E - Learning in Medical Education
Posted by on Thursday, 11th August 2011
There is a growing debate in this knowledge hungry society that doctors have not updated themselves with recent trends and newer developments in medicine. There is some truth in their concern. The growing number of medical schools and the equally large number of quacks have not helped in improving the health care in our country. The goal of this article is to introduce many of the aspects of e-Learning as it pertains to medical education.
Traditionally, medical education had as its foundation a combination of didactic instruction in the classroom and integrated, hands-on "Socratic Method" learning in the clinical setting. Of late, there has been an increase in the use of problem-based learning discussions (PBLD's) in an effort to integrate basic science knowledge and clinical decision making with a goal of teaching critical decision making skills to upcoming physicians and other health care providers. Most Medical schools these days are realizing the importance of incorporating newer modalities of teaching. In countries where the patient outflow is poor for students learning simulation techniques are of increasing usage.
Medical education, especially in the advances stages of training, has many unique problems such as the temporal and geographic distribution of students, residents, and the physician instructors. Further complications result from unpredictable schedules that are present in most areas of medicine leading to poorly attended or cancelled lectures. Learning is the sharing or transfer of information between two parties. It is the phasing dispensation of knowledge from people of integrity and higher learning with zeal of transforming their realized knowledge to deserving souls who have similar intentions of propagating the sacred knowledge. Of course the definition of knowledge changes with increasing tends of materialism as seen by mushrooming of various so called temples of learning .Over the course of time, many modalities and theories about learning have been elucidated with varying degrees of effectiveness. With an increasing prevalence of computers in and out of the classroom and the development of more sophisticated web-based tools, knowledge transfer is increasing going high-tech. Similar to prior methods of teaching and learning, computer-based, e-Learning, has its own set of problems and potential. Medical education, especially in the advances stages of training, has many unique problems such as the temporal and geographic distribution of students, residents, and the physician instructors. Further complications result from unpredictable schedules that are present in most areas of medicine leading to poorly attended or cancelled lectures. E-learning adds many dimensions to the educational process and if utilized well, has the potential to enhance both the students and instructors educational experience. One of the problems with traditional didactic lectures is that they often present information that targets one of the many learning style of the students involved. In addition, the time and resources required to deliver the material is high and often does not completely meet the needs of those who are participating. One benefit of e-learning allows students to access the lectures and other material when they are most attentive. In addition, students have the ability to review the material to the degree they feel necessary. It is my hope this article touches the surface of some of the current web tools available for use in the area of education. Many of these tools are nonspecific and can be integrated well into medical education. Blogs, short for web logs, are also easy to update and maintain web pages with a layout that resembles a journal. Students and instructors can utilize these web resources to discuss topics and concepts. In addition to journaling, others can interact with the material and leave comments. For those that are interested, many sites have been set up to host these web resources and are very easy to manage, even for those who have relatively minimal computer sophistication.
Today, Continuous Medical Education (CME) becomes a crucial factor, because the life of knowledge and human skills in the field of medicine is shorter than ever. That causes the increasing pressure to remain at the forefront of medical education throughout doctors’ career. E-learning comes with solutions and methods, which can be very helpful in supporting doctors with access to the up-to-date medical knowledge and achievements. It allows creation of interactive model of learning, which stimulates knowledge acquisition. Another advantage is that e-learning provides flexibility in both time and location, while accessing medical curriculum presented online. There is a possibility of collaboration between teachers and students from different universities, which allows exchange of knowledge and experiences.
Implementation of e-learning methods in medical education is needed to provide students with new ways of gaining knowledge. However certain steps must be taken to choose the solution, which is the best for the given learning area. To keep up to date with the latest scientific breakthroughs, current medical debates and state-of-the-art medical technology you don’t need to go on expensive further training seminars far away from your workplace. The only thing you need is a computer with online access – and the right links to e-learning (electronic learning) websites. These online resources offer a vast amount of possibilities in different medical fields tailor-made for a variety of users: Students can use it as well as trained physicians, employee workers or managers. Across the world many companies, universities and institutions maintain Virtual Academies. The providers strive for certification and international acknowledgment of this type of education.
We are just beginning to harness the power of the internet for the delivery and management of medical education. Even without a clear demonstration that e-learning is superior to traditional lectures; the use of online learning provides solutions that can overcome some problems with traditional education, especially in the area of medicine. With increasing constraints being placed on medical educators, one needs to explore other avenues for effective knowledge transfer to trainees in health care. The harnessing of computer technology, more specifically web-based tools open the door for collaboration amongst both students and teachers. One platform that harnesses the ability to deliver knowledge to students as well as collect information about the helpfulness of this information is the web-based Moodle e-learning platform.
Prof G S Patnaik is a consultant orthopedic and Trauma surgeon based in Bhubaneshwar.
Rate It
Emergency Department staffing
Posted by on Wednesday, 5th January 2011
The Emergency Department (ED), sometimes termed Accident & Emergency (A&E), Emergency Room (ER), Emergency Ward (EW), or Casualty Department is a hospital or primary care department that provides initial treatment to patients with a broad spectrum of illnesses and injuries, some of which may be life-threatening and require immediate attention. In some countries, Emergency Departments have become important entry points for those without other means of access to medical care. Staff teams treat emergency patients and provide support to family members. The emergency departments of most hospitals operate around the clock, although staffing levels attempt to mirror patient volume, which in most ED's finds its nadir between 2:00 am and 6:00 am. Most patients seek the Emergency Department in the afternoon and evening hours, and staffing mirrors this phenomenon.
The vast array of people caring for patients in an emergency department can be quite confusing to the average health care consumer -- as confusing.
Additionally, most people are uncertain of the training and background necessary to become a member of the emergency-department team. Well, here's the scorecard.
Emergency Physician
Physician who specializes in the care of patients with acute injuries or with diseases that are an immediate threat to life or limb. A "board certified" specialist in emergency medicine is an emergency physician who has achieved certification by the American Board of Emergency Medicine (if an MD) or the American Osteopathic Board of Emergency Medicine
Emergency Nurse.
Nurses care for patients in the emergency or critical phase of their illness or injury. A specialist nurse who will independently assess, diagnose, investigate, and treat a wide range of common accidents and injuries working autonomously without reference to medical staff. They primarily treat a wide range of musculoskeletal problems, skin problems and minor illness, many are considered experts in wound management. They are trained in advanced nursing skills which though medical in nature - such as taking a full medical history and examination, x-ray interpretation, prescribing, suturing, & plastering, also encompass a holistic assessment of the patients needs, taking into account the need for health teaching and education, continuing care within the family and ongoing health support in the community.
PhysicianAssistant
Many emergency departments utilize physician assistants (PA). PAs work under the supervision of an emergency physician. They can examine, diagnose and treat patients (usually the less complicated ones) and review their findings with the physician.
EmergencyDepartmentTechnician
The tasks that performed may include taking your vital signs, drawing your blood, starting your IV, performing EKGs, transporting you to and from various tests, and providing aid and comfort to family and friends.
UnitSecretary
This essential member of the team is one you don't hear about very often. He/she often handles the communication needs of the ER. A few important examples of important communication needs include the emergency physician needing to speak to the patient's family physician, families calling about their loved ones, family physicians needing to inform the emergency department about patients being sent in, or patients calling in needing medical advice. Also, he/she coordinates the ordering of diagnostic tests.
Physicianintraining
An attending physician who usually has extensive experience in emergency medicine supervises these physicians. There are ways to bridge the nursing productivity gap, while improving staffing processes, improving efficiency, and creating a vision for the future. To improve staffing processes one has to increase forecasting accuracy, match staffing to demand, increase management vigilance, smooth the workload variation and enhance nurse efficiency in the emergency room.
In the hospital industry cost information plays a critical role in maintaining a competitive advantage. Strategic cost management allows us to provide low cost care. For example, reducing the cost of providing care by improving a process would allow the organization to reduce the cost to the patient, thus reducing customer sacrifice.
Managers will be forced to determine which activities are important if customer value is emphasized. The healthcare industry requires that managers be familiar with many functions of the financial end of business. Nurses have often looked the other way when it comes to finances and continually focused on patient care. In the year 2001 the attitudes and focus must shift to keeping the healthcare facility viable in the business world. Relating patient care, hours worked, and the number of nurses required to provide low cost, quality care is of extreme importance in today’s environment. This broader vision allows managers to increase quality, reduce the time required to service customers (both internal and external), and improve efficiency. Continuous improvement is fundamental for establishing a state of healthcare excellence.
Next-day productivity profiling holds each manager accountable for the outcome of his or her specific area and to manage his or her resources appropriately. Imprecise staffing standards and infrequent monitoring hinders flexing of staff and leaves managers unaccountable for productivity. The emergency department will be profiled daily on performance against productivity targets. They will use productivity standards and daily volumes to determine real-time, the amount of staff needed to meet the demand. In most cases, the core staff will already be in place, and only upward adjustments will prove necessary. Managers are being trained to look at the business, and to be able to forecast the needs of the units and react to the needs efficiently. It is the expectation that this process will become routine, requiring moderate effort to maintain.
To improve emergency department staffing a master schedule of worked hours is reviewed daily to determine the daily census and volume and the per shift census and volume. Then the total worked hours scheduled is evaluated along with the worked hours per shift per unit. Managers are actually evaluating labor on a shift-to shift basis. Real-time reporting of adherence to customized productivity standards enables more accurate matching of staffing to demand. This process prevents hiring unnecessary personnel and fosters a permanent focus on staff efficiency and cost control.
Study also shows that that between the hours of one am and ten am, historically the census is low and requires less staffing. The emergency department survey also reflected that the peak volume times in the emergency department were from 10am to 12 midnight and this has provided needed information on start times and these surveys were utilized in formulating the schedule. It is essential to obtain staff buy-in to effectively implement this process in any organization.
Implementation of the Emergency Department Productivity Profiling System will reduce the number of FTE'’ needed per shift. This will further reduce cost associated with labor, as staff will be utilized more efficiently during peak arrival times. Thus, allowing to accurately plan for core and flexible staffing needs. Managers will be held accountable to department-specific hours-per-unit targets for flexible staffing. In turn, managers will be provided with timely, structured feedback on their performance against these targets. The staffing matrix developed for the Emergency Department will be adjusted periodically to further improve performance and reflect process or technology changes should they be needed.
References
Alba, T. (2000). Next-Day Productivity Profiling. Healthcare Advisory Board (Ed.), Nursing Cost Advantage, (Volume III, pp. 43-49). Washington, D.C.: The Advisory Board Company.
Ansari, S. (2000, March). Activity Based Management. Retrieved June 19, 2001 from the World Wide Web: http://www.wku.edu/~aldricr/.
Bellandi, D., Kirchheimer, B., & Galloro, V. (2001). Overall, not so bad. Modern Healthcare, Volume 31, pp. 36-37.
Coates, K. (2001, June). Trickle-down Effect. Nurse Week, Volume 6, p.13.
Covey, S. (1991). Managing Expectations. In Covey, S. (Ed.), Principle-Centered Leadership (pp. 204-205). New York, New York: Franklin Covey Co..
Hansen, D., & Mowen, M. (2000). Current Focus of Management Accounting. In Sears, M. (Ed.), Management Accounting (5th ed., pp. 10-15). Cincinnati, Ohio: South-Western College Publishing.
Nelson, D., & Quick, J. (2000). Forces for Change in Organizations. In J. Szilagyi (Ed.), Organizational Behavior (Third ed., p. 602). Cincinnati, Ohio: South-Western College Publishing.
Parker, C. (2001, June 11). AHA report shows staffing shortages threaten access to quality health care. AHA News, pp. 1, 2.
Pearson, C., & Barton, L. (2001). Vacancy Review Council. The Healthcare Advisory Board (Ed.), Liberating Hospital Economics, Volume I, pp. 37-43). Washington, D.C.: The Advisory Board Company.
Shaffer, F. (2001). On the Front Lines: A scan of the organizations that influence practice. Curtain Calls, Volume 3, p. 3.
Solovy, A. (2001). Mission Makes Wall Street. Hospitals & Health Networks, Volume 75, p. 38.
Category (
Trauma) |
Views ( 15239 ) | User Rating
Rate It
ORTHOPAEDIC MATTRESSES
Posted by on Wednesday, 5th January 2011
ORTHOPAEDIC MATTRESSES
In one episode of Merlin series whereby the Prince Arthur wanted to act like a normal citizen, whereby he stayed in his servant’s house. There was no double bed, only the bed for the servant. The prince has to sleep on the floor, but asked his another servant to get him his mattress from the palace. Why do you think a mattress is so important to him? It’s simple, because he do not want to get backache.
Nowadays, most of the people sleep on the bed or mattress, but why still many people suffer from backache? Maybe the mattresses they used are not good? How do you know that mattresses you are sleeping on are good enough? Just ask yourself how relaxed, rested or rejuvenated you feel immediately after you get up first thing in the morning? If the answer is not very, maybe it’s time to get a new mattress or change to orthopaedic mattress.
Why so many people suffer from back pain? There are of course many different answers to this question, but the quality of bed and mattress play a big role in this problem. Most people buy low quality mattress and kept them for too long. This bed already offer poor support and quickly goes off by time. Therefore they fail to provide support that the back need. This will avoided by orthopaedic mattresses.
The spine, along with the muscles and ligaments that enable it to work, can be easily aggravated, but the good news is that the back is also very robust and flexible and has great powers of recovery. This means that most back related problems can be rectified and that includes those caused by poor mattress support.
Do you wonder how mattresses can provide support to the back? The natural shape of the spine is double S. This shape needs to be maintained to keep the health of the back and ultimately the whole body. When this spine is not supported, the problem with back will arise.
In most of the people, the spine is poorly design structure which involve in many activities such as rotating and bending. During sleep, usually the spine get the opportunity to rest and recover. This is of course can be accomplish by a good and comfortable mattress which is designed as such to support the spine, skeletal structure and the muscles.
Nobody should use his mattress more than 10 years. This is because all mattresses that are 15-29 years old will be unable to provide an adequate support and will bring down the quality of the sleep ultimately to the health. However, the mattress does not need to be old to be changed. If you ever feel uncomfortable, achy and tense after waking up, It could be the sign to change the mattresses.
Unsuitable mattress usually manifest as minor aches or discomfort. Over time, it may progress into severe to the point that it irritates the daily activities. If the source of problem is not removed, the person has to suffer the pain forever. It is advisable to prevent the problem than to cure the disease. In order to prevent all this, orthopaedic mattress is highly suggested.
Orthopaedic mattress is a mattress is design as such to provide support to the double S shaped human spine. In a recent studies that tested mattress ergonomics, 12 women were the subjects were tested by lying on an incompressible wooden surface was compared with various mattresses. All of the mattresses were judged as significantly more comfortable that the wooden surface, but there were no differences between the mattresses type, even these included orthopaedic mattress. Measure of shoulder, elbow, hip, knee, body ankle pressures showed few significant differences and surprisingly, there were no significant associations between measures and comfort ratings.
However, how hard or soft the mattress feels is thought to be an important factor in reducing or preventing back pain. Comparison of sleeping on a futon or softer air mattress showed that sleep onset latency, waking after sleep onset and the sleep efficiency index were comparable for both mattress, but subjective sleep evaluation tended to be offer for air mattress. A study of sleep quality and bed firmness showed that 4 of 9 male subjects slept significantly better on the softer mattresses, while 2 slept better on the harder mattresses. The greatest difference in quality occurred when changing from the subject’s own mattress to one of the test mattresses, and the authors concluded that it may take several days to adapt to a new sleep surface. This is may be why business travelers often report sleep difficulties.
The Cornell University’s Ergonomics group suggests that if you are to look for a mattress, then here is the guidelines:
- Designed to conform to the spine’s natural curves and to keep the spine in alignment when you lay down
- Designed to distribute pressure evenly across the body to help circulation, decrease body movement and enhance sleep quality
- Designed to minimize the transfer of movement from one sleeping partner to the other.
- Design with perimeter edge support
The orthopaedic mattresses are of course fulfill all the guidelines above as they are designed as such to provide support to spine, skeletal structures and muscles. There are few types of this mattress which are designed differently in their structure and how they function.
There are 2 basic type of orthopaedic bed, a divan bed and bed constructed with a frame. A divan bed has under bed storage with draws or compartments and the mattress is supported by a sprung or platform topbase. These bed are therefore consider as multipurpose.
In the other hand, orthopaedic bed comprising of frame, can be constructed from any number of materials including timber and steel. There is no separate storage and can neither have a void beneath them or sit closer to the floor than a divan. These beds can also be made in such a way to be adjustable through the addition of electric motor and a remote control unit.
The mattresses are further classified according to their support and springing system. They are achieved either through one or a combination of different systems. They primary spring and support methods used today are “spring systems”, memory foam, latex foam and air cushioning.
Within the category of spring system, there are 3 slightly different construction approaches which are “posture spring” (Slumberland, Silentnight and Sealy), “open coil” (Airsprung, Silentnight and Sealy) and “pocket sprung”
Posture spring are made from a continuous single wire which enables all the spring to be interlinked. This creates support system that allow every spring to act together with other spring.
Open coils bed have a frame of springs that are linked together by further horizontal or vertical coils to create a tight and interconnected mesh of springs. They are very firm and been regarded for their orthopaedic qualities.
Pocket sprung have individual springs that are placed in separate pockets which run in rows along and across the mattress.
Memory foam beds able to contour themselves to unique shape of anyone who sleeps on them and offer superior support by balancing out weight distribution across the body. The ability to give orthopedic characteristic made them highly popular.
Latex foam beds is fairly new, but offers many advantage of memory foam and the natural rather than synthetic latexes have the additional advantage of sleeping cool, hypoallergenic and no noticeable odor.
There is also a type called gel bed which is relatively new innovation. Contrary to the name, it is not a viscous liquid like material, rather something that resembles rubber and it is usually manufactured in a nest or honeycomb with large air voids between the small sections. The benefits of gel bed is that it is multi fold and offer same characteristic as memory and latex foam.
An air mattress is an inflatable mattress that is typically made of plastic, textile reinforced plastic or rubber. The support is achieved by means of filling the mattress with compressed air. Therefore, it can be easily stored and transported, so suitable for camping of travelling.
As mention earlier, the orthopedic mattresses are solely to provide support to the spine especially in elderly and those who work hard in the day and need good sleep at night. As more and more people suffering from back pain, so this mattress is recommended for all.
It is the lifeline to heath of spine and back as it is benefit body as a whole by providing supportive and restful sleep so that we recover from busy activities day to day. It helps to avoid stiffness, aches, muscular discomfort and back pain by allowing the back to retain its natural position without the build of unnecessary tension or pressures.
However, there is also an advantage of this mattress that it is rigid attachment of big diameter springs , therefore it reduce the orthopedic properties of the mattress.
ORTHOPEDIC CHAIR
As with the mattress, the orthopedic chairs are also design as such to support the body and the back thus promote a good and comfortable sitting posture. They have different designs to suit the activities done using it. Such as, one chair is suitable for rest and the other suitable for office job.
Usually the orthopedic or also known as ‘ergonomic’ chairs are design to suit 2 conditions – home and office.
At home of course is the place to run away from a hectic life outside. Sitting on the orthopedic chair can provide relaxation by providing massage and or vibratory motion or even heat from controllable embedded heat pads.
In an office environment, orthopedic chair function primarily to attain good posture while using the office equipment, such as computers. It takes account for users who need to use have free and unrestricted hand movement, at the same time with good back support.
There are three main categories of orthopedic chair – support chair, lift chair or ‘rise and recline’ and massage chair. All three of them have their particular function but still share same characteristic to make the user comfortable. And it is possible to combine all the three function in one chair.
The support chair is designed to make sure that your spine is in the possible best condition when you are sitting down. As mention before, spine is double S profile, in the same boat with the orthopedic mattress to provide comfortable to the back and to prevent back ache. This chair also minimize the chances of your position to slip away.
The lift chair helps to user to make transition from a seated position to a standing posture easy in some less-able members in the community. This involves an automated system built into the chair itself, as it lift and tilts to help them get up or even help them to get into the chair. Elderly man, injured or those with back issues can make use out of this characters.
While massage chair, as the name depict, it gives pleasure by providing vibratory, mechanical air or water muscle stimulation. Originally, it was used as medical aid, but nowadays it is more to luxury item.
In office environment, especially if the job need you to focus to the equipment for entire day, so it is easy to get weary. Maybe quite some time needed to restore the energy back, so kind of time wasting going on in the office. It looks simple, but productivity tends to slide if people are distressed or if they got sore due to bad posture, I recommended that employers should purchase this chair so the employees remain healthy.
These chair usually don’t have many accessories attached to them, the important thing is the worker’s hand are free while their back are taken care of. Due to different atmosphere between home and office, the office chair tend to have more Spartan design philosophy and more focus on support than decorating and the most common options are height and tilt adjustment, so it can be considered part of a comfortable and productive working environment.
Of course, none of this chair works if people don’t know how to sit properly. The bottom part of your back should be in contact with the chair’s back, that is the proper technique of sitting. For those who could not afford the expensive orthopedic chair, a lumbar pillow or spine support can be put on the chair, but the result is not as good as the chair itself.
Rate It
STEM CELL TRANPLANT IN SPINAL CORD INJURY
Posted by on Wednesday, 5th January 2011
INTRODUCTION
Stem cell research is advancing knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. This promising area of science is also leading scientists to investigate the possibility of cell-based therapies to treat disease, which is often referred to as regenerative or reparative medicine.
WHAT ARE STEM CELLS?
Stem cells are cells found in most multi-cellular organisms. They have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that renew themselves for long periods through mitotic cell division and differentiation. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.
The two broad types of mammalian stem cells are: embryonic stem cells that are isolated from the inner cell mass of blastocysts, and adult stem cells that are found in adult tissues.
Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, stem cells in developing tissues give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells and progenitor cells act as repair system for the body, replenishing specialized cells, but also maintaining the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.
Stem cells can now be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture.
Highly plastic adult stem cells from a variety of sources, including umbilical cord blood and bone marrow, are routinely used in medical therapies. Embryonic cell lines and autologous embryonic stem cells generated through therapeutic cloning have also been proposed as promising candidates for future therapies.[3
UNIQUE PROPERTIES OF STEM CELLS
Stem cells differ from other kinds of cells in the body and regardless of their origin have three general properties. They are capable of dividing and renewing themselves for long periods; they are unspecialized; and can give rise to specialized cell types.
Stem cells do not have any tissue-specific structures that allow it to perform specialized functions. A stem cell cannot work with its neighbours to pump blood through the body (like a heart muscle cell); it cannot carry molecules of oxygen through the bloodstream (like a red blood cell), nor can it fire electrochemical signals to other cells that allow the body to move or speak (like a nerve cell), but, more importantly, it can give rise to the development of these specialized cells by a process known as differentiation.
The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA, and carry coded instructions for all the structures and functions of a cell. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighbouring cells, and certain molecules in the microenvironment.
Unlike the above mentioned specialized cells, stem cells are capable of proliferating for long periods. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.
Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to the many types of blood cells such as red blood cells, white blood cells and platelets. Until recently, it had been thought that a haematopoietic stem cell in the bone marrow could not give rise to the cells of a very different tissue, such as nerve cells in the brain. However, a number of experiments over the last several years have raised the possibility that stem cells from one tissue may be able to give rise to cell types of a completely different tissue, a phenomenon known as plasticity. Examples of such plasticity include blood cells becoming neurons, liver cells that can be made to produce insulin and haematopoietic stem cells that can develop into heart muscle.
HISTORY OF STEM CELL RESEARCH
• 1908 - The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874–1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.
• 1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; like André Gernez, their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
• 1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
• 1968 - Bone marrow transplant between two siblings successfully treats SCID.
• 1978 - Haematopoietic stem cells are discovered in human cord blood.
• 1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
• 1992 - Neural stem cells are cultured in vitro as neurospheres.
• 1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
• 1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin–Madison.[60]
• 2000s - Several reports of adult stem cell plasticity are published.
• 2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[61]
• 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[62]
• 2004–2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
• 2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
• 2005 - Researchers at UC Irvine's Reeve-Irvine Research Center are able to partially restore the ability of mice with paralyzed spines to walk through the injection of human neural stem cells.
• August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka.[63]
• October 2006 - Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.[64][65]
• January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[66] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[67]
• June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[68] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[69]
• October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[70]
• November 2007 - Human induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of pluripotent stem cells from adult human fibroblasts by defined factors",[71] and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced pluripotent stem cell lines derived from human somatic cells":[72] pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
• January 2008 - Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo[73]
• January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[74]
• February 2008 - Generation of pluripotent stem cells from adult mouse liver and stomach: these iPS cells seem to be more similar to embryonic stem cells than the previous developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques.[75]
• March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by clinicians from Regenerative Sciences[76]
• October 2008 - Sabine Conrad and colleagues at Tübingen, Germany generate pluripotent stem cells from spermatogonial cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation.[77]
• 30 October 2008 - Embryonic-like stem cells from a single human hair.[78]
• 1 March 2009 - Andras Nagy, Keisuke Kaji, et al. discover a way to produce embryonic-like stem cells from normal adult cells by using a novel "wrapping" procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change.[79][80][81] The use of electroporation is said to allow for the temporary insertion of genes into the cell.[82][83][84][85]
• 28 May 2009 Kim et al. announced that they had devised a way to manipulate skin cells to create patient specific "induced pluripotent stem cells" (iPS), claiming it to be the 'ultimate stem cell solution'.[86]
DEVELOPMENT OF STEM CELL RESEARCH
The spinal cord needs more protection then any other organ or system because unlike other organs, the spinal cord once damaged, cannot regenerate. While the majority of cells found in the central nervous system are born during the embryonic and early postnatal period, scientists recently discovered that new neurons are continuously added to two specific regions of the adult mammalian brain (Reynolds and Weiss 1992). Neural stem cells were isolated from the dentate gyrus of the hippocampus and the walls of the ventricular system called the ependymal layer. The progeny of these stem cells differentiate in the granule cell layer, meaning neurogenesis continues late into adult rodent life. These stem cells also migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into neurons and glial cells (Luskin, 1993). Nerve cell differentiation has been witnessed in vivo, as well as in vitro when stimulated with an epidermal growth factor (Gage, 1995).
Along with pluripotent stem cells progenitor cells, a more restricted type of stem cells, are found in the hippocampus and ependymal layer. These cells are immature cells that are predetermined to differentiate into neurons, oligodendrocytes, and astrocytes. In 1995 Frissen observed that the presence of nestin increases in response to spinal cord injury. Nestin is a protein expressed by stem cells: presence of it indicates neural stem cells are much more active then previously believed. Our brain naturally increases the production of stem cells to aid an injured CNS. In 1999, Johansson and Momma observed that the only active progenitor cells were differentiating into astrocytes. They labeled ependymal cells with a Dil injection so migration could be followed. After making lesions in the spinal cord they waited four weeks and then observed the progress of the ependymal cells. They tested the cells found in the scar tissue around the site of injury and found that all DIL marked cells were astrocytes. This indicates that the progeny from ependymal cells had only differentiated to astrocytes. Stem cells do respond to spinal cord injury, just not for the purpose of reestablishing connection between neurons.
This realization sparked scientist’s interest in understanding what triggers these progenitor cells to proliferate. Scientists began to focus on neurotrophic factors that triggered this differentiation, specifically the presence of brain derived neurotrophic factors (BDNF) and neurotrophin 3 and 4 (NT-3 and NT-4). In the early 90’s these trophic factors were targeted as what triggered axon growth during early development. NT-3 also is expressed in greater amounts in response to spinal cord injury. In 1994 Schwab reported dramatic increase in function, and regrowth of a partially severed cord of rats after treatment with NT-3. In 1997 Grill, Gage, and colleagues published a paper examining the effects of transplanted NT-3 on motor skills and morphology after induced spinal injury in mice. They focused on the corticospinal tract, the pathway in charge of making voluntary movements. NT-3 has been previously observed to promote regrowth of corticospinal axons, and preserves degenerating motor neurons.
Grill and colleagues induced lesions in the dorsal hemisection of adult rat’s spinal cord, resulting in severely limited motor ability. Next grafts of syngenic fibroblasts, genetically altered to produce NT-3, were transplanted into the lesion cavity of the experimental group. These rats were kept alive for three months and put though a series of tests to monitor motor improvement. These tests examined coordination, ability to walk on inclined surfaces and precision of foot placement. After three months these rats were killed for the purpose of a quantitative cell count.
Recipients of the NT-3 secreting grafts showed significant improvement in motor skills over the control group, although they did not recover to the full ability they had before injury. After three months recipients of the NT-3 grafts demonstrated growth of corticospinal axons up to 8 mm from where the stem cells were transplanted. Only the injured axons at the lesion site showed any sign of regrowth. Uninjured axons showed no effort to reestablish connections across the site of injury. This suggests that NT-3 only responds when corticospinal axons are injured. If scientists could pinpoint signals triggering this response there is potential to manipulate the process in a manner causing neural cells to differentiate.
Triggering neurotrophic factors in hopes of inducing progenitors to proliferate is one of two major areas of study in spinal cord regeneration. Scientists also can derive undifferentiated embryonic stem cells (ES cells) from foetal spinal cord tissue and then mature them into cells that are suitable to implant into the damaged spinal cord. When using ES cells, researchers have two options: they can treat ES cells, allowing them to mature into CNS cells in vitro before transplantation, or they can directly implant differentiated cells and depend on signals from the brain mature the cells. This technique became possible when Reynolds and Weiss found that stem cells taken from the brain could be propagated in vitro. This allowed labs to duplicate what occurs naturally in the brain, and attempt to use the product to re-grow the damaged cells.
In December of 1999 McDonald and colleagues from Washington University School of medicine successfully implanted ES cells in laboratory rats. McDonald induced thoracic spinal cord injury in rats using a metal rod 2.5 mm in diameter resulting in paralysis. Nine days after the injury McDonald and colleagues transplanted roughly 1 million ES embryoid bodies pre-treated with retinoic acid into the syrinx that had formed around the contusion. During the nine days that passed between injury and transplantation, all the standard events following a spinal cord injury occurred. At the time of injury some cells died immediately, followed by a second wave of apoptosis within the first 24 hours. The centre of the bruised spine filled with fluid becoming a cyst referred to as syrinx. McDonald injected the ES cells into this cavity.
Two weeks after the transplantation ES stem cells filled the area normally occupied by glial scarring. After five weeks the stem cells had migrated further away from the implantation site. Although a number of them had died, there was still enough for the rats to have a growing supply of neurons and glial cells. Most of the surviving cells were oligodendrocytes and astrocytes, but some neurons were found in the middle of the cord. The rats regained limited use of their legs. Paralysis had been cured!!
McDonalds work in 1999 represented new successes in stem cell technology but this technology is yet to be tested in humans. A major obstacle remains: although scientists are achieving results, they don’t understand the factors responsible for what occurs. In McDonalds study, the regaining of functions could result from the few differentiated neurons. Another possibility could be that the high differentiation of oligodendrocytes re-myelinated enough axons to reestablish communication. Or perhaps functions regained due to ES cells producing growth factors—more research will have to be done before these options are narrowed down. Additional to unclear understanding of the process, other complications exist. Any introduction of foreign cells into the body triggers the immune system. ES cells would not simply be accepted into the host CNS. McDonald used cyclosporine to prevent rejection in the rats, but things get more complicated when testing begins on humans. The brain and spinal cord is complex, mysterious realms of the body—until science can predict the exact affect of evolving technologies, no testing on humans can occur.
A major motivation behind spinal cord research has been Christopher Reeve. Injured in a horseback riding incident, Christopher Reeve suffered a cervical spinal cord injury that left him quadriplegic. Christopher Reeve began the Christopher Reeve Paralysis Foundation (CRPF). CPRF funds research to treat or cure paralysis resulting from spinal cord injury or other CNS disorders. CPRF supports a Research Consortium, which collaborates the work of nine laboratories, as well as funds an international individual grants program. Several of the labs involved in the Research consortium focus on stem cells, making a lot of progress. The Salk Institute, run by Dr. Fred Gage examines the progenitor cells differentiating into glial cells. Someday they hope to manipulate these progenitor cells, inducing differentiation into neural cells.
STEM CELL TRANSPLANT VS ETHICS
There are a lot of people who find stem cell research extremely unethical. Scientists have found the most success with ES cells taken from embryoid spinal cords: although the ES cells are taken from embryos consisting at most of 64 cells, they still have potential to develop into a human being. People who believe life begins at conception remain morally against stem cell research. Justification is that the stem cells are derived from embryos discarded from fertility clinics. These embryos would be wasted if not used for stem cell research. Christopher Reeve published a position paper in response to the moral concerns and President Bush's decisions on stem cell researching. CPRF supports responsible stem cell research, recognizing the fine ethical boundaries existing in this technology.
TRANSPLANTATION OF STEM CELLS INTO SPINAL CORD
The original cell transplantation technology has been developed in the Centre for treating SCI patients. After surgically disrupting an intramedullary cyst (see Figure 1), the spinal cord defect is entirely filled up with the special gel containing foetal-derived, immature stem cells (see Figure 2). Moreover, during several months after the surgery each patient is subarachnoidally grafted with foetal-derived cells one or more times. The donor cell combination that is highly effective in generating regenerative processes in an adult nervous tissue has been previously determined by special experimental studies.
Figure 1. Dissection of the connective tissue cyst and opening access to the cord defect.
Figure 2. Infill of the spinal cord defect with the cell- containing gel implant.
FUTURE OF STEM CELLS
It has been hypothesized by scientists that stem cells may, at some point in the future, become the basis for treating diseases such as Parkinson's disease, diabetes, and heart disease.
As scientists learn more about stem cells, it may become possible to use the cells not just in cell-based therapies, but also for screening new drugs and toxins and understanding birth defects.
N.B.: This article was an e learning exercise by medical student Ms Kausalyaa Krishnabalan of Melaka Manipal Medical College , Malaysia
Rate It
Pathophysiolgy of Pathological Fracture
Posted by on Wednesday, 5th January 2011
Pathological fracture is a fracture that occurs when a bone breaks in an area that is weakened by another disease process. Causes of weakened bone varies from genetic disorders , tumours , and even chronic infection , each having its own pathogenesis which leads to pathological fracture.
Pathological fractures occur usually during normal routine activities of the patient.He may rest his hand on table when it fractured,he may be playing with grandchildren when the fracture occurs.These are only few of the examples.The reason is that the underlying disease process weakens the bone to the point where the bone is unable to perform its normal function.
Here are some of the causes of pathological fracture,whereby the pathophysiology of few of the condition will be explained briefly.
Generalized cause which include osteogenesis imperfecta , postmenopausal osteoporosis , metabolic bone disease , myelomatosis , Polyostotic fibrous dysplasia, and Paget’s disease. Secondly , local benign condition including chronic infection , solitary bone cyst , Fibrous cortical defect , chondromyxoid fibroma , aneurismal bone cyst , Chondroma , monostotic fibrous dysplasia.There are also few primary malignant tumors leading to pathological fracture which are chondrosarcoma , Osteosarcoma , Ewing’s tumor.Lastly few of the metastatic tumors , including Carcinoma breast , lung , kidney , thyroid , Colon , and prostate.
In Osteogenesis Imperfecta,the pathology lies in the disturbance in the synthesis of type I collagen, which is the predominant protein of the extracellular matrix of most tissues. In bone, this defect of extracellular matrix causes osteoporosis, which leads to an increase in the tendency to fracture. Besides bone, type I collagen is also a major constituent of dentin, sclerae, ligaments, blood vessels, and skin; therefore, individuals with osteogenesis imperfecta may also have abnormalities of these structures.
The process of collagen molecule formation starts with the synthesis of procollagen, consisting of a long triple-helix protein flanked by 2 propeptides at its 2 terminals.It is then secreted into the extracellular compartment, where the amino- and carboxy-terminal propeptides are cleaved,thus forming the functional collagen molecule. Then,fibrils are formed.Any Mutations that interfere with expression of the collagen gene, formation of the triple helix , or procollagen secretion will affect the structure and function of collagen fibrils, leading to osteogenesis imperfecta.
A number of genetic defects cause the abnormal type I collagen synthesis that leads to osteogenesis imperfecta. It generally arises from mutations in 1 of 2 genes that encode for the synthesis and structure of type I collagen: the COL1A1 gene on chromosome 17, and the COL1A2 gene on chromosome 7. Mutations in these genes leads to decrease in normal collagen. Milder forms of osteogenesis imperfecta are caused primarily by a decrease in production of normal collagen, whereas more severe forms are caused primarily by the production of abnormal collagen. These abnormalities may be dominantly inherited, or they may be the result of sporadic mutation.
Next is Postmenopausal Osteoporosis.Underlying pathology : imbalance of bone resorption and bone formation.In normal bone, there is constant matrix remodeling of bone and up to 10% of all bone mass may be undergoing remodeling at any point in time. Bone is resorbed by osteoclast cells , after which new bone is deposited by osteoblast cells.The main mechanism by which osteoporosis develops are an inadequate peak bone mass (the skeleton develops insufficient mass and strength during growth), excessive bone resorption and inadequate formation of new bone during remodeling. An interplay of these three mechanisms underlies the development of fragile bone tissue.Moreover,hormonal factors , for example the lack of estrogen( as a result of menopause) increases bone resorption,and decreases the deposition of new bone that normally takes place in weight-bearing bones. The α-form of the estrogen receptor appears to be the most important in regulating bone turnover.
In bone structure,trabecular bone is the sponge-like bone in the ends of long bones and vertebrae. Cortical bone is the hard outer shell of bones and the middle of long bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Not only is bone density decreased, but the microarchitecture of bone is disrupted. The weaker spicules of trabecular bone break ("microcracks"), and are replaced by weaker bone. Common osteoporotic fracture sites, the wrist, the hip and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on trabecular bone for strength, and therefore the intense remodeling causes these areas to degenerate most when the remodeling is imbalanced.
Next is the metabolic bone disease,in which rickets and hyperparathyroidism discussed here.As for rickets,it involves mainly dietary deficiency of Vitamin D and calcium.Vitamin D is required for proper calcium absorption from the gut. Sunlight, especially ultraviolet light, lets human skin cells convert Vitamin D from an inactive to active state. In the absence of vitamin D, dietary calcium is not properly absorbed, resulting in hypocalcemia, leading to skeletal and dental deformities and neuromuscular symptoms.(eg of food containing vitamin D are butter,egg,fish liver oil,margarine etc)
Next is Hyperparathyroidism.Osteoporosis associated with hyperparathyroidism is caused by the high parathyroid hormone secreted by overactive parathyroid gland. Excess parathyroid hormone acts indirectly on osteoclasts as they lack a PTH receptor. Instead, PTH stimulates osteoblasts, which in turn increases their expression of RANKL. RANKL is then able to bind osteoclasts which stimulates their activation which ultimately leads to the removal of calcium from the bones.
Moving on to the next cause of pathological fracture, which is Myelomatosis.Myeloma bone pain usually involves the spine and ribs, and worsens with activity. Persistent localized pain may indicate a pathological bone fracture. Myeloma bone disease is due to the release of RANKL by plasma cells and bone marrow stroma which binds to activatory RANK receptors on the osteoclast. These bone lesions are lytic in nature.(punced out lesion and pepper pot appearance on radiograph)
Next on the list is the Paget’s Disease/ Osteitis deformans.It is associated with genetic or viral etiology. Sir James Paget first suggested that the disease was due to an inflammatory process. New evidence suggests that he may have been correct and that a paramyxovirus infection is the underlying cause of Pagets Disease. No infectious virus has yet been isolated as a causative agent, however, and other evidence suggests that an intrinsic hyperresponsive reaction to Vitamin D and RANK ligand is the cause. The pathogenesis of Paget's disease involves 3 stages,which are : Osteoclastic activity , Mixed osteoclastic-osteoblastic activity and exhaustive (burnt out) stage. Initially, there is a highly increased rate of bone resorption at localized areas due to large and numerous osteoclasts (seen radiologically as an advancing lytic wedge in long bones or osteoporosis circumscripta in the skull ) .Then, the osteolysis is followed by a compensatory increase in bone formation which is induces by osteoblasts recruited to the area,leading to accelerated deposition of lamellar bone in a disorganized fashion ("mosaic" pattern), rather than the normal linear lamellar pattern. After that,the resorbed bone is replaced , marrow spaces are filled by fibrous connective tissue with a marked increase in blood vessels ( hypervascular bone ). The bone hypercellularity may then diminish leaving a dense pagetic bone ,also known as burned-out Paget disease.
As for chronic infection,osteomyelitis is one of the example.Osteomyelitis is the infection of bone or bone marrow. In general, microorganisms may infect bone through bloodstream, contiguously from local areas of infection (as in cellulitis), or penetrating trauma, including iatrogenic .Once the bone is infected, leukocytes enter the infected area, and, in their attempt to engulf the infectious organisms, release enzymes that lyse the bone. Pus spreads into the bone's blood vessels, impairing their flow, and areas of devitalized infected bone, known as sequestra form the basis of a chronic infection.Often, the body will try to create new bone around the area of necrosis. The resulting new bone is often called an involucrum.On histologic examination, these areas of necrotic bone are the basis for distinguishing between acute osteomyelitis and chronic osteomyelitis. Osteomyelitis is an infective process which encompasses all of the bone components, including the bone marrow. When it is chronic it can lead to bone sclerosis and deformity.Because of the particulars of their blood supply, the tibia, femur, humerus, vertebra, the maxilla, and the mandibular bodies are especially susceptible to osteomyelitis. Abscesses of any bone, however, may be precipitated by trauma to the affected area.
Chronic osteomyelitis can lead to pathological fracture.It is due to excessively large diapyseal separation and the formation of involucrum that is inadequate to stand the normal stress brought to bear upon the limb.Moreover,fracture is facilitated by imperfect immobilization and support of the diseased bone,and is therefore more found in single bone – humerus and femur , compared to those that have companion bone for support
The other cause of pathological fracture is Fibrous Cortical Defect ( FCD ) ,nonaggressive fibrous lesion of bone , considered to be developmental defects. It typically occurred within the metaphysis of growing long tubular bones in children, most commonly about the knee. FCDs are asymptomatic, small (<3 cm), eccentrically located, metaphyseal cortical defects; most of these spontaneously disappear. However, some evolve and enlarge into fibroxanthomas. Conversely, fibroxanthomas (>3 cm) are larger, eccentric, intramedullary lesions that abut the cortex; they have a typical, superficial, scalloping pattern in the adjacent cortex.While these lesions also can heal spontaneously (with reactive bone filling in the central lucent fibrous tissue component), they can also persist, with interval growth that continues into adulthood. Typically, fibroxanthomas are asymptomatic. However, the larger lesions may become symptomatic, with a risk of pathologic fracture. Steiner suggested that these 2 lesions are secondary to cellular proliferation due to aberrations in local development.
Next is the Solitary bone cyst ,a benign, fluid-filled, radiolucent lesion that may appear in virtually any bone, but typically, it is found in either the proximal humerus or proximal femur. This lesion is found almost exclusively in children.It often leads to thinning of adjacent areas of bone, such that fracture or pain from microfracture may occur. When such cysts are immediately adjacent to a growth plate, they are referred to as active cysts, and when they have achieved some distance from the growth plate, they are considered to be latent cysts. It usually presents as a unifocal (one bone) problem, affecting patients who are skeletally immature.
Then comes the aneurysmal bone cyst (ABC) , an expansile cystic lesion that most often affects individuals during their second decade of life and may occur in any bone in the body. Although benign, it may become locally aggressive causing extensive weakening of the bony structure and impinge on the surrounding tissues. The true etiology and pathophysiology remain a mystery. However,different theories about several vascular malformations were suggested, these include arteriovenous fistulas and venous blockage. The vascular lesions then cause increased pressure, expansion, erosion, and resorption of the surrounding bone. The malformation is also believed to cause local hemorrhage that initiates the formation of reactive osteolytic tissue , further leading to the pathological fracture.
Moving on with chondromyxoid fibroma (CMF) , a rare benign tumor of bone. The etiology is unknown however, one report has pointed to an error in chromosome 6.The tumor arises from the cartilage-forming connective tissue of the marrow space. Histologically, as its name implies, this benign cartilaginous neoplasm consists of chondroid, myxoid, and fibrous tissue in variable amounts.Osteoclast-like giant cells may also be present, as may small cysts and hemorrhagic zones. Focal calcification is found microscopically in approximately one fourth of patients, although any gross evidence of calcification is rare.
Next is the fibous dysplasia , which is the skeletal developmental anomaly of the bone-forming mesenchyme that manifests as a defect in osteoblastic differentiation and maturation. It can affect any bone in the body. It is a nonhereditary disorder of unknown cause.However , there are suggestion that it may be due to abnormal growth process is related to a mutation in the gene that encodes the subunit of a stimulatory G protein (Gsα) located on chromosome 20.As a consequence of this mutation, there is a substitution of the cysteine or the histidine—amino acids of the genomic DNA in the osteoblastic cells—by another amino acid, arginine. The osteoblastic cells will elaborate a fibrous tissue in the bone marrow instead of normal bone. In fibrous dysplasia, lesions are characterized by woven ossified tissue and extensive marrow fibrosis. Mechanical quality of bones is decreased. As a consequence of this bone fragility, patients have an increased risk of fracture. Incidence of fractures is around 50% of cases.The risk of fractures or bone deformity is higher in the long bones, such as the femur, tibia, and humerus, but all the bones can be affected. There are 4 disease patterns recognized which are monostotic,polyostotic,cherubism, and craniofacial form.The monostotic type most frequently occurs in the rib (28%), femur (23%), tibia or craniofacial bones (10-25%), humerus, and vertebrae, in decreasing order of frequency.This form may present with pain or a pathologic fracture in patients aged 10-70 years, but this form most frequently occurs in those aged 10-30 years.
Next is Chondrosarcoma , a malignant tumor of cartilaginous origin in which tumor matrix formation is entirely chondroid in nature. Chondrosarcomas are classified as central (originating within the intramedullary canal) or peripheral. Rarely, they arise as juxtacortical lesionsTumors are predominantly axial most commonly involving the pelvic bones, femur, humerus, ribs, scapula, sternum, or spine. In tubular bones, the metaphysis is the most common site of origin. The proximal metaphysis is more frequently involved than the distal end of the bone. Involvement of the distal humerus is most unusual. Chondrosarcoma rarely occurs in the hands and feet; such occurrences usually arise as a complication of a multiple enchondromatosis syndrome. Chondrosarcoma arising de novo in the hands and feet is extremely unusual.The tumor may occasionally occur as a pathologic fracture.
Then,there is also osteosarcoma, the most common primary malignancy of bone. It is a malignant connective tissue tumor whose neoplastic cells present osteoblastic differentiation.The tumour may be localised at the end of the long bone. Most often it affects the upper end of tibia or humerus, or lower end of femur. The tumor is solid, hard, irregular ("fir-tree," "moth-eaten" or "sun-burst" appearance on X-ray examination) due to the tumor spicules of calcified bone radiating in right angles (Codman’s triangle). Surrounding tissues are infiltrated.The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumour. Tumor cells are very pleomorphic. These cells produce osteoid describing irregular trabeculae (amorphous, eosinophilic/pink) with or without central calcification (hematoxylinophilic/blue, granular) - tumor bone. Tumor cells are included in the osteoid matrix. Depending on the features of the tumour cells present (whether they resemble bone cells, cartilage cells or fibroblast cells), the tumour can be subclassified. The affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture)
Next,the Ewing sarcoma , a malignant round-cell tumor. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, and the ribs.Genetic exchange between chromosomes can cause cells to become cancerous, like these cells from metastasized Ewing sarcoma. Ewing sarcoma is the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11.EWS/FLI functions as the master regulator.Other translocations are at t(21;2) and t(7;22)The radiographic appearance of Ewing sarcoma may vary highly from a lytic one to a dominantly sclerotic one,and patient may present with pathological fracture.
Lastly is the bone metastases.The behavior of bone metastases can be characterized as osteoblastic, osteolytic or mixed, based on the effect on surrounding bone. All are due to dysregulation of the normal bone remodeling mechanisms, caused by tumor-host cell interactions. Osteoblastic tumors cause an abnormal formation of bone by direct secretion of bone extracellular matrix (ECM) proteins and by indirect stimulation of osteoblasts.Osteolytic tumors cause abnormal resorption of bone by proteolytic enzymes and through actions on osteoclasts. Osteolysis can release sequestered growth factors from the ECM, resulting in a cyclical feedback loop that leads to further stimulation of osteoclasts and continued bone resorption. As bone mass is lost, tumors can then continue to proliferate in their place,grow in size,causing further weakening of bone and thus leading to pathological fracture.
It is important to look into the underlying causes of pathological fracture in order for the treatment to be effective and safe.Some pathologic fracture require the same treatment as the other fractures,while others may require a highly specialized care.In a nutshell,pathological fracture involves a spectrum of causes wherein lies the modality of the treatment and care we will be giving to our patients.
Reference:
Apley’s System of Orthopaedics and Fractures 8th Edition – Louis Solomon ,
David J. Warwick , Selvadurai Nayagam
http://orthopedics.about.com/cs/brokenbones/g/pathologic.htm
http://www.wheelessonline.com/ortho/pathologic_fracture
http://emedicine.medscape.com/article/411919-overview
http://en.wikipedia.org/wiki/Osteoporosis
http://en.wikipedia.org/wiki/Hyperparathyroidism
http://en.wikipedia.org/wiki/Myelomatosis
http://en.wikipedia.org/wiki/Paget%27s_disease_of_bone
http://emedicine.medscape.com/article/1254784-overview
http://emedicine.medscape.com/article/388738-overview
http://emedicine.medscape.com/article/389714-overview
http://emedicine.medscape.com/article/1255262-overview
http://emedicine.medscape.com/article/388869-overview
http://en.wikipedia.org/wiki/Osteosarcoma
http://emedicine.medscape.com/article/389464-overview
http://emedicine.medscape.com/article/1257331-overview
http://emedicine.medscape.com/article/389590-overview
NB: This article was an e-learning excercise by Siti Raidah bt Mohd Yassin a student of Melaka Manipal Medical College Malaysia
Rate It
Why we are No. 1 › 
