Cancer Biopsy and Risk of Metastases

Last year someone asked if biopsy of a tumor could result in the spread of the cancer. There are a few unathorative websites that claim this is the case. Those sites also happen to be touting "alternative" treatments for cancer.

A recent publication The impact of preoperative breast biopsy on the risk of sentinel lymph node metastases: analysis of 2502 cases from the Austrian sentinel node biopsy study group by Peters-Engl et al (full free text here) concluded that:

based on the present data, is that preoperative breast biopsy does not cause artificial tumour cell spread to the SLN, with possible negative impact on the prognosis of breast cancer.

These results disagreed with those of Hansen et al in a paper titled Manipulation of the Primary Breast Tumor and the Incidence of Sentinel Node Metastases From Invasive Breast Cancer (summary here).

But go here and read what Dr. Hansen has to say about her study before you make a decision about the safety of cancer biopsy.

"This study does not link biopsy with spread [of breast cancer]," Hansen tells WebMD via email. "We have not changed our practice and do not plan to. We still prefer to perform a needle biopsy to confirm the diagnosis of cancer and then will proceed at another time to definitive surgical management."

Neoplasms

For an excellent easily understood review about cancer proceed to this National Cancer Institute website and click through all 61 slides.




TERMS

Neoplasm: (neo= new; plasm= form) an uncontrolled growth of new cells, may be benign or malignant

Tumor: a mass; a neoplasm

Cancer: any kind of malignant neoplasm

Malignant: capable of spreading throughout the body and causing death

Carcinoma: a malignant neoplasm of epithelial cells

Sarcoma: a malignant neoplasm of mesenchymal (tissue derived from mesoderm) tissue

Our bodies are constantly shedding dead cells and growing new cells. Remember that a neoplasm is and uncontrolled growth of new cells. It is not normal growth.



Normal cell growth is controlled by proto-oncogenes. These genes generally encode proteins which control normal cell growth. But when proto-oncogenes undergo mutation, they may become oncogenes. You can learn much more about oncogenes here.



The body has evolved mechanisms to repair damaged DNA.

Cancer is caused by mutation of somatic cells. Some individuals have inherited genetic mutations that predispose them to develop certain types of cancer. It may take as few as 3 and as many as 20 mutations for a proto-oncogene to become an oncogene. Thus, cancers are frequently found in aged individuals.

How does DNA become damaged? Chemical carcinogens, ionizing radiation and viral infection have all been linked to DNA injury. Many, many more causes and risk factors for cancer can be found at this NIH website.

Does fluoridated water cause cancer? Experts at NIH say there is no evidence that it does.

In 1993, the Subcommittee on Health Effects of Ingested Fluoride of the National Research Council, part of the National Academy of Sciences, conducted an extensive literature review concerning the association between fluoridated drinking water and increased cancer risk. The review included data from more than 50 human epidemiological studies and six animal studies. The Subcommittee concluded that none of the data demonstrated an association between fluoridated drinking water and cancer (5). A 1999 report by the CDC supported these findings. The report concluded that studies to date have produced “no credible evidence” of an association between fluoridated drinking water and an increased risk for cancer (2).

However, if you do a google search you will find over 2.5 million links claiming differently. Could there really be a conspiracy to cover up the effects of fluoride treatment on cancer? I doubt it.

Tumor suppression genes can be thought of as genes that provide a "stop" signal. If these genes are mutated normal cell growth can become uninhibited. Much more about tumor suppressor genes here.

An important consideration in cancer biology is the speed of tumor growth. Go to this website to learn about cell growth and doubling time.



Angiogenesis is the process of growing a new blood supply. It's very important in tumor biology. There is a slide presentation on understanding the role of angiogenesis in cancer at this NCI website.

Grading and staging of neoplasms are done to aid in treatment decisions. Cancer grading is a pathologic exercise that determines the degree of differentiation of a tumor. Cancer staging is a clinical exercise that evaluates the behavior of a neoplasm. Learn more about grading and staging at this website.

Early detection of cancer is important for the most effective treatment. Learn about early detection of some cancers here, here and here.

Want further training in understanding cancer in general and specific tumors? Go to this government training website to continue your training.

Vaccination Via Tattoo

German scientists have reported that vaccines delivered using a tattoo needle produce antibody responses 16 times greater than those delivered by intramuscular injection.

Hemodynamics - Thrombosis, Embolism, Shock

A thrombus is a stationary mass of blood elements that remains attached to its place of origin along the wall of a blood vessel.

Thrombi are not clots although they are partially made up of clotted blood. Unlike most clots, a thrombus is always the result of a pathologic event. Clots are normal (usually) and occur outside a blood vessel.

The formation of a thrombus is not initially dependent on the clotting process. Thombi begin endothelial injury and an initial platelet clump. Layers of platelets are added followed by the adherence of white blood cells. A clot then adds volume as the thrombus grows.

You can find a full text article concerning deep vein thrombosis here and another full text article here.



An embolus is an intravascular object (air, tumor fragment, broken off thrombus, calcium fragments) that circulates in the bloodstream until it becomes lodged in a vessel obstructing the blood flow.

Ischemia is a lack of oxygen supply to a tissue usually due to obstruction of blood flow.



Lack of oxygen supply to a tissue can result in a tissue death called an infarct

See photos of an infarct of the heart here.

Shock is a state of systemic low blood flow. It can occur due to a loss of blood or because cardiac output is reduced.

Cardiogenic shock occurs when the heart is incapable of maintaining blood pressure. You can read much more about cardiogenic shock here.

Hypovolemic shock is a result of an underfilled vascular space, usually the result of hemorrhage. It can also be caused by fluid loss in cases of severe burns or diarrhea. Read more about hypovolemic shock here.

Septic shock is associated with systemic bacterial infections (sepsis) usually gram-negative bacterial infections. It is due to a massive inflammatory response to the infection. Read more about septic shock here.

Hemodynamics - Edema

Above figure from Heartzine.Go there to learn about circulatory system.

To review your anatomy of the circulatory system go to this great website at the Texas Heart Institute.

60% of the human body is water. So an average person of 155 lbs is made up of 93 lbs of water and 62 lbs of solids. The 42 liters of water can be broken down this way:

Extracellular
Interstitial (space outside the blood vessels and in between cells) 8 liters
Plasma 3 liters
Cerebrospinal fluid and other 6 liters
For a total of 17 liters

Intracellular
A total of 25 liters (including Red Blood Cells)

Blood pressure is the force of blood pushing against the walls of arteries. It's expressed as the number of millimeters it can force a column of mercury upwards.

Normal blood pressure is a reading of 120/80 or lower. High blood pressure is a reading of 140/90 or greater.

Another type of pressure is osmotic pressure. Osmotic pressure is the amount of hemodynamic pressure that must be applied on the side with low water concentration to prevent water from passing into the saltier side.

Go to this Colorado State osmotic pressure simulator site and you can see the effects of increasing or decreasing solute on either side of a permeable membrane.

You can learn about osmotic pressure here (interactive) and here (physics).

Edema is a shift of water from the vascular space into another compartment, usually the interstitial compartment. Here is one website that discusses edema in general.

Low protein edema also called a transudate, occurs when there is excess venous pressure (hydrostatic edema) or low plasma osmotic pressure. Each of these conditions allows water to leave the vascular spaces and enter the tissue spaces.

One example of low protein edema is varicose veins due to excess venous pressure. Read more about varicose veins here.

Osmotic edema is another type of low protein edema. It occurs when plasma albumin levels are abnormally low allowing water to escape from the vascular space to the interstitial space. Osmotic edema is often associated with liver disease because the liver is the primary producer of albumin.

Generalized edema (anasarca) is another example of low protein edema.

High Protein Edema is the fluid accumulation seen in inflammation. Inflammatory edema would be seen in a sprained joint.

Lymphedema is due to obstucted lymphatics. See more here.



Cerebral and pulmonary edema can be fatal. Swelling of the brain results in increased pressure on the brain. Pulmonary edema can impair gas transport and exchange or encourage bacterial growth.

William Harvey and Blood Circulation

William Harvey is the 17th century physician who hypothesized that blood moved in a circle. This was quite different from the accepted view of the time. Galen had postulated 1700 years previously that there were two kinds of blood, arterial and veinous, each with their own pathway to the tissues where it was consumed.

Harvey wrote: Since all things, both argument and ocular demonstration, show that the blood passes through the lungs and heart by the force of the ventricles, and is sent for distribution to all parts of the body, where it makes its way into the veins and porosites of the flesh, and then flows by the veins from the circumference on every side to the centre, from the lesser to the greater veins, and is by them finally discharged into the vena cava and right auricle of the heart, and this in such a quantity or in such a flux and reflux thither by the arteries, hither by the veins, as cannot possibly be supplied by the ingesta, and is much greater than can be required for mere purposes of nutrition; it is absolutely necessary to conclude that the blood in the animal body is impelled in a circle, and is in a state of ceaseless motion.
That is one hell of a sentence!

Harvey knew blood moved in a circle but he was unable to determine exactly how. He did not have the technology to observe the small capillaries that connected the arterial and veinous vessels.

Harvey was one of the first to use the scientific method in his work. He said:

I profess to learn and teach anatomy not from books but from dissections,not from the tenets for Philosophers but from the fabric of Nature.

You can learn more about William Harvey here.

Repair: Recovery from injury

After injury and inflammation comes repair. Repair is the restoration of normal structure and function to injured tissue.

Read about it here.

Tissue regeneration requires an intact supporting stromal framework.

One element of this framework is the extracellular matrix. Read about extracellular matrix here.

The other stromal framework element is the basement membrane.


Photomicrograph from here.

Without the support of the extracellular matrix and basement membrane, tissues cannot return to normal and scarring occurs.

Angiogenesis is the growth of new blood vessels into the wound. View this NIH tutorial on angiogenesis in relation to tumor metastasis. It's a slide show, so just keep clicking on the arrow in the upper right corner.

There is also an entire issue of Nature devoted to angiogenesis with free text available here. This article is especially good.

Scar development follows angiogenesis. Read about scar development here.

What about tissue repair of the perineal region that is torn during childbirth?
You can read about this at these links here, here and here. Or you can listen to an NPR report on the topic here.

Stem Cells

Above image from here.

Stem cells are primative, undifferentiated cells that have the capacity to proliferate and differentiate into more mature types of cells.

Some forms of tissue regeneration require stem cells.

You can go here to see animations about stem cells (you need Flash Player installed).

There is also stem cell information in lay terms at the NIH Stem Cell Information website.

Embryonic stem cells are obtained from human fertilized eggs called blastocysts. These stem cells are often refered to as "totipotent stem cells".

You can view an animated tutorial on human embryonic stem cells at this website and also at this website.

Adult stem cells are multipotent and are normally obtained from the bone marrow. A bone marrow transplant can be considered a stem cell transplant.

More recently, stem cells have been obtained from umbilical cords of recently born babies.

Stem cells were first cultured at my Alma Mater, The University of Wisconsin by James Thomson (paper cited above). Lots of stem cell info at this UW website.

Temperature Regulation

The human body can regulate its core temperature to between 98 and 100 degrees F. If skin temperature drops below 37 degrees C. the body attempts to conserve heat by constricting the blood supply to the body surface. Shivering is the bodys attempt to produce more heat through muscle activity. Because no external work is performed during shivering, all the energy released is in the form of heat. Here is a short review on body temperature regulation. Also here.

Hypothermia (stage 1) occurs when the body temperature reaches 95 degrees or lower. Read about hypothermia at this Coast Guard website.

Hyperthermia occurs when the body produces more heat than it can dissipate. Body temperatures above 104 degrees F are life threatening. You can listen to scientist talk about how the human body copes with heat at this NPR website.

Fever (pyrexia)is an increase in body temperature as a response to bacterial or viral infection or to tissue injury. It's a temporary elevation in the bodies thermoregulatory setpoint. Generally, fever is not an illness because it's a defense response against infections. Body temperature can also increase due to hard exercise; ovulation; excess thyroid secretions and central nervous system damage. Cancer can also induce fever. More about fevers here.

Inflammation

All disease is due to cell injury. Cell injury results in inflammation. The cardinal signs of inflammation were first described by Cornelius Celsus. You can actually read a translation of Celsus' De Medicina here.



You can learn a lot about Acute Inflammation at this website; chronic inflammation and healing and repair.

The pathogenesis of inflammation involves the leukocyte adhesion cascade. You can learn more about this process here.

This process is very important. Leukocyte Adhesion Deficiency Syndrome is a very rare genetic disorder caused by lack of, or deficiency in production of the cell surface molecule CD18.



Persistent injury can result in chronic inflammation. The above is one example. A Nobel Prize was awarded for this disovery.



The process of inflammation is very complex. There are many molecules involved and a few of them can be seen in the above figure showing airway smooth muscle mediators of inflammation.

More on molecular mediators of inflammation can be found HERE.

Plasma-derived mediators of inflammation:

Clotting system - read this.

Complement system - read this. We will discuss the complement system further under immunity. But the complement system generally has an under appreciated role in inflammation.

Kinin system - read this. [pdf available]

Cell-derived mediators of inflammation:

Vasoactive amines - read this and this.

Cell membrane factors - read this and this.

Cytokines (here and here)and Chemokines (here and here).

Reactive oxygen compounds - read this and this.

Chronic inflammation differs from acute inflammation. Read about it here.

Mitochondrial Diseases

Yes there are diseases due to malfunctioning mitochondria. You can find an introduction here at the United Mitochondrial Disease Foundation. Many of these diseases are due to mutations in the mitochondrial DNA.

If you are really interested I found a free full text article about mitochondria and mitochondrial diseases here (but you have to register).

Healing Powers of Hyperbaric Oxygen

Several diseases can be treated with hyperbaric oxygen. Read about some of them here at the Medical College of Wisconsin.

As for the use of hyperbaric oxygen therapy in cancer, there doesn't seem to be any firm evidence that it is useful. There is a fair bit of literature on the subject but I couldn't find any clinical trials that show the effectiveness of HBO treatment on cancer.

Necrosis

Go here to see examples of coagulative necrosis and resulting infarcts both at the gross level and histological level. Keep clicking the 'right' arrow to see more examples. What is the most common cause of coagulative necrosis?

Examples of liquefactive necrosis can be seen starting here. Notice the photo of the macrophages cleaning up debris from an area of liquefactive necrosis in the brain.



Examples of fat necrosis start here.





Next is, you got it, the cheesy caseous necrosis seen in TB infected lung.



The Mycobacteria need to create these extensive areas of necrosis so they can be coughed out of the lungs and passed on to another individual.

Gangrene is next. Don't click on the link if you are feeling ill. The photo is of disembodied toes. We all know what can happen if you get frostbite.



Fibrinoid necrosis in hypertension.



Remember we talked about accumulation of abnormally folded proteins. Check out this photo of amyloid accumulation.

Then there is aging. Wear and tear (growing old) results in the accumulation of lipochrome in the liver. This is cellular debris that is sequestered within the cytoplasm.

Cell Adaptation

Here are some examples of alterations in cell growth.



You can read more detail about muscle atrophy here.



Have you got that going problem? Maybe it's a growing problem. Benign prostate hyperplasia cartoon. Read more about BPH here.

Learn more about metaplasia here.

An example of cervical dysplasia. Keep clicking for more examples of dysplasia.

Here the entire epithelium is dysplastic so you have a full blown neoplasm. The basement membrane is intact however, so the cancer is not yet malignant.

APOPTOSIS

More than you will ever want or need to know about apoptosis at this good website.



I borrowed this picture from the above website. It compares the process of apoptosis and necrosis.

You can read about the p53 tumor suppressor gene, apoptosis and prostate cancer here. We will cover this in more detail when we discuss neoplasms.

Guinea Worm and the Medical Practice Symbol

I have mentioned that I am reading "Parasite Rex" by Carl Zimmer. The book is just as I expected. Wonderfully written, scary stories and anecdotes about parasites. I especially like his discussion of how the term "parasite" arose.

The word literally means "beside food," and the Greeks originally had something different in mind when they used it, referring to officials who served at temple feasts. At some point the word slipped its etymological harness and came to mean a hanger-on, someone who could get the occasional meal from a nobelman by pleasing him with good conversation....

But that is neither here nor there. Let's discuss guinea worm infection and its possible association with the symbol of medical practice....the Caduceus. The study of parasitology is filled with stories concerning history and especially biblical references.


Guinea worm, or Dracunculus medinensis, is a roundworm found in India, West and Central Africa and parts of the Middle East. The worms are found in the subcutaneous tissues of humans and the female worm can be over 30 inches in length. You become infected with guinea worm by drinking water that is contaminated with small, freshwater crustaceans that are themselves infected with guinea worm larvae. (Cyclops).

When the crustacean is consumed in contaminated drinking water, the guinea worm larvae in the Cyclops is released and makes its way through the intestinal wall, crosses the abdominal mesentaries, penetrates the abdominal muscles and make their way to the subcutaneous tissues. Fertilized females release their live larvae by penetrating the skin about a year after infection. Infected individuals often wind the body of the emerging female around a small stick so as to collect the entire adult worm rather than breaking it off in the body.

Obviously, the way to prevent this infection is to provide a clean, uncontaminated, source of drinking water. Also, the live larvae of the adult female need to be released into fresh water in order to find a Cyclops to infect as an intermediate host. So please do not go swimming or wading in fresh water if you find yourself with a female guinea worm emerging from your body.

Now, what you ask does this have to do with the symbol of medical practice? Well, you need to open your bible to Numbers 21:6-9:

And the Lord sent fiery serpents among the people, and they bit the people; and much people of Israel died.

Therefore the people came to Moses and said, We have sinned, for we have spoken against the Lord, and against thee; pray unto the Lord, that he take away the serpents from us. And Moses prayed for the people.

And the Lord said unto Moses, Make thee a fiery serpent, and set it upon a pole; and it shall come to pass, that every one that is bitten, when he looketh upon it, shall live.

And Moses made a serpent of brass, and put it upon a pole; and it came to pass, that if a serpent had bitten any man, when he beheld the serpent of brass, he lived.

Here we have talk of a serpent on a pole. Guinea worm, by the way, causes intense pain (like fire) when it emerges from a blister on an arm or leg.


Where Zimmer gets it wrong is stating that "But it may be that that person's invention was remembered in the symbol of medicine, known as the caduceus: two serpents wound around a staff." [Chapt. 1, pg. 2]

Actually, the symbol of medicine is not the winged staff with two serpents. That would be the "Caduceus of Mercury" or the "Karykeion of Hermes". This is actually a symbol of commerce.


The actual symbol of medicine is the Staff of Asclepius. A staff, or stick, with a single snake wrapped around it. You can find all you want to know about the difference between a caduceus and the staff of Asclepius here at the website of New Zealand physician Dr. Blayney.

Why is the caduceus a symbol of medicine in the USA? Blame it on the US Army Medical Corps.

Prefixes and Suffixes

PREFIXES

a - without or not

an - without

angio - vessel

arthro - joint

brady - slow

dys - difficult or bad

homeo - similar

hyper - above or excessive

hypo - deficiency or beneath

inter - between

intra - within

mal - bad

micro - small

mega - large

necro - death

neo - new

para - beside

peri - around

osteo - bone

para - beside

peri - around

phleb - vein

poly - many

pro - before

pseudo - false

pyo - pus

steno - narrow, compressed

syn - together with

tachy - rapid

SUFFIXES


algia - pain

emia - blood

genesis - generation of

iasis - a process, especially a morbid one

ism - condition

itis - inflammation of the part named

lysis - to dissolve

megaly - large

oma - tumor

osis - full of

pathy - disease

penia - poverty, a deficiency

plasia - to form

plegia - a paralyzed state

ptosis - downward displacement

sclerosis - hardening

stasis - standing still

trophy - nourish

Some Terms

Etiology. The cause of disease. Disease is either caused by genetic or acquired factors. Disease results from cell injury.

Pathogenesis. How the disease develops. The sequence of events or physiologic processes that result in disease.

What is disease? One definition is: An interruption, cessation, or disorder of body functions, systems, or organs. Another is the pattern of response of a living organism to some form of injury with a resultant alteration in normal function.

For a long list of diseases and information about them go to the disease list at CDC.

Injury. Damage or harm caused to the structure or function of the body.

Infection. A detrimental colonization of a host organism by a foreign species.

Angiogenesis. The process of blood vessel formation.

Apoptosis. Programmed cell death. Usually a normal biological function.

Atherosclerosis. A disease of arteries characterized by chronic inflammation, scarring and cholesterol deposits in large and medium-sized arteries.

Atrophy. A shrinkage in the size of cells, organs and tissues.

Dysplasia. An abnormal development of a body tissue.

Embolism. Obstruction of a blood vessel by an abnormal mass formed elsewhere in the circulation and transported to its point of impaction.

Fibrosis. The formation of fibrous tissuek, usually as a reaction to chronic inflammation.

Gangrene. Combination of tissue necrosis with infection.

Homeostasis. The maintenance of a steady state in respect of physiologic function in the face of environmental variation.

Hyperplasia. An increase in the number of cells in a given population.

Hypertrophy. An increase in the size of individual cells usually due to increase workload.

Hypoxia. A reduction in the supply of oxygen.

Impaction. The lodgement of some abnormal mass in a hollow muscular tube causing blockage of the lumen.

Infarct. An area of tissue necrosis caused by a lack of blood supply to the affected region.

Ischemia. The pathophysiologic state in which the blood supply of an organ or tissue is reduced below its metabolic needs.

Metaplasia. A change in a cell population from one fully differentiated form to another fully differentiated form.

Necrosis. The death of a tissue within a circumscribed area.

Thrombosis. The formation of an abnormal intravascular mass from the constituents of flowing blood.

Thrombus. An abnomal intravascular mass formed from the constituents of flowing blood.

A Short History of Pathology

Cornelius Celsus (30 BC - 38 AD) describes clinical features of inflammation. Calor, rubor, dolor, tumor.

Galen (131 - 201 AD) a physician to the Roman gladiators. He didn't dissect human cadavors but Galen's great powers of observation allowed him to study, classify, and record anatomic and pathologic observations. Some of his observations, like the crab-like growth of cancers, were correct.

Leonardo da Vinci (1452 -1519) was one of the first to dissect humans in the quest for answers about the human form.

Andreas Vesalius (1514 - 1564) dissected humans and published a book De Humani Corporis Fabrica, 1543. His drawings of the human skeleton are especially noted for their detail and artestry.



More images and pages of his book can be seen here.

Antonio Benivieni (1443 - 1502) is credited for performing the first autopsies on humans to determine the cause of death. Not much is known about Benivieni's life.

Anatomy as a subject of study became acceptible in the 17th century.

Marie-Francois-Xavier Bichat (1771 - 1802), a French physcian was one of the first 'modern' pathologists and is considered by many to be the father of histology and pathology.

John Hunter (1728 - 1793), an Englishman who devised a method for preserving diseased tissues so they could be studied in the future.

Carl Rokitansky (1804 – 1878) is said to have performed over 20,000 autopsies and oversaw the performance of 60,000 more. He made important observations concerning multiple sclerosis.

Rudolf Virchow (1821 - 1905), used the microscope to learn that diseases arise from alterations within tissues and cells.

Julius Cohnheim (1839–1884), Virchow's student, devised experiments to study inflammation as it happened rather than after the tissue was dead. The Father of Experimental Pathology.

Some information about these pathologists was obtained here.

How to Use PubMed

First go HERE to the PubMed website.

In the empty "search box" at the top, middle of the page, type your search term.

For example, type cellular injury. Then hit enter or click on "go".

You will see that there are 105635 articles that refer to cellular injury. Of these 105635 articles, 15099 are review articles (these numbers change as new articles are added to the database).

Clicking on article #2 will bring up the title, authors, abstract and tell you which journal published the article. To the left of the abstract, you will see links to a series of related journal articles.

Go to the top of the page and click on the History tab. On this page you will see #1 Search cellular injury. To the far left you will see the number of journal articles.

Now type ischemic in the empty search box at the top of the page and click on "go".

You see that there are 114951 articles referring to the term "ischemic". [Note: this number can change daily with the addition of new journal articles into the library.]

Click on the History tab again.

Now you see a list of both your search terms - cellular injury and ischemic.

Type this exactly in the empty search box: #1 AND #3 ("AND must be captalized), then click on "go".

Now you see that there are 8856 journal articles that contain both terms. If you had typed #1 OR #3 you would have obtained 211730 articles that contain one term or the other. If you had typed #1 NOT #3, you would have obtained 96779 articles containing the term "cellular injury" but not containing the term ischemic

Go to the upper left hand part of the page where the 'tabs' are located and click on "Limits".

This page allows you to greatly refine your search of cellular injury AND/OR/NOT ischemic. Let's say you only want to see articles printed in english. Under "Language" click the box marked english.

Let's say you only want to see articles referencing female humans. Just click on the "Human" and "Female" boxes. Click the box that says "links to free full text" to find the entire article for free.

Go to the bottom of the page and click on "Go". Up pops the 1216 articles in english about "cellular injury" but without the word "ischemia" specifically concerning "human" "females".

Click on article #1 and the abstract pops up. Notice that on the right hand side of the page containing the abstract, there is a box that says Journal of Invasive Cardiology. If you click on that box the entire article will pop up. More often there will be a free text box in that location and you can download a pdf file of the article.

If you start a search with new terms, remember to unclick the 'Limits' box or you will only get articles in english that reference humans and females.

There are many, many other databases (accessible on the library computers) and search engines (Google) that can be used to find information. But how do you know which information or articles to trust?

Here are a few general rules:

Expertise: Most of the papers you find in PubMed have been written by experts and then peer reviewed by experts. Websites that end in .gov, .org, .edu are surely more likely to provide valid information than what you find in many .com websites. Resources like Quackwatch are useful in determining the value of many medical information websites.

Experience: People tend to trust the advice of "experienced" individuals. This is because they are expected to have accumulated knowledge over time. One has to be careful here because in rapidly changing situations (like science), you need to be sure the "experienced" person has kept up with the changes and new discoveries.

Verifiability: Claims of medicine and science need to be verified or scientifically repeatible. That is why we can typically be assured that FDA approved drugs will do what the drug company claims they will do. Remember Ronald Reagans advice to trust, but verify.

Disinterest: A car salesman tells you that the car that he is about to sell you is the best in the world and will be trouble free for 15 yrs. Maybe it will, but do you believe the car salesman? No, because he is about to make money upon selling you the car. That is why most journals require full disclosure of whether scientists are funded by companies that have an interest in the publication.

A simple Google search is also well worth doing. A Google search will bring up the names of many government and non-government websites that contain a lot of useful information. The advantage of these sites are that they present information in layman terms.