of the American Medical Directors Association. 5(2): 135-137. Noonan, A.E., & Tennstedt, S.L. (1997). Meaning in caregiving and its contribution to caregiver wellbeing. The Gerontologist. 37 (6): 785-794. Post, S. G., & Whitehouse, P. J. (1995). Fairhill guidelines on ethics of the care of people with Alzheimer's disease: A clinical summary. Journal of the American Geriatrics Society. 43: 1423-1429. Prolo et al. (2002). Psychoneuroimmunology - N e w Avenues of Research for the Twenty-First Century. Annals of the N e w York Academcy of Sciences. 966: 400-408. Spurlock, Wanda. (2005). Spiritual Well-Being and Caregiver Burden in Alzheimer's Caregivers. Geriatric Nursing. 26(3): 154-161. Sorensen et al. (2002). H o w Effective are Interventions with Caregivers? An Updated Meta-Analysis. The Gerontologist. 42(3): 356-372. Reisberg, et al. (1989). Stage specific incidence of potentially remediable behavioural symptoms in aging and Alzheimer's disease: A story of 120 patients using the BEHAVE-AD. Bulletin of Clinical Neurosciences. 54: 95-112. Ryden,M. (1988). Aggressive behaviour in persons with dementia living in the community. The Alzheimer Disease and Associated Disorder International Journal., 2:342-355. Teri, L. et al. (1989). Behavioural disturbance, cognitive dysfunction, and functional skill: Prevalence and relationship in Alzheimer's Disease. Journal of the American Geriatric Society.. 37: 109-116. Wilkinson etal. (2004).The Role of General Practitioners in the Diagnosis and Treatment of Alzheimer's Disease: A Multinational Survey. The Journal of International Medical Research. 32: 149-159.
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*MEDMUIO/{ 18
Acne Vulgaris: An Attack onthe Skin and the Psyche
Deborah Kahan
"/ don't look in mirrors.... I am like a vampire-Kahn, 2004). Furthermore, 2 0 % of newborns develop acne, 2 5 % of sufferers will have permanent scars and -I shy away from mirrors. I comb my hair using only 1 6 % of adolescents seek medical treatment for my silhouette on the wall to show the outline their skin (Arnold, 2006). of my head. I have not looked myself in the eyes Acne is not just a disorder that affects the skin; in years, and it is painful not to be able to do its psychological affect is also well documented. that, and that is a direct result of acne, the acneA recent study on depression done by the University of Western Ontario's Department of Psychiatry surveyed scarring."-- Acne sufferer
480 patients with dermatological disorders such as localized hair loss, eczema, acne, and psoriasis. They found that 5.6% of patients with non-cystic facial "There is no single disease which causes more acne had suicidal ideation. Out of all the cosmetically disfiguring disorders studied, only patients with severe psychic trauma, more maladjustment between parents and children, more general insecurity psoriasis were more likely to have suicidal thoughts. and feelings of inferiority and greater sums ofThe patients with psoriasis and mild to moderate acne also rated highest on the Carroll Rating Scale for psychic suffering than does acne vulgaris." Depression, both scoring within the range of clinical --Sulzberger & Zaldems, 1948 depression (Gupta & Gupta, 1998). An American survey (AcneNet, 2006) of 479 acne patients between the ages of 16 and 63 found that acne severity was significantly associated with poorer social interactions and lower quality of A c n e is commonly viewed as a transitory cosmetic life (Krejci-Manwaring et al., 2006). In a study done grievance that afflicts adolescents. It is almost in Oxford, 111 acne patients reported psychological, a rite of passage at this stage of life, as c o m m o n social, and emotional problems equal in severity as m o o d swings and voice changes. Acne vulgaris, to patients with back pain, arthritis, epilepsy, and however, can last well beyond adolescence, and its chronic disabling asthma. They concluded that acne is repercussions often make it a m u c h more terrible not a trivial disease and should be treated accordingly disease than many suppose. This article reviews the (Mallon etal., 1999). connection between acne and depression, as well as In rare cases, patients can develop acne discusses community awareness, acne formation, and dysmorphia, a form of Body Dysmorphic Disorder treatment options. (BDD), whereby the patient develops an obsession with the condition of their skin, sometimes checking EPIDEMIOLOGY AND PSYCHOLOGICAL IMPLICATIONS their face in the mirror obsessively. A Turkish study involving 159 acne patients discovered that 8.8% were OF A C N E VULGARIS diagnosed with BDD, and 21.4% of patients with acne Acne vulgaris affects roughly 80% of female and 90% and B D D were found to have associated psychiatric disorders. All of the patients were unaware of their of male adolescents. It is generally worse in adolescent treatment options (Yazici et al., 2004). Seeking males and tends to subside as people reach their late treatment for acne has shown to significantly improve 20s, however, 3 % of m e n and 12 % of w o m e n over the m o o d and psychological function of most patients the age of 30 are still plagued by the disease (Erlich & (Krowchuck et al., 1991). (AcneNet, 2006)
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19 *M ED m y ii ii MEDICAL CARE Studies suggest that patients have limited knowledge of acne and its treatment. For example, in a survey of Croatian acne patients, 6 6 % thought that the disease would improve immediately after the first treatment (Brajac et al., 2004). A British study found that less than one-third of patients with definite acne (12+ lesions) had sought medical help (Smithard et al., 2001). Acne patients from low-income households and rural areas are less likely to receive intense treatment such as dermatological referrals and oral isotretinoin (Haider et al., 2006). ACNE FORMATION Several factors contribute to acne formation. High concentrations of male sex hormones (androgens) result in overactive sebaceous glands. A high rate of keratin formation in the skin's outer layer blocks the openings of the sebaceous glands w h e n the keratinized cells die. This results in a blocked plug (comedone) and a buildup of sebum under the skin, creating a perfect environment for the proliferation of Propionibacterium acnes (P. acnes) bacteria. The plugs m a y b e c o m e blackheads if they are pushed to the surface and oxidized to a black colour, or whiteheads, which remain beneath the surface. The surrounding skin becomes inflamed as the i m m u n e system attempts to fight the bacterium. A superficial, elevated area of inflammation is classified as a papule, while an elevation with a central area of pus is called a pustule (Figure 1). A nodule or cyst is a deeper, raised area which m a y be draining. The severity of acne is classified as follows: mild if less than 30 noninflammatory comedones are present, moderate if 30-125 lesions consisting of papules and pustules are present, and severe if more than 125 lesions consisting of nodules and cysts are present. ASSESSMENT AND MANAGEMENT
Assessment One evidence-based guideline recommends that on any office visit, whether acne-related or not, the physician should inquire about acne and its impact on the patient's m o o d and social life. Before treatment is undertaken, the physician should look for underlying contributing factors. Acne can be exacerbated by medical conditions that cause excess androgen such as polycystic ovarian disease. Cosmetics that block pores also contribute to this condition if they are oil-based.
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"MEDMtylW 20 Management
but also has the highest risk for adverse events suc birth defects afflicting the brain and heart, thus, this The physician should work with the patient to develop drug is reserved for severe nodulo-cystic acne. The link between Accutane and depression or suicide is a treatment plan. The goals of the plan are to clear controversial. As of 2003, the American Food and Drug the acne, avoid scarring, and reduce psychological Adminstration had received 173 reports of suicide distress. There are a wide variety of treatment options in patients taking Accutane (Hull & D'Arcy, 2003). available. Mild cases of acne m a y be treated with Accutane m a y decrease brain metabolism in the over-the-counter products such as salicylic acid and orbitofrontal cortex, an area of the brain that controls benzoyl peroxide. Salicylic acid, a beta-hydroxy acid, depressive symptoms (Bremner et al., 2005). Yet, there is keratolytic. It softens and sheds the outer layer of have also been m a n y studies showing no connection the skin to prevent the clogging of pores. Benzoyl between Accutane usage and depression. One peroxide is an antibacterial cream with mild keratolytic review of nine studies, however, found a prevalence properties. Alpha-hydroxy acids, such as glycolic acid and mandelic acid, m a y also be useful in shedding the outer layer of the epidermis and improving skin texture and tone. SOCIAL SIDE EFFECTS FOR A C N E SUFFERERS Antibacterial topicals such as clindamycin and erythromycin are equally effective. In one study, a 1 % clindamycin solution was efficacious in treating • Refusal to make eye contact inflammatory acne as one tetracycline capsule taken • Difficulty forming and keeping relationships twice daily (Griffith, 2004). Topical retinoids such as • Heavy use of m a k e u p and hair growth to tretinoin, adapalene, and tazoretene work best on cover face comedonal acne. Topical creams are generally less • Shyness and introversion invasive and irritating than gels. Combinations of • Social reclusion the aforementioned drugs m a y also be used. Oral • Social phobia antibiotics such as tetracycline, minocycline, and • Decreased self confidence doxycycline are effective against Propionibacteria. • Refusal to play sports requiring changing Possible side effects include photosensitivity, rooms, where truncal acne is exposed antibiotic resistance, and overgrowth of yeast. The usual course of treatment is eight to twelve weeks. If • Refusal to g o to school resulting in poor the acne relapses while tapering, the dose should be academic performance increased provided that there are no side effects. • Increased sick days Oral contraceptives are anti-androgenic and • Reduced career choice d u e to appearance pro-estrogenic, resulting in decreased production • Less success in job applications of sebum. The most effective combinations are • Anger and aggression cyproterone acetate (Diane-35) and drospirenone • Depression and ethinyl estradiol (Yasmin). Spironolactone, a • Excessive spending for treatments potassium-sparing diuretic, is a potent anti-androgen. In w o m e n , it is often taken with oral contraceptives Table 1: A list of the following side effects reported from acne sufferers because it causes irregular periods and feminization (AcneNet, 2006). of the fetus. Overall, evidence suggests that oral antibiotics are about as effective as hormonal agents. Treatment plans should be tailored to the individual. of depression of 1 to 11 % in Accutane patients which A w o m a n in her late twenties most likely has was similar to suicide rates for the oral antibiotic hormonally induced acne, and should receive either control groups. The study concluded that Accutane oral contraceptives or spironolactone. An adolescent was not associated with an increase in depression male, however, would receive oral antibiotics since (Marquleing et al., 2005). Depression and suicidal spironolactone can cause breast enlargement. ideation are c o m m o n in adolescents, particularly in Accutane (isotretinoin) is a synthetic derivative those with severe acne, and no solid conclusion can of vitamin A. Its exact mechanism of action is unknown, be formed as to the relationship between Accutane but it appears to alter D N A transcription causing and its psychiatric effects (Stragan & Raimer, 2006). decreased sebaceous secretion. It also suppresses Other therapeutic options include alphakeratin production and P. acnes growth in the skin hydroxy acid and microdermabrasion, both used to ducts. Accutane remains the most effective treatment reduce scarring and comedonal acne. C o m e d o n e s
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Issue 9 | November 2006 can also be manually removed using an extractor. Phototherapy has produced promising results in several controlled trials (Charakida et al., 2004). Zinc and pantothenic acid were found to be effective, but further research is required before they can be recommended for routine use.
Figure 2: A patient with treatment-resistant cystic acne. (Koo & Lebwohl, 2001).
PSYCHOLOGICAL MANAGEMENT The physician should enquire about the impact of the patient's acne on his or her m o o d and social interaction (Table 1). Dr. Karen Scully, a former assistant professor in the Department of Medicine at McMaster University, states: "As health professionals, the link between acne and depression should be a wake-up call to us. W e need to be asking teenagers about their emotional state w h e n we're treating their acne. Parents should be asking too" (Doctor's Guide, 2000). Patients should be encouraged to comply with treatment, as it often takes several months for its full effects to become apparent. Patients should be reassured that the physician will work systematically to find the most effective and safe treatment option and also remain encouraged to focus on the positive results of treatment rather than agonize over every breakout. Judicious use of make-up for social occasions can help encourage social engagement. Patients with clinically significant anxiety or depression m a y require referral to a pediatrician or adolescent psychiatrist. FUTURE MANAGEMENT OF ACNE Acne is a common skin disorder caused by overproduction of sebum, and bacterial growth in plugged pores. Studies have demonstrated that acne can affect more than just the patient's skin. M a n y
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acne patients do not seek prompt medical attention despite evidence that medical treatment is effective at clearing acne, preventing scarring and improving psychological outcomes. Treatment options include benzoyl peroxide,topical retinoidsandantibiotics,oral antibiotics, oral contraceptives and spironolactone, and oral isotretinoin. W h e n physicians examine adolescents, acne should be one of the things to look for and ask the patient about. If parents express concern about their adolescent's m o o d or social interaction, the physician should consider acne as a possible contributing factor. It should be identified and treated promptly, and psychological support must be a factor in the treatment plan. Failure to identify and treat acne could m e a n missing a potentially crucial factor in the patient's mental and social health. Acne can be more than just a transient disease. If it causes depression in people at a young age, it has the potential to affect the outcome of their entire lives (Figure 2). With acne, the mental scars m a y be just as devastating as the physical scars. H REFERENCES
Acne Management. (2006). National Guideline Clearinghouse. Retrieved August 29, 2006, from http://www.guideline.gov/summary/summary. aspx?doc_id=9367. AcneNet: The Social Impact of Acne. American Academy of Dermatology. Retrieved August 29, 2006 from http://www.skincarephysicians.com/ acnenet/socimpct.html. Arnold, M.A. Dermatologic Surgery Specialists. M a n a g e m e n t of Acne and Rosacea. Retrieved August 29, 2006, from http://members.aapa.org/ aapaconf2006/syllabus/6029ArnoldAcne.pdf. Brajac,l.,Bilic-Zulle,L.,Tkalcic,M.,Loncarek,K.,&Gruber, F. (2004). Acne vulgaris: myths and misconceptions a m o n g patients and family physicians. Patient Educ Couns, 54(1), 21-25. Bremner, J.D., Fani, N., Ashraf, A., Votaw, J.R., Brummer, M.E., Cummins, T., Vaccarino, V., G o o d m a n , M.M., Reed, L, Siddiq, S., & Nemeroff, C.B. (2005). Functional brain imaging alterations in acne patients treated with isotretinoin. A m J Psychiatry, 162(5), 983-991. Charakida, A., Seaton, E.D., Charakida, M., Mouser, P., Avgerinos, A., & Chu, A.C. (2004). Phototherapy in the treatment of acne vulgaris: what is its role? A m J Clin Dermatol, 5(4), 211-216. Cotterill, J.A., & Cunliffe, W.J. (1997). Suicide in dermatological patients. Br J Dermatol, 137(2), 246250. Doctor's Guide (2000). Scientific evidence supports
"MEDJlUlDIi 22 link between acne and depression. Retrieved August 31, 2006, from http://www.pslgroup.com/ dg/1 CF06E.htm. Erlich, M., & Kahn,T. (2004). Acne and Related Disorders. Retrieved August 31, 2006, from http://www. clevelandclinicmeded.com/diseasemanagement/ dermatology/acne/acne.htm. Griffith, R. (2004). Getting Control of Acne. Retrieved August 31, 2006, from http://www.healthandage. com/public/health-center/38/article/1694/GettingControl-of-Acne.html. Griffith, R., Hull, PR., & D'Arcy, C. (2003). Isotretinoin use and subsequent depression and suicide: presenting the evidence. A m J Clin Dermatol, 4(7), 493-505. Gupta, M.A., & Gupta, A.K. (1998). Depression and suicidal ideation in dermatology patients with acne, alopecia, areata, atopic dermatitis and psoriasis. Br J Dermatol, 139(5), 846-850. Haider, A., Mamdani, M., Shaw, J.C, Alter, D.A., & Shear, N.H. (2006). Socioeconomic status influences care of patients with acne in Ontario, Canada. J A m Acad Dermatol, 54(2), 331-335. Johnson, B., & Nunley, J. (2000). Use of Systemic Agents in the Treatment of Acne Vulgaris. Retrieved August 21, 2006, from http://www.aafp.org/ afp/20001015/1823.html. Koo, J., & Lebwohl, A. (2001). Psychodermatology: The Mind and Skin Connection. Retrieved August 29, 2006, from http://www.aafp.org/ afp/20011201/1873.html. Krejci-Manwaring, J., Kerchner, K., Feldman, S.R., Rapp, D.A., & Rapp, S.R. (2006). Social sensitivity and acne: the role of personality in negative social consequences and quality of life. Int J Psychiatry Med, 36(1), 121-30.
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Krowchuk, D.P., Stancin, T., Keskinen, R., Walker, R. Bass, J., & Anglin, T.M. (1991). The psychosocial effects of acne on adolescents. Pediatr Dermatol, 8(4), 332-338. Mallon, E., Newton, J.N., Klassen, A., Stewart-Brown, S.L, Ryan,T.J., & Finlay, A.Y. (1999). The quality of life in acne: a comparison with general medical conditions using generic questionnaires. Br J Dermatol, 140 (4), 672-676. Marquleing, A.L., & Zane, L. (2005). Depression and suicidal behaviour in acne patients treated with isotretinoins systematic review. Semin Cutan M e d Surg, 24(2), 92-102. Smithard, A., Glazebrook, C , & Williams, H.C. (2001). Acne prevalence, knowledge about acne and psychological morbidity in mid-adolescence: a community based study. Br J Dermatol, 145(2), 274-279. Stragan, J.E., & Raimer, S. (2006). Isotretinoin and the controversy of psychiatric adverse effects. Int J Dermatol, 45(7), 789-799. Tan, J.K., Vasey, K., & Fung, K.Y (2001). Beliefs and perceptions of patients with acne. J A m Acad Dermatol, 44(3), 439-445. Walker, N., & Lewis-Jones, M.S. (2006). Quality of life and acne in Scottish adolescent schoolchildren: use of the Children's Dermatology Life Quality Index (CDLQI) and the Cardiff Acne Disability Index (CADI). J Eur Acad Dermatol Venereol, 20(1), 45-50. Yazici, K., Baz, K., Yazici, A.E., Kotkurk, A., Tos, C, Demirseren, D., & Buturak, V. (2004). Diseasespecific quality of life is associated with anxiety and depression in patients with acne. J Eur Acad Dermatol Venereol, 18(4), 435-439.
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Issue 9 I November 2006
The Coronary Care Unit: Miracle of Modern Medicine or Technology Out of Control?
I w*
Daniel Rosenfield
T h e Coronary Care Unit (CCU), created in the 1960s, has changed substantially since its inception. Originally designed strictly to treat heart attack patients in imminent danger, it is used today as an observation unit and treatment facility, incorporating many advanced technologies not originally designed for use in the CCU. The clinical effectiveness of the C C U has been understudied, and thus, represents a perfect case study for examining the proliferation of technology in the medical field, and its respective benefits and drawbacks. This article aims to investigate the development of the CCU, and address the question of what lessons can be learned through an assessment of the CCU's evolution. While the C C U is undoubtedly a miracle of modern medicine, w e must remain vigilant
w h e n assessing n e w technologies, using the best evidence-based techniques to assure that resources and m o n e y are not being utilized in practices that are inefficient. INTRODUCTION When we see doctors reviving heart attack patients or injecting patients with'miraculous'drugs on television, these patients are almost always located in the Coronary Care Unit (CCU) of the hospital. The C C U — created during the 1960s after technological advances such as the invention of the electrocardiogram (EKG) and the external defibrillator—has proven to be one of the most glamorized aspects of modern medicine. The C C U represents a microcosm of m a n y technologies found within the medical world, and according to Naggan, is a perfect case study in examining the proliferation of technology in medicine. This is because it is a complex system that combines several components of n e w technologies. The C C U has also been in operation for a number of years, becoming a staple in modern hospitals despite the lack of studies to evaluate its effectiveness—a characteristic of m a n y modern technologies (Naggan, 1986). This article will examine the history of the CCU, emphasizing that although initially heralded as a technological breakthrough capable of changing the face of cardiac care, its value and effectiveness should be more thoroughly scrutinized. CARDIAC CARE AND THE DEVELOPMENT OF THE CCU
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The history of the treatment of cardiac conditions (s as Acute Myocardial Infarctions (AMI)) has changed substantially over the past hundred years. In the early 1900s, the treatment of AMI "was characterized by benign neglect"(Khush, Rapaport, & Waters, 2005). Patients w h o arrived at hospitals were placed on bed rest, and often sedated. They were generally removed
tvlEDm'LSOEi 24 from the noisy areas, such as nursing stations. By the 1920s, it was recommended that physicians do everything in their power to "spare the patient any bodily exertion" for fear of cardiac arteries rupturing (Wearn, 1923). Patients were often treated with stimulants such as camphor and caffeine in order to help prevent heart block and hypertension, both potential complications of AMIs. In 1928, a journal article published in The Lancet reported that, Dr. Parkinson and Dr. Bedford advocated for morphine to alleviate pain, and for abstention from any chemicals that m a y cause hypotensiveness. Additionally, rest was paramount, as "the return to ordinary life [should be] postponed as long as possible" (Parkinson & Bedford, 1928). Mortality from AMI at this time was estimated at 3 0 % (Braunwald, 2003). Cardiac care remained largely unchanged until 1947 with the "discovery that ventricular fibrillation could be reversed"1. This discovery, m a d e serendipitously by Dr. Beck during an open chest surgery in 1947, was later confirmed on another patient indicating that physicians could resuscitate a patient with a previously fatal Ml. From this point on, AMIs and cardiac arrests were treated with cardiac massage and internal electrical defibrillation until the next leap in technology led to the external cardiac defibrillator. Invented in 1956, the external cardiac defibrillator provided the impetus for the creation of the modern CCU. In 1960, Dr. Kuwerhoven and colleagues at the Johns Hopkins School of Medicine "demonstrated the efficacy of combining mouthto-mouth breathing with sternal compression and external electrical defibrillation" in aiding an ailing patient (Khush, Rapaport, & Waters, 2005). With this final step, the C C U was created. The modern C C U was the brainchild of a Scottish physician n a m e d D e s m o n d Julian, w h o in 1961, envisioned a hospital unit designed specifically for cardiac care encompassing the following four criteria: a) Continuous electrocardiographic monitoring with arrhythmia alarms b) Cardiopulmonary resuscitation with external ventricular defibrillation c) Admission of patients with AMI to a single unit of the hospital where trained personnel, cardiac drugs and specialized equipment were available, and d) The ability of trained nurses to initiate resuscitation
Ventricular Fibrillation (VF) is a condition that occurs when the lead to a drop in blood pressure, and often, to cardiac arrest.
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These principles were later adopted internationally in select hospitals, where their initial results were challenged by both physicians and medical journals. Within six years, however, with the continued persistence of Dr. Julian and a limited n u m b e r of studies indicating the success and lower mortality rates of those treated in CCUs, "virtually every community hospital in the United States and Canada had either established a formal C C U or designated several beds for the specific care of patients with A M I " (Bahr, 2000). In Canada, the first C C U was established in the 1960s by Dr. Robert MacMillan and Dr. Ken Brown at the Toronto General Hospital, which is n o w part of the University Health Network (University Health Network, 2005). The C C U continued to evolve, and began to include more complex therapies, as well as drugs designed to prevent arrhythmias. In addition, it b e c a m e accepted in the medical community that the C C U was the only w a y to treat nearly all types of cardiac conditions. This was in spite of warnings by s o m e cardiologists that C C U s were being used haphazardly and inefficiently (Burch & Giles, 1971). By the late 1960s, doctors were publishing studies demonstrating that certain drugs should be administered in the C C U and advocating for the use of m o r e invasive and technology-intensive procedures within the unit. These approaches gained tremendous support for m a n y years until a landmark study w a s released in 1989 indicating that m a n y of the drugs that suppressed ventricular arrhythmias actually"increased mortality in postmyocardial infarction patients" (Khush, Rapaport, & Waters, 2005).
muscle no longer pumps in a coordinated fashion. This
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Issue 9 | November 2006
25 "MEDUIL'JIlll
m a n y biases and confounding factors. For example, observational studies that examined mortality before In the past twenty years, other new technologies have the introduction of CCUs compared to after their implementation were criticized (and subsequently m a d e their w a y into the CCU, including advanced discounted) due to changes in the labelling of AMIs2. catheters, n e w drug treatments, and an abundance In fact, the only two studies measuring the quality of interventional cardiological methods. W h a t is of CCUs found that there was no difference in results important to note is that according to physicians, w h e n comparing C C U care to h o m e care. Mather's many of these interventions do not actually belong in study showed that it was actually safer to stay at h o m e the CCU. Given the current hospital structure, however, than to go to the C C U (Mather et al., 1971 )3. these n e w treatments and technologies have m a d e O n e reason for this seemingly counterintuitive their h o m e in these ever-growing units. M a n y of result is, as Mather argues, that CCUs produce the these n e w interventions are k n o w n as 'interventional same arrhythmias the experts are treating. In other cardiology', and belong in 'step down' units. However, words, the conditions of the CCU, and the subsequent "the difference in care between the C C U and cardiac stress on patients generated by such an environment, 'step down' units has blurred, which has led to great have resulted in increased abnormal heart rhythms. debate on the continuing utility of large, specialized Thus w h e n they are successfully treated, CCUs claim CCUs" (Khush, Rapaport, & Waters, 2005). In addition, to have saved patients'lives, w h e n in reality, had they with the advent of primary percutaneous coronary been at h o m e , the patients would not have been in intervention, which lowers mortality and morbidity, danger in the first place (Cox, 1978). It is important many patients with AMIs no longer need to be in a to note, however, that Mather's interpretation is based formal C C U (J. Velianou, personal communication, on studies conducted over thirty years ago, and the October 27, 2006). treatment of AMIs has changed drastically since then. O n e concern that emerged in the 1980s and PROBLEMS AND ISSUES IN THE CCU remains present today is the admission of suspected As previously noted, the invention and implementation AMI patients: those w h o have symptoms that m a y or m a y not be the result of an Ml. Estimates have pegged of CCUs was not without controversy. The primary this figure at approximately 7 0 % of all C C U admissions, issue arose from the fact that little research had been and these patients are proving to be a significant done to test the effectiveness of the CCUs (compared strain on the healthcare system, both financially and to traditional in-hospital care or h o m e care). Naggan in terms of h u m a n resources (Fineberg, Scadden, & posits that the unprecedented adoption of CCUs and Goldman, 1984). the speed at which they proliferated was due largely Despite these criticisms, it is important to note to the fact that before the invention of the CCU, little that the C C U is an integral part of hospitals. Not all could be done to treat AMI patients. In other words, measures require the support of research evidence "this proliferation probably reflects the frustration at before implementation. M a n y patients suffering h o w little could be done for Ml patients [...] rather cardiac distress or failure must be put on ventilators than comprising scientific proof of C C U effectiveness" and treated with other specialized equipment. For (Naggan, 1986). Despite the few studies available these individuals, the tertiary care available in the examining the issue, most have concluded that CCUs C C U is undoubtedly necessary and considered "good offer no significant reduction in mortality rates, as practice". At the same time, advances in medical compared to rural hospitals without these complex technology allow physicians to postpone death, units (Goldman, 1982; Hill et al., 1978). That said, regardless of the subsequent quality of life (Molloy certain conditions were treated more successfully in et al., 1991). Individual beliefs, as well as the wishes urban hospitals with CCUs than rural ones (Marshall of their patients and families, guide physicians' uses etal., 1968). of modern and frequently invasive technology. In M a n y researchers have also c o m m e n t e d addition to cost-effectiveness, ethical issues such on the lack of "good" studies (randomized clinical as defining "end-of-life" should be considered in the trials) examining the effectiveness of CCUs. The evaluation of the clinical value of CCUs. existing studies have largely been criticized for their THE ROLE OF THE MODERN CCU
2
Afterthe introduction of CCUs, the classification (labeling) of AMI became different, and as a result, many more cases were classified as AMIs. Before CCUs, these cases would not have been called such, and as a result, the legitimacy of the study was undermined. 3 That being stated, this study is somewhat dated, and should you or someone you know experience heart-attack 4ike symptoms, consult a physician. www.meducator.org
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Issue 9 | November 2006
Care of patients with a low probability of acute myocardial infarction. Cost effectiveness of alternatives to coronary-care-unit admission. The CCU exemplifies an inextricable link between N.EnglJ.Med., 310, 1301-1307. medicine and technology. Developed in the Goldman, L (1982). Coronary care units: A perspective 1960s w h e n almost nothing could be done for AMI on their epidemiologic impact. patients, the CCU today represents an amalgamation International Journal of Cardiology, 2, 284-287. of technological advancements and esoteric Hill, J.D., Hampton, J.R., & Mitchell, J.R.A. (1978). professional knowledge. However, its clinical A randomized trial of h o m e versus hospital effectiveness has not been closely studied, and m a n a g e m e n t for patientes with suspected previous studies are suspect due to high degrees myocardial infarction. The Lancet, 1,837-841. of bias and other confounding factors. While this Khush, K. K., Rapaport, E., & Waters, D. (2005). The article does not discredit the coronary care unit, history of the coronary care unit. CanJ.Cardiol., 21, its intent is to stimulate discussion and research in 1041-1045. order to question its value today. The startling lack of Marshall, R.M., Blount, S.G., & Genton, E. (1968). Acute contemporary research into the utility and success of myocardial infarction: Influence of a coronary care CCUs m a y be a symptom of a problem that affects the unit. Archives of Internal Medicine, 122, 472-475. medical community at large - that technologically Mather, H. G., Pearson, N. G., Read, K. L., Shaw, advanced practices are rarely questioned and their D. B., Steed, G. R., Thorne, M. G. et al. (1971). effectiveness rarely examined. W e must remember Acute myocardial infarction: h o m e and hospital that even though a specific technology m a y be the treatment. Br.Med.J., 3, 334-338. newest and most advanced, it is not necessarily the Molloy, D. W., Guyatt, G. H., Alemayehu, E., Mcllroy, most efficient. In an era of spiralling healthcare costs W., Willan, A., Eisemann, M. et al. (1991). Factors and finite h u m a n resources, this message should be affecting physicians' decisions on caring for an heeded carefully. ยงQj incompetent elderly patient: an international study. CMAJ., 145, REFERENCES 947-952. Bahr, R. D. (2000). Chest pain centers: moving toward Naggan, L. (1986). Epidemiologic methodology in evaluating health technology. IsrJ.Med.Sci., 22, proactive acute coronary care. Int.J.Cardiol., 72, 179-182. 101-110. Parkinson, J., & Bedford, E. (1928). Cardiac infarction Braunwald, E. (2003). The Simon Dack lecture. and coronary thrombosis. The Lancet, 1,4-11. Cardiology: the past, the present, and the future. University Health Network. (2005). Research Institute's J.Am.Coll.Cardiol., 42, 2031-2041. Firsts and Breakthroughs. Retrieved October 30, Burch, G.E., & Giles, T.D. (1971). A Study of the 2006, from Efectiveness of the Coronary Care Unit. Southern http://www.torontodiscoverydistrict.ca/Page.asp? MEdical Journal, 64(4), 435-440. ldPage=3778&WebAddress=DiscoveryDistrict. Cox, J. (1978). [Letter to the editor]. British Medical Wearn, J.T. (1923).Thrombosis of the coronary arteries Journal, 2, 431. with infarction of the heart. American Fineberg, H. V., Scadden, D., & Goldman, L (1984). Journal of Medical Science, 165, 250-276. FUTURE EVALUATIONS OF THE CCU
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27 WEDUl'JDE,
Issue 9 | November 2006
Herceptin: Is it really w o r t h it?
M o h a m m a d Zubair, Mohamed Abdi, Abdul Ghani Basith
C a n a d a ' s ailing healthcare system has been dealt another blow with the expensive and potentially lifesaving drug Herceptin®. The issues at stake question fundamental aspects of the Canadian healthcare system and raise ethical questions which have obvious answers but are difficult to implement. Herceptin® was approved in 1998 by the Food and Drug Administration and is being used on its o w n as a single agent or with conventional chemotherapy, specifically paclitaxel in treating HER2/neu-overexpression or HER2/ neu-positive metastatic breast cancer (MBC) (Willems, Gauger, Henrichs, & Harbeck, 2005).This article discusses the effectiveness and costs of Herceptin®. How DOES HERCEPTIN® WORK? In normal cells, the human epidermal growth factor receptor-2/neu (HER2/neu) protein functions in regulating cellular growth and division. The HER2/ neu protein is encoded by the cellular-erB-2 protooncogene (Bianco, 2004; Sahin, 2000). More specifically, the protein is a 185-kDa transmembrane tyrosine kinase receptor (Emens, 2005; Ross et al., 2004). Around 253 0 % of breast cancers are caused by an overexpression of the HER2/neu protein (FDA, 2005). Whereas a noncancerous breast cell would have two copies of the HER2/neu gene, the n u m b e r of HER2/neu gene copies is elevated in w o m e n with HER2/neu-positive breast cancer. This leads to a higher density of the HER2/neu protein on the cell surface, which causes increased cellular division forming a tumor. Unfortunately, being a more aggressive form of cancer with shorter survival rates, HER2/neu-positive breast cancer is associated with a poor prognosis (Altundag, Esteva, & Arun, 2005; Emens, 2005). Herceptin® is the brand n a m e for trastuzumab, which is a human-murine recombinant DNA-derived anti-HER2 monoclonal antibody (FDA, 2005). Herceptin® falls into the category of a biological therapy, since it is derived from living cells. Administered intravenously, it is used in targeted drug delivery for the treatment of HER2/neu-positive metastatic breast cancers (FDA, 2005; www.meducator.org
Yarden, Baselga, & Miles, 2004). Pharmacodiagnostic tools have shown that Herceptin® has a high affinity for the HER2/neu protein's extracellular domain (see Figure 1). Binding of Herceptin® inhibits further proliferation of HER2/neu-positive tumor cells by interfering with associated intracellular signals (FDA, 2005). The effects of Herceptin® m a y also be due to its ability to facilitate antibody-dependent cellular mediated cytotoxicity, which would involve the host's i m m u n e system (FDA, 2005). Herceptin® should only be administered once HER2/neu overexpression has been confirmed (Bilous et al., 2003). This can be diagnosed using either immunohistochemistry, which detects overexpression of the protein itself, or fluorescence in situ hybridization, which detects gene amplification (Willems et al., 2005; Ross et al., 2004). Herceptin® was identified using pharmacogenomics, which is the study of h o w an individual's genotype relates to that individual's response to a particular drug. More specifically, pharmacogenomics analyzes specific genetic alterations which, in the case of cancer, can be inherited from one generation of cancerous cells to the next (Bartlett, 2005). The overexpression of the HER2/neu protein or amplification of the HER2/neu gene is an example of a specific genetic alteration that transforms normal breast cells into cancerous ones (Yarden, Baselga, & Miles, 2004). ASSESSING THE EFFICACY OF HERCEPTIN® There are currently other breast cancer biological therapeutic drugs available on the market. Since Herceptin® is a relatively n e w treatment, it is important to report clinical trials that have assessed its efficacy. All patients involved in the Herceptin® clinical trials have been HER2/neu-overexpressing M B C patients. Clinical trials of Herceptin® have looked at, a m o n g other things, its effect on disease progression, the rate of death, and the reduced risk of death (Slamon et al., 2001; O'Shaughnessy, 2005). Until recently, traditional chemotherapy w a s the
Issue 9 | November 2006
^EDBLilBEl 28
Herceptin
Normal Cell
In normal breast tissue cells, the HER2 gene produces a protein receptor on the cell surface. These growth factor-like receptors are thought to play a role in normal cell growth by signaling the cell to divide and multiply.
HER2 Overexpressing Cancer Cell
Herceptin® (Trastuzumab)
It is thought that Herceptin (a Cancerous breast tissue cells that HER2 antibody) binds to numeroverexpress (or overproduce) the ous HER2 receptor sites found HER2 gene produce extra protein on the cell surface, blocking receptors on the cell surface. The the receptor sites and possibly higher density of receptors triggers preventing further growth by inthe cell to divide and multiply at an terrupting the growth signal. As accelerated rate, thus contributing a result, the HER2 antibody may to tumor growth. Approximately slow progression of the disease. 25-30% of all women with metastatic breast cancer overexpress the HER2 protein.
Figure 1: Comparing various HER2/NEU expression and Herceptin® binding (www.gene.com).
standard treatment for HER2/neu-overexpressing MBC. With the development of Herceptin®, however, this may change. Where chemotherapy has been used on its own to treat HER2/neu-overexpressing MBC, the results have not been very positive. Full treatment response rarely occurs and partial treatment response only occurs in 35 to 4 0 % of patients (Nahleh & Jazieh, 2005). On average the survival time can vary from 18 to 30 months with the latter corresponding to, in most cases, those who respond well to treatment (Nahleh & Jazieh, 2005). On the other hand, studies have demonstrated the efficacy of Herceptin® when it is used on its own. One study conducted out of the Vail d'Hebron University Hospital in Barcelona, Spain, showed a 19% overall response rate to Herceptin® on average (Ardavanis et al., 2005). In most of the current studies, Herceptin® is often administered in conjunction with chemotherapy to determine any improvements. It appears that in conjuction with chemotherapy, Herceptin® demonstrates synergistic anti-tumor activity that is greater than when used alone (Emens, 2005; Emens & Davidson, 2004; Adams & Weiner, 2005). According to a study published in The Indian Journal of Pediatrics, of traditional adriamycin or taxol based chemotherapy produced an average survival time of 20 months but
with the addition of Herceptin®, survival time increased to 29 months (Mohindru, 2005). Another study found that there was a higher survival period, 25.1 months, for patients that were administered both Herceptin® and chemotherapy, compared to survival of 20.3 months for patients only on traditional chemotherapy. The same study also showed that disease progression was delayed by an average of 3 months for those on Herceptin® and chemotherapy (Slamon et al., 2001). In a study conducted by the U.S. National Cancer Institute, there was a 5 2 % decrease in disease recurrence and a 3 3 % reduction in death with regard to patients on this combined method of treatment (U.S. National Institutes of Health, 2005). Although there seem to be many positive aspects of Herceptin, a common side effect in various studies has generated a lot of concern: the relative cardiotoxicity of the treatment. It has been shown that a combination of chemotherapy agents (specifically anthracycline and adriamycin) with Herceptin® lead to a 2 6 % increase in cardiotoxicity and congestive heart failure (Mohindru, 2005). Similarly, in another study, use cardiac dysfunction due to an increase of cardiotoxicity was the major drawback that appeared in experimental treatments (see Table 1). www.meducator.org
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Issue 9 | November 2006
British Columbia is the first province to establish funding formulae. The B.C. Cancer Agency and Ministry Fundamentally, the main concern with Herceptin® is the of Health set aside $8 million per year for breast cancer patients which began on July 2005 (BC Cancer Agency, associated cost. It costs more than $35,000 to treat one 2005). It is expected that about 160 w o m e n will benefit patient (Kinner, 2005). The steep price for this drug is a from the drug each year. Ontario has followed suit and result of the average $1.7 billion that is required to put the Ministry of Health and Long Term Care has provided n e w drugs on the market, according to the Bain report Herceptin® under a n e w provincial drug program released in 2005 (Gilbert & Rosenberg, 2004). To m a k e a facilitated by Cancer Care Ontario (Ontario Ministry return on the investment, drug companies must charge of Health, 2001). Quebec and Saskatchewan have also high market-based prices which lead to expensive been quick to follow, however, other provinces such treatments like Genentech's Herceptin®. As more drugs as Nova Scotia and Prince Edward Island pay for it on a are tailored for specific strains of cancer, higher costs case by case basis. should be expected. Reduction in costs would require S o m e health economics experts are questioning different economic principles, one in which drug the cost effectiveness of this cancer treatment. As a development would be less of a private enterprise and result, there are international trials which are currently more of a public service. evaluating effectiveness of the treatment in HER2/neuAlthough Herceptin® was approved for use by positive patients with primary breast cancer. Preliminary Health Canada in 1999, concrete national financing results are indicating treatment with this drug will schemes have yet to appear. Both the federal and lead to high initial cost but if less people progress to provincial governments have been hesitant because of metastatic breast cancer, resources can be saved on the current rising costs of prescription drugs and the advanced metastatic treatment which reduces total precedent that could be set. Instead, each province has health cost (Neyt, Albrecht, & Cocquyt, 2005). M been left to its o w n devices to c o m e up with a solution. O U R HEALTHCARE SYSTEM AND HERCEPTIN®
Treatment Used
Patients with Cardiotoxicity
Anthracycline and cyclophosphoamide Anthracycline, cyclophosphoamide, Herceptin® Paclitaxel and Herceptin® Paclitaxel
8% 27% 13% 1%
Table 1: Incidence of cardiotoxicity associated with various combinations of therapy for overexpressing HER2/neu M B C patients. Antracycline, adriamycin, cyclophosphoamide, and paclitaxel are all chemotherapeutic agents (Slamon et al., 2001).
LONG TERM OUTLOOK As more expensive cancer treatment drugs are introduced, health policy makers and politicians are wondering where to draw the line. Canadians are proud to have a healthcare system that ensures citizens d o not pay at the point of access. Legislation such as the Canada Health Act ensure this right is enjoyed across provinces, but if w e are to remain faithful to our healthcare roots, the nation needs to act quickly to c o m e up with financing schemes for costly emergent drugs. Robust financing schemes that produce equitable health outcomes are required before w e ask ourselves w h o will be allowed to live. This can only be achieved w h e n there is co-operation between research institutions, biopharmaceuticals, and government agencies. www.meducator.org
REFERENCES Adams, G.P. & Weiner, L.M. (2005). Monoclonal antibody therapy of cancer. Nature Biotechnology, 23, 114757. Altundag, K., Esteva, F.J, & Arun, B. (2005). Monoclonal antibody-based targeted therapy in breast cancer. Current Medicinal Chemistry - Anti-Cancer Agents, 5, 99-106. Ardavanis, A.,Tryfonopoulos, D., Orfanos, G., Karamouzis, M., Scorilas, A., Alexopoulos, A., & Rigatos, G. (2005). Safety and efficacy of trastuzumab every 3 weeks combined with cytotoxic chemotherapy in patients with HER2-positive recurrent breast cancer: findings from a case series. Onkologie, 28, 558-64. Bartlett, J.M. (2005). Pharmacodiagnosflc testing in
'MEDMUIOIl so breast cancer: focus on HER2 and trastuzumab therapy. American Journal of PharmacoGenomics, 5, 303-315. Baxevanis, C.N., Sotiropoulou, P.A., Sotiriadou, N.N., & Papamichail, M. (2004). Immunobiology of HER-2/neu oncoprotein and its potential application in cancer immunotherapy. Cancer Immunology, Immunotherapy, 53,166-75. BC Cancer Agency: Care and Research. (July 11, 2005). Breakthrough therapy to benefit breast cancer patients. Retrieved January 23, 2006, from http:// w w w . healthservices.gov.bc.ca/cpa/mediasite/pdf/ 2005HEALTH0008-000663.pdf. Bianco, A.R. (2004). Targeting c-erbB2 and other receptors of the c-erbB family: rationale and clinical applications. Journal of Chemotherapy, 16 (Suppl 4), 52-4. Bilous, M., Dowsett, M., Hanna, W., Isola, J., Lebeau, A., Moreno, A. Penault-Llorca, F., Ruschoff, J., Tomasic, G., &van deVijver, M. (2003). Current perspectives on HER2 testing: a review of national testing guidelines. Modern Pathology, 16, 173-82. Emens, L.A. (2005). Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. American Journal of Therapeutics, 12, 243-53. Emens, L.A., & Davidson, N.E. (2004). Trastuzumab in breast cancer. Oncology, 18,1117-28. Food and Drug Administration. (2005). Herceptin® Trastuzumab. Retrieved January 31,2005, from http:// www.fda.gov/medwatch/safety/2005/Herceptin_ Promo_PDF_Feb_2005.pdf. Gilbert, J., & Rosenberg, P. (April 19, 2004). There's N o SuchThing as a Free Drug. Retrieved January 29,2006, from http://www.bain.com/bainweb/Publications/ wbb_articles_detail.asp?id=16285&menu_url=wbb %5Farticles%2Easp. Health Canada. (1999). Biologic Products for H u m a n Use. Retrieved January 29, 2006, from http://www. hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/txt/ prodpharma/bio99et_e.txt. Her2+ Metastatic Breast Cancer Treatment. (2005). Retrieved January 12, 2005, from http://www. herceptin.com/herceptin/patient/index.jsp. Kinner, B. J. (July 25, 2005). D R U G COSTS: Insure Only the Neediest. Retrieved January 21, 2006, from http://www.fraserinstitute.ca/shared/readmore1. asp?sNav=ed&id=367. Mohindru, Verma. Engineered antibodies act as targeted therapies in cancer treatment. Indian J Pediatr 2005;72:943-947. Nahleh, Z.A., & Jazieh, A.R. (2005). Multitargeted therapy in estrogen receptor-positive, h u m a n
Issue 9 | November 2006 epidermal growth factor receptor-2-positive breast cancer. American Journal of Clinical Oncology, 28, 631 -633. Neyt, M., Albrecht, J., & Cocquyt. (2005). An economic evaluation of Herceptin® in adjuvant setting: the Breast Cancer International Research Group 006Trial. Annals of Oncology, http://annonc.oxfordjournals. org/cgi/reprint/mdjl 01 vl. Ontario Ministry of Health and Long Term Care. (March 3, 2001). Funding of Herceptin® for the treatment of breast cancer. Retrieved January 29, 2006, from http://www.health.gov.on.ca/english/providers/ pub/cancer/ann040301 .html. O'Shaughnessy, J. (2005). Extending Survival with Chemotherapy in Metastatic Breast Cancer. The Oncologist, 10 (supp 3), 20-29. Penny, M.A., & McHale, D. (2005). Pharmacogenomics and the drug discovery pipeline: w h e n should it be implemented? American Journal of PharmacoGenomics, 5, 53-62. Ross, J.S., Fletcher, J.A., Bloom, K.J., Linette, G.P., Stec, J., Symmans, W.F., Pusztai, L, & Hortobagyi, G.N. (2004). Targeted therapy in breast cancer: the HER-2/neu gene and protein. Molecular & Cellular Proteomics, 3, 379-98. Sahin, A.A. (2000). Biologic and clinical significance of HER-2/neu (cerbB-2) in breast cancer. Advances in Anatomic Pathology, 7,158-66. Slamon, D.J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., Baselga, J., & Norton, L (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N e w England Journal of Medicine, 344, 78392. U.S. National Institutes of Health. National Cancer Institute. (April 25, 2005). Herceptin® Combined with Chemotherapy Improves Disease-Free Survival for Patients with Early-Stage Breast Cancer. Retrieved March 17, 2006, from http://www.cancer.gov/ newscenter/pressreleases/HerceptinCombination20 05. U.S. National Institutes of Health. National Cancer Institute. (December 24, 2004). Trastuzumab (Herceptin®) Effective in Early Breast Cancer. Retrieved March 17, 2006, from http://www.cancer. gov/clinicaltrials/results/herceptin1005. Willems, A., Gauger, K., Henrichs, C , & Harbeck, N. (2005). Antibody therapy for breast cancer. Anticancer Research, 25,1483-9. Yarden, Y, Baselga, J., & Miles D. (2004). Molecular approach to breast cancer treatment. Seminars in Oncology, 31,6-13.
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Issue 9 | N o v e m b e r 2006
31 *MEDUL'M
MedQuiz Have you read all the articles? Test yourself and see h o w well you understood the articles by answering the questions below.
c) A low rate of keratin formation in the skin's outer layer contributes to acne formation d) Most research suggests that hormonal agents are about as effective as oral antibiotics
1. What are the four criteria for cardiac care? I. the ability of trained nurses to initiate resuscitation 4. The following sentence has the format "Statement 1 II. continuous electrocardiographic monitoring B E C A U S E Statement 2". III. admission of patients with A M I to a single specialized unit of the hospital Decide whether statement 1 is true, whether statement 2 is IV. cardiopulmonary resuscitation with external ventricular true, and whether the R E A S O N I N G (the'because'relationship) defibrillation between them is valid. a) I, II b) I, III, IV c) I, II, IV d) All of them
Statement 7: "Changes in personality such as depression are considered hallmark characteristics of the disease"; BECAUSE Statement 2: "They s h o w up in the latter stages of Alzheimer's."
2. Which of the following is not a complication caused by DiGeorge S y n d r o m e ? a) Craniofacial Anomalies b) Thymus Gland Abnormalities c) Heart Defects d) Hyperparathyroidism
a) Statement 1 and Statement 2 are both correct, and the reasoning is valid. b) Statement 1 and Statement 2 are both correct, but the reasoning is N O T valid. c) Statement 1 is correct, but Statement 2 is N O T correct. d) Statement 1 is N O T correct, but Statement 2 is correct.
3. Which of the following statements regarding acne are false? a) S o m e treatments for acne can cause severe birth defects, including brain and cardiac defects b) The link between Accutane and depression is often disputed
5. A c o m m o n side effect of Herceptin use is: a) Liver impairment b) Congestive heart failure c) Collapsed Lungs d) Decline of the i m m u n e system q s 'Dfr '3ÂŁ 'PZ 'PI :si3MSu\/
Back Row (Left to Right): Alexandra Perri, Harman Chaudhry, Fify Soeyonggo, Amandeep Rai, Crystal Chung, Stephanie Low, Ran Ran Middle Row (Left to Right): Navpreet Rana, Jacqueline Ho, Siddhi Mathur, Sarah Mullen, Jeannette So Front Row (Left to Right): Jonathan Liu, Tyler Law Absent: Harjot Atwal, Shama Sud
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