Pharmacy

Erectile dysfunction

2009-03-06T00:57:00.000-08:00

From Wikipedia, the free encyclopedia
(Redirected from Sexual impotence)

Erectile dysfunction (ED or (male) impotence) is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis sufficient for satisfactory sexual performance.

An erection occurs due to hydraulic effects due to blood entering and being retained in sponge-like bodies inside the penis. During intercourse, the process is initiated when sexual arousal is transmitted from the brain to nerves in the pelvis. There are various and often multiple underlying causes, some of which are treatable medical conditions. The most important organic causes are cardiovascular disease and diabetes, neurological problems (for example, trauma from prostatectomy surgery), hormonal insufficiencies (hypogonadism) and drug side effects. It is important to realise that erectile dysfunction can signal underlying risk for cardiovascular disease.

There is often a contributing and complicating and sometimes a primary psychological or relational problem. Psychological impotence is where erection or penetration fails due to thoughts or feelings (psychological reasons) rather than physical impossibility; this can often be helped. Notably in psychological impotence, there is a strong response to placebo treatment. Erectile dysfunction, tied closely as it is to cultural notions of potency, success and masculinity, can have severe psychological consequences. There is a strong culture of silence and inability to discuss the matter. In reality, it has been estimated that around 1 in 10 men will experience recurring impotence problems at some point in their lives.

Besides treating the underlying causes and psychological consequences, the first line treatment of erectile dysfunction consists of a trial of PDE5 inhibitor drugs (the first of which was sildenafil or Viagra). In some cases, treatment can involve prostaglandin tablets in the urethra, intracavernous injections with a fine needle into the penis that cause swelling, a penile prosthesis, a penis pump or vascular reconstructive surgery.

The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina. It is now mostly replaced by more precise terms. The study of erectile dysfunction within medicine is covered by andrology, a sub-field within urology.

Blood Pressure (last part) : Pathophysiology

2009-01-24T06:22:00.000-08:00

from Wikipedia.org

High arterial pressure

Arterial hypertension in itself it is not generally an acute problem; see hypertensive emergency. But because of its long-term indirect effects (and also as an indicator of other problems) it is a serious worry to physicians diagnosing it.
Main complications of persistent high blood pressure.

All levels of arterial pressure put mechanical stress on the arterial walls. Higher pressures increase heart workload and progression of unhealthy tissue growth (atheroma) that develops within the walls of arteries. The higher the pressure, the more stress that is present and the more atheroma tend to progress and the heart muscle tends to thicken, enlarge and become weaker over time.

Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysms, and is the leading cause of chronic renal failure. Even moderate elevation of arterial pressure leads to shortened life expectancy. At severely high pressures, mean arterial pressures 50% or more above average, a person can expect to live no more than a few years unless appropriately treated.

In the past, most attention was paid to diastolic pressure; but nowadays it is recognised that both high systolic pressure and high pulse pressure (the numerical difference between systolic and diastolic pressures) are also risk factors. In some cases, it appears that a decrease in excessive diastolic pressure can actually increase risk, due probably to the increased difference between systolic and diastolic pressures (see the article on pulse pressure).

Low arterial pressure

Blood pressure that is too low is known as hypotension. The similarity in pronunciation with hypertension can cause confusion. Hypotension is a medical concern only if it causes signs or symptoms, such as dizziness, fainting, or in extreme cases, shock.

When arterial pressure and blood flow decrease beyond a certain point, the perfusion of the brain becomes critically decreased (i.e., the blood supply is not sufficient), causing lightheadedness, dizziness, weakness or fainting.

However, people who function well, while maintaining low arterial pressures have lower rates of cardiovascular disease events than people with normal arterial pressures.

Sometimes the arterial pressure drops significantly when a patient stands up from sitting. This is known as orthostatic hypotension (postural hypotension); gravity reduces the rate of blood return from the body veins below the heart back to the heart, thus reducing stroke volume and cardiac output.

When people are healthy, the veins below their heart quickly constrict and the heart rate increases to minimize and compensate for the gravity effect. This is carried out involuntarily by the autonomic nervous system. The system usually requires a few seconds to fully adjust and if the compensations are too slow or inadequate, the individual will suffer reduced blood flow to the brain, dizziness and potential blackout. Increases in G-loading, such as routinely experienced by acrobatic jet pilots 'pulling Gs', greatly increases this effect. Repositioning the body perpendicular to gravity largely eliminates the problem.

Other causes of low arterial pressure include:

* Sepsis
* Hemorrhage - blood loss
* Toxins including toxic doses of blood pressure medicine
* Hormonal abnormalities, such as Addison's disease

Shock is a complex condition which leads to critically decreased perfusion. The usual mechanisms are loss of blood volume, pooling of blood within the veins reducing adequate return to the heart and/or low effective heart pumping. Low arterial pressure, especially low pulse pressure, is a sign of shock and contributes to and reflects decreased perfusion.

If there is a significant difference in the pressure from one arm to the other, that may indicate a narrowing (for example, due to aortic coarctation, aortic dissection, thrombosis or embolism) of an artery.

Venous pressure
Venous pressure is the vascular pressure in a vein or in the atria of the heart. It is much less than arterial pressure, with common values of 5 mmHg in the right atrium and 8 mmHg in the left atrium. Measurement of pressures in the venous system and the pulmonary vessels plays an important role in intensive care medicine but requires an invasive central venous catheter.

Blood Pressure (third part): Physiology

2008-12-17T06:24:00.000-08:00

The physics of the circulatory system is very complex. That said, there are many physical factors that influence arterial pressure. Each of these may in turn be influenced by physiological factors, such as diet, exercise, disease, drugs or alcohol, obesity, excess weight and so-forth.

Some physical factors are:

* Rate of pumping. In the circulatory system, this rate is called heart rate, the rate at which blood (the fluid) is pumped by the heart. The volume of blood flow from the heart is called the cardiac output which is the heart rate (the rate of contraction) multiplied by the stroke volume (the amount of blood pumped out from the heart with each contraction). The higher the heart rate, the higher the arterial pressure, assuming no reduction in stroke volume.
* Volume of fluid or blood volume, the amount of blood that is present in the body. The more blood present in the body, the higher the rate of blood return to the heart and the resulting cardiac output. There is some relationship between dietary salt intake and increased blood volume, potentially resulting in higher arterial pressure, though this varies with the individual and is highly dependent on autonomic nervous system response.
* Resistance. In the circulatory system, this is the resistance of the blood vessels. The higher the resistance, the higher the arterial pressure upstream from the resistance to blood flow. Resistance is related to vessel radius (the larger the radius, the lower the resistance), vessel length (the longer the vessel, the higher the resistance), as well as the smoothness of the blood vessel walls. Smoothness is reduced by the buildup of fatty deposits on the arterial walls. Substances called vasoconstrictors can reduce the size of blood vessels, thereby increasing blood pressure. Vasodilators (such as nitroglycerin) increase the size of blood vessels, thereby decreasing arterial pressure. Resistance, and its relation to volumetric flow rate (Q) and pressure difference between the two ends of a vessel are described by Poiseuille's Law.
* Viscosity, or thickness of the fluid. If the blood gets thicker, the result is an increase in arterial pressure. Certain medical conditions can change the viscosity of the blood. For instance, low red blood cell concentration, anemia, reduces viscosity, whereas increased red blood cell concentration increases viscosity. Viscosity also increases with blood sugar concentration—visualize pumping syrup. It had been thought that aspirin and related "blood thinner" drugs decreased the viscosity of blood, but studies found[22] that they act by reducing the tendency of the blood to clot instead.

In practice, each individual's autonomic nervous system responds to and regulates all these interacting factors so that, although the above issues are important, the actual arterial pressure response of a given individual varies widely because of both split-second and slow-moving responses of the nervous system and end organs. These responses are very effective in changing the variables and resulting blood pressure from moment to moment.

[edit] Mean arterial pressure

The mean arterial pressure (MAP) is the average over a cardiac cycle and is determined by the cardiac output (CO), systemic vascular resistance (SVR), and central venous pressure (CVP),[23]

\! MAP = (CO \cdot SVR) + CVP

MAP can be approximately determined from measurements of the systolic pressure \! P_{sys} and the diastolic pressure \! P_{dias} while there is a normal resting heart rate,[23]

\! MAP \approxeq P_{dias} + \frac{1}{3} (P_{sys} - P_{dias})

[edit] Pulse pressure

The up and down fluctuation of the arterial pressure results from the pulsatile nature of the cardiac output, i.e. the heartbeat. The pulse pressure is determined by the interaction of the stroke volume of the heart, compliance (ability to expand) of the aorta, and the resistance to flow in the arterial tree. By expanding under pressure, the aorta absorbs some of the force of the blood surge from the heart during a heartbeat. In this way the pulse pressure is reduced from what it would be if the aorta wasn't compliant.[24]

The pulse pressure can be simply calculated from the difference of the measured systolic and diastolic pressures,[24]

\! P_{pulse} = P_{sys} - P_{dias}

[edit] Vascular resistance

The larger arteries, including all large enough to see without magnification, are low resistance conduits (assuming no advanced atherosclerotic changes) with high flow rates that generate only small drops in pressure. For instance, with a subject in the supine position, blood travelling from the heart to the toes typically only experiences a 5 mmHg drop in mean pressure.

[edit] Vascular pressure wave

Modern physiology developed the concept of the vascular pressure wave (VPW). This wave is created by the heart during the systole and originates in the ascending aorta. Much faster than the stream of blood itself, it is then transported through the vessel walls to the peripheral arteries. There the pressure wave can be palpated as the peripheral pulse. As the wave is reflected at the peripheral veins it runs back in a centripetal fashion. Where the crests of the reflected and the original wave meet, the pressure inside the vessel is higher than the true pressure in the aorta. This concept explains why the arterial pressure inside the peripheral arteries of the legs and arms is higher than the arterial pressure in the aorta,[25][26][27] and in turn for the higher pressures seen at the ankle compared to the arm with normal ankle brachial pressure index values.

[edit] Regulation

The endogenous regulation of arterial pressure is not completely understood. Currently, three mechanisms of regulating arterial pressure have been well-characterized:

* Baroreceptor reflex: Baroreceptors detect changes in arterial pressure and send signals ultimately to the medulla of the brain stem. The medulla, by way of the autonomic nervous system, adjusts the mean arterial pressure by altering both the force and speed of the heart's contractions, as well as the total peripheral resistance. The most important arterial baroreceptors are located in the left and right carotid sinuses and in the aortic arch.[28]

* Renin-angiotensin system (RAS): This system is generally known for its long-term adjustment of arterial pressure. This system allows the kidney to compensate for loss in blood volume or drops in arterial pressure by activating an endogenous vasoconstrictor known as angiotensin II.

* Aldosterone release: This steroid hormone is released from the adrenal cortex in response to angiotensin II or high serum potassium levels. Aldosterone stimulates sodium retention and potassium excretion by the kidneys. Since sodium is the main ion that determines the amount of fluid in the blood vessels by osmosis, aldosterone will increase fluid retention, and indirectly, arterial pressure.

These different mechanisms are not necessarily independent of each other, as indicated by the link between the RAS and aldosterone release. Currently, the RAS system is targeted pharmacologically by ACE inhibitors and angiotensin II receptor antagonists. The aldosterone system is directly targeted by spironolactone, an aldosterone antagonist. The fluid retention may be targeted by diuretics; the antihypertensive effect of diuretics is due to its effect on blood volume. Generally, the baroreceptor reflex is not targeted in hypertension because if blocked, individuals may suffer from orthostatic hypotension and fainting.

Blood Pressure (second part): Classification

2008-11-27T08:41:00.000-08:00

Normal values

While average values for arterial pressure could be computed for any given population, there is often a large variation from person to person; arterial pressure also varies in individuals from moment to moment. Additionally, the average of any given population may have a questionable correlation with its general health, thus the relevance of such average values is equally questionable. However, in a study of 100 subjects with no known history of hypertension, an average blood pressure of 112/64 mmHg was found,[15] which is in the normal range.

In children the normal ranges are lower than for adults.[16] In the elderly, blood pressure tends to be higher than normal adult values, largely because of reduced flexibility of the arteries. Factors such as age, gender and race[citation needed] influence blood pressure values. Pressure also varies with exercise, emotional reactions, sleep, digestion and time of day.

Differences between left and right arm blood pressure measurements tend to be random and average to nearly zero if enough measurements are taken. However, in a small percentage of cases there is a consistently present difference greater than 10 mmHg which may need further investigation, e.g. for obstructive arterial disease.[17] [18]

The risk of cardiovascular disease increases progressively throughout the range of higher arterial pressure that begins at 115/75 mmHg.[19] In the past, hypertension was only diagnosed if secondary signs of high arterial pressure were present, along with a prolonged high systolic pressure reading over several visits. In the US, this reactive stance has been soundly rejected in light of recent evidence. However in the UK, patients’ readings are still considered normal up to 140/90 mmHg.[20]

Clinical trials demonstrate that people who maintain arterial pressures at the low end of these pressure ranges have much better long term cardiovascular health. The principal medical debate concerns the aggressiveness and relative value of methods used to lower pressures into this range for those who do not maintain such pressure on their own. Elevations, more commonly seen in older people, though often considered normal, are associated with increased morbidity and mortality. The clear trend from double blind clinical trials (for the better strategies and agents) demonstrates that lower arterial pressure correlates with lower rates of disease.[citation needed]

from wikipedia.org

Blood Pressure (first part): measurament

2008-11-06T13:56:00.000-08:00

Blood pressure
From Wikipedia, the free encyclopedia

Blood pressure refers to the force exerted by circulating blood on the walls of blood vessels, and constitutes one of the principal vital signs. The pressure of the circulating blood decreases as blood moves through arteries, arterioles, capillaries, and veins; the term blood pressure generally refers to arterial pressure, i.e., the pressure in the larger arteries, the blood vessels that take blood away from the heart. Arterial pressure is most commonly measured via a sphygmomanometer, which historically used the height of a column of mercury to reflect the circulating pressure (see Non-invasive measurement). Today blood pressure values are still reported in millimetres of mercury (mmHg), though aneroid and electronic devices do not use mercury.

For each heartbeat, blood pressure varies between systolic and diastolic pressures. Systolic pressure is peak pressure in the arteries, which occurs near the beginning of the cardiac cycle when the ventricles are contracting. Diastolic pressure is minimum pressure in the arteries, which occurs near the end of the cardiac cycle when the ventricles are filled with blood. An example of normal measured values for a resting, healthy adult human is 115 mmHg systolic and 75 mmHg diastolic (written as 115/75 mmHg, and spoken as "one fifteen over seventy-five"). Pulse pressure is the difference between systolic and diastolic pressures.

Systolic and diastolic arterial blood pressures are not static but undergo natural variations from one heartbeat to another and throughout the day (in a circadian rhythm). They also change in response to stress, nutritional factors, drugs, disease, exercise, and momentarily from standing up. Sometimes the variations are large. Hypertension refers to arterial pressure being abnormally high, as opposed to hypotension, when it is abnormally low. Along with body temperature, blood pressure measurements are the most commonly measured physiological parameters.

Measurement

Arterial pressures can be measured invasively (by penetrating the skin and measuring inside the blood vessels) or non-invasively. The former is usually restricted to a hospital setting.

Units
The predominantly used unit for blood pressure measurement is mmHg (millimeter of mercury). Sometimes the unit kPa (kilopascal) is used, where 1 kPa = 7.50 mmHg.

Noninvasive measurement
The noninvasive auscultatory (from the Latin for listening) and oscillometric measurements are simpler and quicker than invasive measurements, require less expertise in fitting, have virtually no complications, and are less unpleasant and painful for the patient. However, non-invasive measures may yield somewhat lower accuracy and small systematic differences in numerical results. Non-invasive measurement methods are more commonly used for routine examinations and monitoring.

Palpation methods
A minimum systolic value can be roughly estimated without any equipment by palpation, most often used in emergency situations. Palpation of a radial pulse indicates a minimum blood pressure of 80 mmHg, a femoral pulse indicates at least 70 mmHg, and a carotid pulse indicates a minimum of 60 mmHg. However, one study indicated that this method was not accurate enough and often overestimated patients' systolic blood pressure.[1] A more accurate value of systolic blood pressure can be obtained with a sphygmomanometer and palpating for when a radial pulse returns.[2] Because a diastolic pressure cannot be obtained by this method, blood pressures obtained by palpation are noted as "/P".[3]

Auscultatory methods
Auscultatory method aneroid sphygmomanometer with stethoscope
Mercury manometer

The auscultatory method uses a stethoscope and a sphygmomanometer. This comprises an inflatable (Riva-Rocci) cuff placed around the upper arm at roughly the same vertical height as the heart, attached to a mercury or aneroid manometer. The mercury manometer, considered to be the gold standard for arterial pressure measurement, measures the height of a column of mercury, giving an absolute result without need for calibration, and consequently not subject to the errors and drift of calibration which affect other methods. The use of mercury manometers is often required in clinical trials and for the clinical measurement of hypertension in high risk patients, such as pregnant women.

A cuff of appropriate size is fitted and inflated manually by repeatedly squeezing a rubber bulb until the artery is completely occluded. Listening with the stethoscope to the brachial artery at the elbow, the examiner slowly releases the pressure in the cuff. When blood just starts to flow in the artery, the turbulent flow creates a "whooshing" or pounding (first Korotkoff sound). The pressure at which this sound is first heard is the systolic blood pressure. The cuff pressure is further released until no sound can be heard (fifth Korotkoff sound), at the diastolic arterial pressure. Sometimes, the pressure is palpated (felt by hand) to get an estimate before auscultation.

Oscillometric methods
Oscillometric methods are sometimes used in the long-term measurement and sometimes in general practice. The equipment is functionally similar to that of the auscultatory method, but with an electronic pressure sensor (transducer) fitted in to detect blood flow, instead of using the stethoscope and the expert's ear. In practice, the pressure sensor is a calibrated electronic device with a numerical readout of blood pressure. To maintain accuracy, calibration must be checked periodically, unlike the inherently accurate mercury manometer. In most cases the cuff is inflated and released by an electrically operated pump and valve, which may be fitted on the wrist (elevated to heart height), although the upper arm is preferred. They vary widely in accuracy, and should be checked at specified intervals and if necessary recalibrated.

Oscillometric measurement requires less skill than the auscultatory technique, and may be suitable for use by untrained staff and for automated patient home monitoring.

The cuff is inflated to a pressure initially in excess of the systolic arterial pressure, and then reduces to below diastolic pressure over a period of about 30 seconds. When blood flow is nil (cuff pressure exceeding systolic pressure) or unimpeded (cuff pressure below diastolic pressure), cuff pressure will be essentially constant. It is essential that the cuff size is correct: undersized cuffs may yield too high a pressure, whereas oversized cuffs yield too low a pressure. When blood flow is present, but restricted, the cuff pressure, which is monitored by the pressure sensor, will vary periodically in synchrony with the cyclic expansion and contraction of the brachial artery, i.e., it will oscillate. The values of systolic and diastolic pressure are computed, not actually measured from the raw data, using an algorithm; the computed results are displayed.

Oscillometric monitors may produce inaccurate readings in patients with heart and circulation problems, that include arterial sclerosis, arrhythmia, preeclampsia, pulsus alternans, and pulsus paradoxus.

In practice the different methods do not give identical results; an algorithm and experimentally obtained coefficients are used to adjust the oscillometric results to give readings which match the auscultatory results as well as possible.[4] Some equipment uses computer-aided analysis of the instantaneous arterial pressure waveform to determine the systolic, mean, and diastolic points. Since many oscillometric devices have not been validated, caution must be given as most are not suitable in clinical and acute care settings.

The term NIBP, for Non-Invasive Blood Pressure, is often used to describe oscillometric monitoring equipment.

Invasive measurement
Arterial blood pressure (BP) is most accurately measured invasively through an arterial line. Invasive arterial pressure measurement with intravascular cannulae involves direct measurement of arterial pressure by placing a cannula needle in an artery (usually radial, femoral, dorsalis pedis or brachial). This is usually done by an anesthesiologist or surgeon in a hospital.

The cannula must be connected to a sterile, fluid-filled system, which is connected to an electronic pressure transducer. The advantage of this system is that pressure is constantly monitored beat-by-beat, and a waveform (a graph of pressure against time) can be displayed. This invasive technique is regularly employed in human and veterinary intensive care medicine, anesthesiology, and for research purposes.

Cannulation for invasive vascular pressure monitoring is infrequently associated with complications such as thrombosis, infection, and bleeding. Patients with invasive arterial monitoring require very close supervision, as there is a danger of severe bleeding if the line becomes disconnected. It is generally reserved for patients where rapid variations in arterial pressure are anticipated.

Invasive vascular pressure monitors are pressure monitoring systems designed to acquire pressure information for display and processing. There are a variety of invasive vascular pressure monitors for trauma, critical care, and operating room applications. These include single pressure, dual pressure, and multi-parameter (i.e. pressure / temperature). The monitors can be used for measurement and follow-up of arterial, central venous, pulmonary arterial, left atrial, right atrial, femoral arterial, umbilical venous, umbilical arterial, and intracranial pressures.

Vascular pressure parameters are derived in the monitor's microcomputer system. Usually, systolic, diastolic, and mean pressures are displayed simultaneously for pulsatile waveforms (i.e. arterial and pulmonary arterial). Some monitors also calculate and display CPP (cerebral perfusion pressure). Normally, a zero key on the front of the monitor makes pressure zeroing extremely fast and easy. Alarm limits may be set to assist the medical professional responsible for observing the patient. High and low alarms may be set on displayed temperature parameters.

Home monitoring
For some patients, blood pressure measurements taken in a doctor's office may not correctly characterize their typical blood pressure. In up to 25% of patients, the office visit blood pressure reading is higher than their typical blood pressure. This type of error is called white coat hypertension and can result from anxiety related to an examination by a health care professional.[5] The misdiagnosis of hypertension for these patients can result in needless and possibly harmful medication. On the other hand, in some cases a lower than typical blood pressure reading occurs at the doctor's office and these patients may fail to get needed treatment for hypertension.[6] Ambulatory blood pressure devices that take readings every half hour throughout the day and night have been used for identifying and mitigating these problems. Except for periods during sleep, home monitoring could be used for these purposes instead of ambulatory blood pressure monitoring.[7] Home monitoring may also be used to improve hypertension management and to monitor the effects of lifestyle changes and medication related to blood pressure.[8] Compared to ambulatory blood pressure measurements, home monitoring has been found to be an effective and lower cost alternative.

Aside from the white coat effect, arterial pressure readings outside of a clinical setting are usually slightly lower in the majority of people. The studies that looked into the risks from hypertension and the benefits of lowering the arterial pressure in affected patients were based on readings in a clinical environment.

When measuring blood pressure, an accurate reading requires that one not drink coffee, smoke cigarettes, or engage in strenuous exercise for 30 minutes before taking the reading. A full bladder may have a small effect on blood pressure readings, so if the urge to urinate exists, one should do so before the reading. For 5 minutes before the reading, one should sit upright in a chair with his or her feet flat on the floor and without any limbs crossed. The blood pressure cuff should always be against bare skin, as readings taken over a shirt sleeve are less accurate. During the reading, the arm that is used should be relaxed and kept at heart level, for example by resting it on a table.[11]

Since arterial pressure varies throughout the day, measurements intended to monitor changes over longer time frames should be taken at the same time of day to ensure that the readings taken are comparable. Suitable times are:

* immediately after awakening (before washing/dressing and taking breakfast/drink), while the body is still resting,
* immediately after finishing work.

Automatic self-contained blood pressure monitors are available at reasonable prices, some of which are capable of Korotkoff's measurement in addition to oscillometric methods, enabling irregular heartbeat patients to accurately measure their blood pressure at home, which was not possible using the traditional devices.[citation needed]

Those using home arterial pressure monitoring devices are increasingly also making use of arterial pressure charting software.[12] These charting methods provide print outs for the patients physician and reminders on how often to check arterial pressure.

cancer (last part): Epidemiology, History and Research

2008-10-16T10:33:00.000-07:00

Epidemiology
Cancer epidemiology is the study of the incidence of cancer as a way to infer possible trends and causes. The first such cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that cancer of the scrotum was a common disease among chimney sweeps. The work of other individual physicians led to various insights, but when physicians started working together they could make firmer conclusions.
A founding paper of this discipline was the work of Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health. Her ground-breaking work on cancer epidemiology was carried on by Richard Doll and Austin Bradford Hill, who published "Lung Cancer and Other Causes of Death In Relation to Smoking. A Second Report on the Mortality of British Doctors" followed in 1956 (otherwise known as the British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large amounts of cancer data. Modern epidemiological methods are closely linked to current concepts of disease and public health policy. Over the past 50 years, great efforts have been spent on gathering data across medical practise, hospital, provincial, state, and even country boundaries, as a way to study the interdependence of environmental and cultural factors on cancer incidence.
Cancer epidemiology must contend with problems of lead time bias and length time bias. Lead time bias is the concept that early diagnosis may artificially inflate the survival statistics of a cancer, without really improving the natural history of the disease. Length bias is the concept that slower growing, more indolent tumors are more likely to be diagnosed by screening tests, but improvements in diagnosing more cases of indolent cancer may not translate into better patient outcomes after the implementation of screening programs. A similar epidemiological concern is overdiagnosis, the tendency of screening tests to diagnose diseases that may not actually impact the patient's longevity. This problem especially applies to prostate cancer and PSA screening.[87]
Some cancer researchers have argued that negative cancer clinical trials lack sufficient statistical power to discover a benefit to treatment. This may be due to fewer patients enrolled in the study than originally planned.[88]
State and regional cancer registries are organizations that abstract clinical data about cancer from patient medical records. These institutions provide information to state and national public health groups to help track trends in cancer diagnosis and treatment. One of the largest and most important cancer registries is SEER, administered by the US Federal government.[89] Health information privacy concerns have led to the restricted use of cancer registry data in the United States Department of Veterans Affairs[90][91][92] and other institutions.[93]
In some Western countries, such as the USA,[4] and the UK[94] cancer is overtaking cardiovascular disease as the leading cause of death. In many Third World countries cancer incidence (insofar as this can be measured) appears much lower, most likely because of the higher death rates due to infectious disease or injury. With the increased control over malaria and tuberculosis in some Third World countries, incidence of cancer is expected to rise; this is termed the epidemiologic transition in epidemiological terminology.
Cancer epidemiology closely mirrors risk factor spread in various countries. Hepatocellular carcinoma (liver cancer) is rare in the West but is the main cancer in China and neighbouring countries, most likely due to the endemic presence of hepatitis B and aflatoxin in that population. Similarly, with tobacco smoking becoming more common in various Third World countries, lung cancer incidence has increased in a parallel fashion.

History
Today, the Greek term carcinoma is the medical term for a malignant tumor derived from epithelial cells. It is Celsus who translated carcinos into the Latin cancer, also meaning crab. Galen used "oncos" to describe all tumours, the root for the modern word oncology.[95]
Hippocrates described several kinds of cancers. He called benign tumours oncos, Greek for swelling, and malignant tumours carcinos, Greek for crab or crayfish. This name comes from the appearance of the cut surface of a solid malignant tumour, with the veins stretched on all sides as the animal the crab has its feet, whence it derives its name[96] (see picture). He later added the suffix -oma, Greek for swelling, giving the name carcinoma. Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatment was based on the humor theory of four bodily fluids (black and yellow bile, blood, and phlegm). According to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remained popular until the 19th century with the discovery of cells.
Our oldest description and surgical treatment of cancer was discovered in Egypt and dates back to approximately 1600 B.C. The Papyrus describes 8 cases of ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."[97]
Another very early surgical treatment for cancer was described in the 1020s by Avicenna (Ibn Sina) in The Canon of Medicine. He stated that the excision should be radical and that all diseased tissue should be removed, which included the use of amputation or the removal of veins running in the direction of the tumor. He also recommended the use of cauterization for the area being treated if necessary.[98]
In the 16th and 17th centuries, it became more acceptable for doctors to dissect bodies to discover the cause of death. The German professor Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor Francois de la Boe Sylvius, a follower of Descartes, believed that all disease was the outcome of chemical processes, and that acidic lymph fluid was the cause of cancer. His contemporary Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was contagious.[99]
With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("metastasis"). This view of the disease was first formulated by the English surgeon Campbell De Morgan between 1871 and 1874.[100] The use of surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, asepsis improved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late 1800s felt that the rate of cure after surgery had been higher before asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor. During the same period, the idea that the body was made up of varous tissues, that in turn were made up of millions of cells, laid rest the humor-theories about chemical imbalances in the body. The age of cellular pathology was born.
When Marie Curie and Pierre Curie discovered radiation at the end of the 19th century, they stumbled upon the first effective non-surgical cancer treatment. With radiation came also the first signs of multi-disciplinary approaches to cancer treatment. The surgeon was no longer operating in isolation, but worked together with hospital radiologists to help patients. The complications in communication this brought, along with the necessity of the patient's treatment in a hospital facility rather than at home, also created a parallel process of compiling patient data into hospital files, which in turn led to the first statistical patient studies.
Cancer patient treatment and studies were restricted to individual physicians' practices until World War II, when medical research centers discovered that there were large international differences in disease incidence. This insight drove national public health bodies to make it possible to compile health data across practises and hospitals, a process that many countries do today. The Japanese medical community observed that the bone marrow of bomb victims in Hiroshima and Nagasaki was completely destroyed. They concluded that diseased bone marrow could also be destroyed with radiation, and this led to the discovery of bone marrow transplants for leukemia. Since WWII, trends in cancer treatment are to improve on a micro-level the existing treatment methods, standardize them, and globalize them as a way to find cures through epidemiology and international partnerships.

Research
Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. The improved understanding of molecular biology and cellular biology due to cancer research has led to a number of new, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971. Since 1971 the United States has invested over $200 billion on cancer research, that total includes money invested by public and private sectors and foundations.[101]

from wikipedia.org

cancer (five part):vaccination and screening

2008-09-16T13:08:00.000-07:00

Prevention
Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of pre-malignant lesions). The epidemiological concept of "prevention" is usually defined as either primary prevention, for people who have not been diagnosed with a particular disease, or secondary prevention, aimed at reducing recurrence or complications of a previously diagnosed illness.
Observational epidemiological studies that show associations between risk factors and specific cancers mostly serve to generate hypotheses about potential interventions that could reduce cancer incidence or morbidity. Randomized controlled trials then test whether hypotheses generated by epidemiological trials and laboratory research actually result in reduced cancer incidence and mortality. In many cases, findings from observational epidemiological studies are not confirmed by randomized controlled trials.
About a third of the twelve most common cancers worldwide are due to nine potentially modifiable risk factors. Men with cancer are twice as likely as women to have a modifiable risk factor for their disease. The nine risk factors are tobacco smoking, excessive alcohol use, diet low in fruit and vegetables, limited physical exercise, human papillomavirus infection (unsafe sex), urban air pollution, domestic use of solid fuels, and contaminated injections (hepatitis B and C).[34]

Modifiable ("lifestyle") risk factors
Examples of modifiable cancer risk factors include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men[35]), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexually transmitted diseases, the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, and certain occupational and chemical exposures.
Every year, at least 200,000 people die worldwide from cancer related to their workplace.[36] Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco smoke, or leukemia from exposure to benzene at their workplaces.[36] Currently, most cancer deaths caused by occupational risk factors occur in the developed world.[36] It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation.[37]
See alcohol and cancer for more on that topic.

Diet
The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States). Studies have shown that immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.[38] Whether reducing obesity in a population also reduces cancer incidence is unknown.
Despite frequent reports of particular substances (including foods) having a beneficial or detrimental effect on cancer risk, few of these have an established link to cancer. These reports are often based on studies in cultured cell media or animals. Public health recommendations cannot be made on the basis of these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.
Proposed dietary interventions for primary cancer risk reduction generally gain support from epidemiological association studies. Examples of such studies include reports that reduced meat consumption is associated with decreased risk of colon cancer,[39] and reports that consumption of coffee is associated with a reduced risk of liver cancer.[40] Studies have linked consumption of grilled meat to an increased risk of stomach cancer,[41] colon cancer,[42] breast cancer,[43] and pancreatic cancer,[44] a phenomenon which could be due to the presence of carcinogens such as benzopyrene in foods cooked at high temperatures.
A 2005 secondary prevention study showed that consumption of a plant-based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time.[45] These results were amplified by a 2006 study in which over 2,400 women were studied, half randomly assigned to a normal diet, the other half assigned to a diet containing less than 20% calories from fat. The women on the low fat diet were found to have a markedly lower risk of breast cancer recurrence, in the interim report of December, 2006.[46]
Recent studies have also demonstrated potential links between some forms of cancer and high consumption of refined sugars and other simple carbohydrates.[47][48][49][50][51] Although the degree of correlation and the degree of causality is still debated,[52][53][54] some organizations have in fact begun to recommend reducing intake of refined sugars and starches as part of their cancer prevention regimens.
In November 2007, the American Institute for Cancer Research (AICR), in conjunction with the World Cancer Research Fund (WCRF), published Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective', "the most current and comprehensive analysis of the literature on diet, physical activity and cancer".[59] The WCRF/AICR Expert Report lists 10 recommendations that people can follow to help reduce their risk of developing cancer, including the following dietary guidelines: (1) reducing intake of foods and drinks that promote weight gain, namely energy-dense foods and sugary drinks, (2) eating mostly foods of plant origin, (3) limiting intake of red meat and avoiding processed meat, (4) limiting consumption of alcoholic beverages, and (5) reducing intake of salt and avoiding mouldy cereals (grains) or pulses (legumes).[60][61]

Vitamins
The idea that cancer can be prevented through vitamin supplementation stems from early observations correlating human disease with vitamin deficiency, such as pernicious anemia with vitamin B12 deficiency, and scurvy with Vitamin C deficiency. This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer. The cancer-fighting components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly being advised to consume fresh, unprocessed fruits and vegetables for maximal health benefits.[62]
Epidemiological studies have shown that low vitamin D status is correlated to increased cancer risk.[63][64] However, the results of such studies need to be treated with caution, as they cannot show whether a correlation between two factors means that one causes the other (i.e. correlation does not imply causation).[65] The possibility that Vitamin D might protect against cancer has been contrasted with the risk of malignancy from sun exposure. Since exposure to the sun enhances natural human production of vitamin D, some cancer researchers have argued that the potential deleterious malignant effects of sun exposure are far outweighed by the cancer-preventing effects of extra vitamin D synthesis in sun-exposed skin. In 2002, Dr. William B. Grant claimed that 23,800 premature cancer deaths occur in the US annually due to insufficient UVB exposure (apparently via vitamin D deficiency).[66] This is higher than 8,800 deaths occurred from melanoma or squamous cell carcinoma, so the overall effect of sun exposure might be beneficial. Another research group[67][68] estimates that 50,000–63,000 individuals in the United States and 19,000 - 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D.
The case of beta-carotene provides an example of the importance of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in lung cancer. This hypothesis led to a series of large randomized clinical trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but not significantly, increased by beta-carotene, leading to an early termination of the study.[69]
Results reported in the Journal of the American Medical Association (JAMA) in 2007 indicate that folic acid supplementation is not effective in preventing colon cancer, and folate consumers may be more likely to form colon polyps.[70]

Chemoprevention
The neutrality of this section is disputed.
Please see the discussion on the talk page. (June 2008)
Please do not remove this message until the dispute is resolved.
The concept that medications could be used to prevent cancer is an attractive one, and many high-quality clinical trials support the use of such chemoprevention in defined circumstances.
Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile.[71]
Raloxifene is a SERM like tamoxifen; it has been shown (in the STAR trial) to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, raloxifene had fewer side effects than tamoxifen, though it did permit more DCIS to form.[71]
Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors.[72] The effect of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients[73] and in the general population.[74][75] In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity.

Vaccination
Considerable[weasel words] research effort is now devoted to the development of vaccines to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific epitopes) and to potential venues for gene therapy for individuals with genetic mutations or polymorphisms that put them at high risk of cancer.
As reported above, a preventive human papillomavirus vaccine exists that targets certain sexually transmitted strains of human papillomavirus that are associated with the development of cervical cancer and genital warts. The only two HPV vaccines on the market as of October 2007 are Gardasil and Cervarix.

Screening
Cancer screening is an attempt to detect unsuspected cancers in an asymptomatic population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.
Screening for cancer can lead to earlier diagnosis in specific cases. Early diagnosis may lead to extended life, but may also falsely prolong the lead time to death through lead time bias or length time bias.
A number of different screening tests have been developed for different malignancies. Breast cancer screening can be done by breast self-examination, though this approach was discredited by a 2005 study in over 300,000 Chinese women. Screening for breast cancer with mammograms has been shown to reduce the average stage of diagnosis of breast cancer in a population. Stage of diagnosis in a country has been shown to decrease within ten years of introduction of mammographic screening programs. Colorectal cancer can be detected through fecal occult blood testing and colonoscopy, which reduces both colon cancer incidence and mortality, presumably through the detection and removal of pre-malignant polyps. Similarly, cervical cytology testing (using the Pap smear) leads to the identification and excision of precancerous lesions. Over time, such testing has been followed by a dramatic reduction of cervical cancer incidence and mortality. Testicular self-examination is recommended for men beginning at the age of 15 years to detect testicular cancer. Prostate cancer can be screened using a digital rectal exam along with prostate specific antigen (PSA) blood testing, though some authorities (such as the US Preventive Services Task Force) recommend against routinely screening all men.
Screening for cancer is controversial in cases when it is not yet known if the test actually saves lives. The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments. For example: when screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to treatment. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation. Follow up procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). Similarly, for breast cancer, there have recently been criticisms that breast screening programs in some countries cause more problems than they solve. This is because screening of women in the general population will result in a large number of women with false positive results which require extensive follow-up investigations to exclude cancer, leading to having a high number-to-treat (or number-to-screen) to prevent or catch a single case of breast cancer early.
Cervical cancer screening via the Pap smear has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being largely caused by a virus, it has clear risk factors (sexual contact), and the natural progression of cervical cancer is that it normally spreads slowly over a number of years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.
For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake cancer screening.
Use of medical imaging to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an incidentaloma - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations. Recent studies of CT scan-based screening for lung cancer in smokers have had equivocal results, and systematic screening is not recommended as of July 2007. Randomized clinical trials of plain-film chest X-rays to screen for lung cancer in smokers have shown no benefit for this approach.
Canine cancer detection has shown promise, but is still in the early stages of research.

cancer (fourth part) : prognosis

2008-08-19T04:08:00.000-07:00

Cancer has a reputation for being a deadly disease. While this certainly applies to certain particular types, the truths behind the historical connotations of cancer are increasingly being overturned by advances in medical care. Some types of cancer have a prognosis that is substantially better than nonmalignant diseases such as heart failure and stroke.
Progressive and disseminated malignant disease has a substantial impact on a cancer patient's quality of life, and many cancer treatments (such as chemotherapy) may have severe side-effects. In the advanced stages of cancer, many patients need extensive care, affecting family members and friends. Palliative care solutions may include permanent or "respite" hospice nursing.

Emotional impact
Many local organizations offer a variety of practical and support services to people with cancer. Support can take the form of support groups, counseling, advice, financial assistance, transportation to and from treatment, films or information about cancer. Neighborhood organizations, local health care providers, or area hospitals may have resources or services available.
Counseling can provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, peer counseling, bereavement, patient-to-patient, and sexuality.
Many governmental and charitable organizations have been established to help patients cope with cancer. These organizations often are involved in cancer prevention, cancer treatment, and cancer research.

Causes
Main article: Carcinogenesis
Cancer is a diverse class of diseases which differ widely in their causes and biology. The common thread in all known cancers is the acquisition of abnormalities in the genetic material of the cancer cell and its progeny. Research into the pathogenesis of cancer can be divided into three broad areas of focus. The first area of research focuses on the agents and events which cause or facilitate genetic changes in cells destined to become cancer. Second, it is important to uncover the precise nature of the genetic damage, and the genes which are affected by it. The third focus is on the consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events, leading to further progression of the cancer.

Chemical carcinogens
Cancer pathogenesis is traceable back to DNA mutations that impact cell growth and metastasis. Substances that cause DNA mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. Tobacco smoking is associated with lung cancer and bladder cancer. Prolonged exposure to asbestos fibers is associated with mesothelioma.
Many mutagens are also carcinogens, but some carcinogens are not mutagens. Alcohol is an example of a chemical carcinogen that is not a mutagen. Such chemicals are thought to promote cancers through their stimulating effect on the rate of cell mitosis. Faster rates of mitosis leaves less time for repair enzymes to repair damaged DNA during DNA replication, increasing the likelihood of a genetic mistake. A mistake made during mitosis can lead to the daughter cells receiving the wrong number of chromosomes (see aneuploidy above).
Decades of research have demonstrated the strong association between tobacco use and cancers of many sites, making it perhaps the most important human carcinogen. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men.

Ionizing radiation
Sources of ionizing radiation, such as radon gas, can cause cancer. Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies.
Radiation from mobile phones has been conjectured for some time as a cause but this theory has not gained mainstream support. Nevertheless some experts caution against prolonged exposure.[14]

Infectious diseases
Some cancers can be caused by infection with pathogens.[15] Many cancers originate from a viral infection; this is especially true in animals such as birds, but also in humans, as viruses are responsible for 15% of human cancers worldwide. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage.[16] The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely transforming viruses, the virus carries an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, the virus genome is inserts near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements then cause overexpression of that proto-oncogene. This induces uncontrolled cell division. Because the site of insertion is not specific to proto-oncogenes and the chance of insertion near any proto-oncogene is low, slowly-transforming viruses will cause tumors much longer after infection than the acutely-transforming viruses.
Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer in 0.47% of hepatitis B patients per year (especially in Asia, less so in North America), and in 1.4% of hepatitis C carriers per year. Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development. Worldwide, liver cancer is one of the most common, and most deadly, cancers due to a huge burden of viral hepatitis transmission and disease.
Advances in cancer research have made a vaccine designed to prevent cancer available. In 2006, the US FDA approved a human papilloma virus vaccine, called Gardasil. The vaccine protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. In March 2007, the US CDC Advisory Committee on Immunization Practices (ACIP) officially recommended that females aged 11-12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization.
In addition to viruses, researchers have noted a connection between bacteria and certain cancers. The most prominent example is the link between chronic infection of the wall of the stomach with Helicobacter pylori and gastric cancer.[17][18] Although only a minority of those infected with Helicobacter go on to develop cancer, since this pathogen is quite common it is probably responsible for the majority of these cancers.[19]

Hormonal imbalances
Some hormones can act in a similar manner to non-mutagenic carcinogens in that they may stimulate excessive cell growth. A well-established example is the role of hyperestrogenic states in promoting endometrial cancer.

Immune system dysfunction
HIV is associated with a number of malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma, and HPV-associated malignancies such as anal cancer and cervical cancer. AIDS-defining illnesses have long included these diagnoses. The increased incidence of malignancies in HIV patients points to the breakdown of immune surveillance as a possible etiology of cancer.[20] Certain other immune deficiency states (e.g. common variable immunodeficiency and IgA deficiency) are also associated with increased risk of malignancy.[21]

Heredity
Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component, often a defective tumor suppressor allele. Famous examples are:

* certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer
* tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)
* Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft tissue sarcoma, brain tumors) due to mutations of p53
* Turcot syndrome (brain tumors and colonic polyposis)
* Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
* Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome) can include familial cases of colon cancer, uterine cancer, gastric cancer, and ovarian cancer, without a preponderance of colon polyps.
* Retinoblastoma, when occurring in young children, is due to a hereditary mutation in the retinoblastoma gene.
* Down syndrome patients, who have an extra chromosome 21, are known to develop malignancies such as leukemia and testicular cancer, though the reasons for this difference are not well understood.

Other causes
A few types of cancer in non-humans have been found to be caused by the tumor cells themselves. This phenomenon is seen in dogs with Sticker's sarcoma, also known as canine transmissible venereal tumor[22], as well as Devil facial tumour disease in Tasmanian devils. The closest known analogue to this in humans is individuals who have developed cancer from tumors hiding inside organ transplants.

Pathophysiology
Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, genes which regulate cell growth and differentiation must be altered. Genetic changes can occur at many levels, from gain or loss of entire chromosomes to a mutation affecting a single DNA nucleotide. There are two broad categories of genes which are affected by these changes. Oncogenes may be normal genes which are expressed at inappropriately high levels, or altered genes which have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. Tumor suppressor genes are genes which inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.
There is a diverse classification scheme for the various genomic changes which may contribute to the generation of cancer cells. Most of these changes are mutations, or changes in the nucleotide sequence of genomic DNA. Aneuploidy, the presence of an abnormal number of chromosomes, is one genomic change which is not a mutation, and may involve either gain or loss of one or more chromosomes through errors in mitosis.
Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.
Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.

Epigenetics
Epigenetics is the study of the regulation of gene expression through chemical, non-mutational changes in DNA structure. The theory of epigenetics in cancer pathogenesis is that non-mutational changes to DNA can lead to alterations in gene expression. Normally, oncogenes are silent, for example, because of DNA methylation. Loss of that methylation can induce the aberrant expression of oncogenes, leading to cancer pathogenesis. Known mechanisms of epigenetic change include DNA methylation, and methylation or acetylation of histone proteins bound to chromosomal DNA at specific locations. Classes of medications, known as HDAC inhibitors and DNA methyltransferase inhibitors, can re-regulate the epigenetic signaling in the cancer cell.

Oncogenes
Oncogenes promote cell growth through a variety of ways. Many can produce hormones, a "chemical messenger" between cells which encourage mitosis, the effect of which depends on the signal transduction of the receiving tissue or cells. In other words, when a hormone receptor on a recipient cell is stimulated, the signal is conducted from the surface of the cell to the cell nucleus to effect some change in gene transcription regulation at the nuclear level. Some oncogenes are part of the signal transduction system itself, or the signal receptors in cells and tissues themselves, thus controlling the sensitivity to such hormones. Oncogenes often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and enzymes responsible for producing the products and biochemicals cells use and interact with.
Mutations in proto-oncogenes, which are the normally quiescent counterparts of oncogenes, can modify their expression and function, increasing the amount or activity of the product protein. When this happens, the proto-oncogenes become oncogenes, and this transition upsets the normal balance of cell cycle regulation in the cell, making uncontrolled growth possible. The chance of cancer cannot be reduced by removing proto-oncogenes from the genome, even if this were possible, as they are critical for growth, repair and homeostasis of the organism. It is only when they become mutated that the signals for growth become excessive.
One of the first oncogenes to be defined in cancer research is the ras oncogene. Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumours.[23] Ras was originally identified in the Harvey sarcoma virus genome, and researchers were surprised that not only was this gene present in the human genome but that, when ligated to a stimulating control element, could induce cancers in cell line cultures.[24]

Tumor suppressor genes
Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally, tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of the cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. The p53 protein, one of the most important studied tumor suppressor genes, is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage.
Despite nearly half of all cancers possibly involving alterations in p53, its tumor suppressor function is poorly understood. p53 clearly has two functions: one a nuclear role as a transcription factor, and the other a cytoplasmic role in regulating the cell cycle, cell division, and apoptosis.
The Warburg hypothesis is the preferential use of glycolysis for energy to sustain cancer growth. p53 has been shown to regulate the shift from the respiratory to the glycolytic pathway.[25]
However, a mutation can damage the tumor suppressor gene itself, or the signal pathway which activates it, "switching it off". The invariable consequence of this is that DNA repair is hindered or inhibited: DNA damage accumulates without repair, inevitably leading to cancer.
Mutations of tumor suppressor genes that occur in germline cells are passed along to offspring, and increase the likelihood for cancer diagnoses in subsequent generations. Members of these families have increased incidence and decreased latency of multiple tumors. The tumor types are typical for each type of tumor suppressor gene mutation, with some mutations causing particular cancers, and other mutations causing others. The mode of inheritance of mutant tumor suppressors is that an affected member inherits a defective copy from one parent, and a normal copy from the other. For instance, individuals who inherit one mutant p53 allele (and are therefore heterozygous for mutated p53) can develop melanomas and pancreatic cancer, known as Li-Fraumeni syndrome. Other inherited tumor suppressor gene syndromes include Rb mutations, linked to retinoblastoma, and APC gene mutations, linked to adenopolyposis colon cancer. Adenopolyposis colon cancer is associated with thousands of polyps in colon while young, leading to colon cancer at a relatively early age. Finally, inherited mutations in BRCA1 and BRCA2 lead to early onset of breast cancer.
Development of cancer was proposed in 1971 to depend on at least two mutational events. In what became known as the Knudson two-hit hypothesis, an inherited, germ-line mutation in a tumor suppressor gene would only cause cancer if another mutation event occurred later in the organism's life, inactivating the other allele of that tumor suppressor gene.[26]
Usually, oncogenes are dominant, as they contain gain-of-function mutations, while mutated tumor suppressors are recessive, as they contain loss-of-function mutations. Each cell has two copies of the same gene, one from each parent, and under most cases gain of function mutations in just one copy of a particular proto-oncogene is enough to make that gene a true oncogene. On the other hand, loss of function mutations need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one mutated copy of a tumor suppressor gene can render the other, wild-type copy non-functional. This phenomenon is called the dominant negative effect and is observed in many p53 mutations.
Knudson’s two hit model has recently been challenged by several investigators. Inactivation of one allele of some tumor suppressor genes is sufficient to cause tumors. This phenomenon is called haploinsufficiency and has been demonstrated by a number of experimental approaches. Tumors caused by haploinsufficiency usually have a later age of onset when compared with those by a two hit process.[27]

Cancer cell biology
Often, the multiple genetic changes which result in cancer may take many years to accumulate. During this time, the biological behavior of the pre-malignant cells slowly change from the properties of normal cells to cancer-like properties. Pre-malignant tissue can have a distinctive appearance under the microscope. Among the distinguishing traits are an increased number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, and loss of normal tissue organization. Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure in pre-malignant cells. These early neoplastic changes must be distinguished from hyperplasia, a reversible increase in cell division caused by an external stimulus, such as a hormonal imbalance or chronic irritation.
The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and has not shown invasion into other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.

Clonal evolution
Main article: Somatic evolution in cancer
The process by which normal tissue becomes malignant is a process of somatic evolution within the body[28]. Millions of years of biological evolution insure that the cellular metabolic changes that enable cancer to grow occur only very rarely. Most changes in cellular metabolism that allow cells to grow in a disorderly fashion lead to cell death. Cancer cells undergo a process of natural selection, in that the few cells with new genetic changes that enhance their survival or reproduction continue to multiply, and soon come to dominate the growing tumor, as cells with less favorable genetic change are out-competed[29]. This process is called clonal evolution. Tumors often continue to evolve in response to chemotherapy treatments, and on occasion aberrant cells may acquire resistance to particular anti-cancer pharmaceuticals.

Biological properties of cancer cells
In a 2000 article by Hanahan and Weinberg, the biological properties of malignant tumor cells were summarized as follows:[30]

* Acquisition of self-sufficiency in growth signals, leading to unchecked growth.
* Loss of sensitivity to anti-growth signals, also leading to unchecked growth.
* Loss of capacity for apoptosis, in order to allow growth despite genetic errors and external anti-growth signals.
* Loss of capacity for senescence, leading to limitless replicative potential (immortality)
* Acquisition of sustained angiogenesis, allowing the tumor to grow beyond the limitations of passive nutrient diffusion.
* Acquisition of ability to invade neighbouring tissues, the defining property of invasive carcinoma.
* Acquisition of ability to build metastases at distant sites, the classical property of malignant tumors (carcinomas or others).

The completion of these multiple steps would be a very rare event without :

* Loss of capacity to repair genetic errors, leading to an increased mutation rate (genomic instability), thus accelerating all the other changes.

These biological changes are classical in carcinomas; other malignant tumor may not need all to achieve them all. For example, tissue invasion and displacement to distant sites are normal properties of leukocytes; these steps are not needed in the development of Leukemia. The different steps do not necessarily represent individual mutations. For example, inactivation of a single gene, coding for the P53 protein, will cause genomic instability, evasion of apoptosis and increased angiogenesis.

from wikipedia.org

cancer (third part): cancer therapies

2008-08-02T01:53:00.000-07:00

Diagnosis
Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician (medical doctor) who specializes in the diagnosis of cancer and other diseases.

Investigation
People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

Biopsy
A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.
The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about future behavior of the cancer (prognosis) and best treatment.

Treatment
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A number of experimental cancer treatments are also under development.
Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.
Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.

Surgery
In theory, non-hematological cancers can be cured if entirely removed by surgery, but this is not always possible. When the cancer has metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.
Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.
In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy.
Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Radiation therapy
Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via external beam radiotherapy (EBRT) or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.
Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Chemotherapy
Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.
Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.
The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous stem cell transplantation. Alternatively, hematopoietic stem cells may be transplanted from a matched unrelated donor (MUD).

Targeted therapies
Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib and gefitinib.
Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies.
Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to this peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.
Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors.

Immunotherapy
Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumours include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Vaccines to generate specific immune responses are the subject of intensive research for a number of tumours, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells.
Allogeneic hematopoietic stem cell transplantation ("bone marrow transplantation" from a genetically non-identical donor) can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.

Hormonal therapy
The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Removing or blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial.

Angiogenesis inhibitors
Angiogenesis inhibitors prevent the extensive growth of blood vessels (angiogenesis) that tumors require to survive. Some, such as bevacizumab, have been approved and are in clinical use. One of the main problems with anti-angiogenesis drugs is that many factors stimulate blood vessel growth, in normal cells and cancer. Anti-angiogenesis drugs only target one factor, so the other factors continue to stimulate blood vessel growth. Other problems include route of administration, maintenance of stability and activity and targeting at the tumor vasculature.

Symptom control
Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. Although doctors generally have the therapeutic skills to reduce pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of palliative care has arisen specifically in response to the symptom control needs of this group of patients.
Pain medication, such as morphine and oxycodone, and antiemetics, drugs to suppress nausea and vomiting, are very commonly used in patients with cancer-related symptoms. Improved antiemetics such as ondansetron and analogues, as well as aprepitant have made aggressive treatments much more feasible in cancer patients.
Chronic pain due to cancer is almost always associated with continuing tissue damage due to the disease process or the treatment (i.e. surgery, radiation, chemotherapy). Although there is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, these are not usually the predominant etiologic factors in patients with cancer pain. Furthermore, many patients with severe pain associated with cancer are nearing the end of their lives and palliative therapies are required. Issues such as social stigma of using opioids, work and functional status, and health care consumption are not likely to be important in the overall case management. Hence, the typical strategy for cancer pain management is to get the patient as comfortable as possible using opioids and other medications, surgery, and physical measures. Doctors have been reluctant to prescribe narcotics for pain in terminal cancer patients, for fear of contributing to addiction or suppressing respiratory function. The palliative care movement, a more recent offshoot of the hospice movement, has engendered more widespread support for preemptive pain treatment for cancer patients.
Fatigue is a very common problem for cancer patients, and has only recently become important enough for oncologists to suggest treatment, even though it plays a significant role in many patients' quality of life.

Treatment trials
Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.
A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.
Patients who take part may be helped personally by the treatment they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. At the same time, new treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit. There is no guarantee that a new treatment being tested or a standard treatment will produce good results. In children with cancer, a survey of trials found that those enrolled in trials were on average not more likely to do better or worse than those on standard treatment; this confirms that success or failure of an experimental treatment cannot be predicted.

Complementary and alternative
Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine. "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. CAM use is common among people with cancer; a 2000 study found that 69% cancer patients had used at least one CAM therapy as part of their cancer treatment. Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments which have been investigated and shown to be ineffective continue to be marketed and promoted.

from www.wikipedia.org

cancer (second part):signs and symptoms

2008-07-21T07:58:00.000-07:00

Adult cancers
In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.[4] On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and may vary substantially in other countries:

Child cancers
Cancer can also occur in young children and adolescents, but it is rare (about 150 cases per million yearly in the US). Statistics from the SEER program of the US NCI demonstrate that childhood cancers increased 19% between 1975 and 1990, mainly due to an increased incidence in acute leukemia. Since 1990, incidence rates have decreased.[5]
There is a reasonable doubt that children living near nuclear facilities face an increased risk of cancer.

Infant cancers
The age of peak incidence of cancer in children occurs during the first year of life, in infants. The average annual incidence in the United States, 1975-1995, was 233 per million infants.[5] Several estimates of incidence exist. According to SEER,[5] in the United States:
* Neuroblastoma comprised 28% of infant cancer cases and was the most common malignancy among these young children (65 per million infants).
* The leukemias as a group (41 per million infants) represented the next most common type of cancer, comprising 17% of all cases.
* Central nervous system malignancies comprised 13% of infant cancer, with an average annual incidence rate of nearly 30 per million infants.
* The average annual incidence rates for malignant germ cell and malignant soft tissue tumors were essentially the same at 15 per million infants. Each comprised about 6% of infant cancer.
According to another study:
* Leukemia (usually ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma.
Teratoma (a germ cell tumor) often is cited as the most common tumor in this age group, but most teratomas are surgically removed while still benign, hence not necessarily cancer. Benign teratomas are not reportable to SEER.[citation needed] Prior to the widespread routine use of prenatal ultrasound examinations, the incidence of sacrococcygeal teratomas diagnosed at birth was 25 to 29 per million births.
Female and male infants have essentially the same overall cancer incidence rates, a notable difference compared to older children.
White infants have higher cancer rates than black infants. Leukemias accounted for a substantial proportion of this difference: the average annual rate for white infants (48.7 per million) was 66% higher than for black infants (29.4 per million).[5]
Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.

Signs and symptoms
Roughly, cancer symptoms can be divided into three groups:
* Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice (yellowing the eyes and skin).
* Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.
* Systemic symptoms: weight loss, poor appetite, fatigue and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.
Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

cancer (first part: classification)

2008-07-16T06:34:00.000-07:00

Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age.[1] Cancer causes about 13% of all deaths.[2] According to the American Cancer Society, 7.6 million people died from cancer in the world during 2007.[3] Cancers can affect all animals.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers are usually affected by complex interactions between carcinogens and the host's genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly recognized as important.

Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

Classification

Cancer is generally classified according to the tissue from which the cancerous cells originate, the primary tumor, as well as the normal cell type they most resemble. These are location and histology, respectively.

Nomenclature

The following closely related terms may be used to designate abnormal growths:

* Tumor: originally, it meant any abnormal swelling, lump or mass. In current English, however, the word tumor has become synonymous with neoplasm, specifically solid neoplasm. Note that some neoplasms, such as leukemia, do not form tumors.
* Neoplasm: the scientific term to describe an abnormal proliferation of genetically altered cells. Neoplasms can be benign or malignant:
o Malignant neoplasm or malignant tumor: synonymous with cancer.
o Benign neoplasm or benign tumor: a tumor (solid neoplasm) that stops growing by itself, does not invade other tissues and does not form metastases.
* Invasive tumor is another synonym of cancer. The name refers to invasion of surrounding tissues.
* Pre-malignancy, pre-cancer or non-invasive tumor: A neoplasm that is not invasive but has the potential to progress to cancer (become invasive) if left untreated. These lesions are, in order of increasing potential for cancer, atypia, dysplasia and carcinoma in situ.

The following terms can be used to describe a cancer:

* Screening: a test done on healthy people to detect tumors before they become apparent. A mammogram is a screening test.
* Diagnosis: the confirmation of the cancerous nature of a lump. This usually requires a biopsy or removal of the tumor by surgery, followed by examination by a pathologist.
* Surgical excision: the removal of a tumor by a surgeon.
o Surgical margins: the evaluation by a pathologist of the edges of the tissue removed by the surgeon to determine if the tumor was removed completely ("negative margins") or if tumor was left behind ("positive margins").
* Grade: a number (usually on a scale of 3) established by a pathologist to describe the degree of resemblance of the tumor to the surrounding benign tissue.
* Stage: a number (usually on a scale of 4) established by the oncologist to describe the degree of invasion of the body by the tumor.
* Recurrence: new tumors that appear a the site of the original tumor after surgery.
* Metastasis: new tumors that appear far from the original tumor.
* Transformation: the concept that a low-grade tumor transforms to a high-grade tumor over time. Example: Richter's transformation.
* Chemotherapy: treatment with drugs.
* Radiation therapy: treatment with radiations.
* Adjuvant therapy: treatment, either chemotherapy or radiation therapy, given after surgery to kill the remaining cancer cells.
* Prognosis: the probability of cure after the therapy. It is usually expressed as a probability of survival five years after diagnosis. Alternatively, it can be expressed as the number of years when 50% of the patients are still alive. Both numbers are derived from statistics accumulated with hundreds of similar patients to give a Kaplan-Meier curve.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:

* Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
* Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
* Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells
* Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
* Blastic tumor: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.

Malignant tumors (cancers) are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer of the liver is called hepatocarcinoma; a cancer of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid). Unfortunately, some cancers also use the -oma suffix, examples being melanoma and seminoma.

from www.wikipedia.org

Hemopoietic Staminal Cell (second part)

2008-07-10T03:27:00.000-07:00

Physical characteristics
With regard to morphology, hematopoietic stem cells resemble lymphocytes. They are non-adherent, and rounded, with a rounded nucleus and low cytoplasm-to-nucleus ratio. Since PHSC cannot be isolated as a pure population, it is not possible to identify them in a microscope. The above description is based on the morphological characteristics of a heterogeneous population, of which PHSC are a component.

Markers
In reference to phenotype, hematopoeitic stem cells are identified by their small size, lack of lineage (lin) markers, low staining (side population) with vital dyes such as rhodamine 123 (rhodamineDULL, also called rholo) or Hoechst 33342, and presence of various antigenic markers on their surface, many of which belong to the cluster of differentiation series, like: CD34, CD38, CD90, CD133, CD105, CD45 and also c-kit- the receptor for stem cell factor. The hematopoietic stem cells are negative for the markers that are used for detection of lineage commitment, and are, thus, called Lin-; and, during their purification by FACS, a bunch of up to 14 different mature blood-lineage marker, e.g., CD13 & CD33 for myeloid, CD71 for erythroid, CD19 for B cells, CD61 for megakaryocytic, etc. for humans; and, B220 (murine CD45) for B cells, Mac-1 (CD11b/CD18) for monocytes, Gr-1 for Granulocytes, Ter119 for erythroid cells, Il7Ra, CD3, CD4, CD5, CD8 for T cells, etc. for mice) antibodies are used as a mixture to deplete the lin+ cells or late multipotent progenitors (MPP)s.
There are many differences between the human and mice hematopoietic cell markers for the commonly-accepted type of hematopoietic stem cells.[1].
* Mouse HSC : CD34lo/-, SCA-1+ , Thy1.1+/lo, CD38+, C-kit+, lin-
* Human HSC : CD34+, CD59+, Thy1/CD90+,CD38lo/-, C-kit/CD117+, lin-
However, not all stem cells are covered by these combinations that nonetheless have become popular. In fact, even in humans, there are hematopoietic stem cells that are CD34-/CD38-. [5][6]. Also some later studies suggested that earliest stem cells may lack c-kit on the cell surface[7]. For human HSCs use of CD133 was one step ahead as both CD34+ and CD34- HSCs were CD133+.
Traditional purification method used to yield a reasonable purity level of mouse hematopoietic stem cells, in general, requires a large(~10-12) battery of markers, most of which were surrogate markers with little functional significance, and thus partial overlap with the stem cell populations and sometimes other closely-related cells that are not stem cells. Also, some of these markers 9eg Thy1) are not conserved across mouse species, and use of markers like CD34- for HSC purification requires mice to be at least 8 weeks old. Alternative methods that could give rise to similar or better harvest of stem cells is a hot area of research and are presently emerging. One such method uses a signature of SLAM family of cell surface molecules. SLAM (Signaling lymphocyte activation molecule) family is a group of >10 molecules whose genes are mostly located tandemly in a single locus on chromosome 1 (mouse), all belonging to a subset of immunoglobulin gene superfamily, and originally thought to be involved in T-cell stimulation. This family includes CD48, CD150, CD244, etc., CD150 being the founding member, and, thus, also called slamF1 ie SLAM family member 1.
The signature SLAM code for the hemapoietic higherchy are:
* Hematopoietic stem cells (HSC) : CD150+CD48-CD244-
* Multipotent progenitor cells (MPPs) : CD150-CD48-CD244+
* Lineage-restricted progenitor cells (LRPs) : CD150-CD48+CD244+
For HSCs, CD150+CD48- was sufficient instead of CD150+CD48-CD244- because CD48 is a ligand for CD244, and both would be positive only in the activated lineage-restricted progenitors. It seems that this code was more efficient than the more tedious earlier set of the large number of markers, and are also conserved across the mouse strains; however, recent work has shown that this method excludes a large number of HSCs and includes an equally large number of non-stem cells. [8] [9]. CD150+CD48- gave stem cell purity comparable to Thy1loSca-1+lin-c-kit+ in mice.[10]
Irving Weissman's group at Stanford University that was the first to isolate mouse hematopoietic stem cells in 1988, was also the first to work out the markers to distinguish the mouse long-term (LT-HSC) and short-term (ST-HSC) hematopoietic stem cells (self-renew-capable), and the Multipotent progenitors (MPP, low or no self-renew capability — the later the developmental stage of MPP, the lesser the self-renewal ability and the more of some of the markers like CD4 and CD135):
* LT-HSC : CD34-, SCA-1+ , Thy1.1+/lo, C-kit+, lin-, CD135-, Slamf1/CD150+
* ST-HSC : CD34+, SCA-1+ , Thy1.1+/lo, C-kit+, lin-, CD135-, Slamf1/CD150+, Mac-1 (CD11b)lo
* Early MPP : CD34+, SCA-1+ , Thy1.1-, C-kit+, lin-, CD135+, Slamf1/CD150-, Mac-1 (CD11b)lo, CD4lo
* Late MPP : CD34+, SCA-1+ , Thy1.1-, C-kit+, lin-, CD135high, Slamf1/CD150-, Mac-1 (CD11b)lo, CD4lo

Nomenclature of hematopoietic colonies and lineages
Between 1948 and 1950, the Committee for Clarification of the Nomenclature of Cells and Diseases of the Blood and Blood-forming Organs issued reports on the nomenclature of blood cells.[11][12] An overview of the terminology is shown below, from earliest to final stage of development:
* [root]blast
* pro[root]cyte
* [root]cyte
* meta[root]cyte
* mature cell name

Osteoclasts also arise from haemopoietic cells of the monocyte/neutrophil lineage, specifically CFU-GM.

Colony-forming units
There are various kinds of colony-forming units:
* Colony-forming unit lymphocyte (CFU-L)
* Colony-forming unit erythrocyte (CFU-E)
* Colony-forming unit granulo-monocyte (CFU-GM)
* Colony-forming unit megakaryocyte (CFU-Me)
* Colony-forming unit Basophil (CFU-B)
* Colony-forming unit Eosinophil (CFU-Eo)
The above CFUs are based on the lineage. Another CFU, the colony-forming unit–spleen (CFU–S) was the basis of an in vivo clonal colony formation, which depends on the ability of infused bone marrow cells to give rise to clones of maturing hematopoietic cells in the spleens of irradiated mice after 8 to 12 days. It was used extensively in early studies, but is now considered to measure more mature progenitor or Transit Amplifying Cells rather than stem cells.

da www.wikipedia.org

Hemopoietic Staminal Cell (first part)

2008-07-04T14:43:00.000-07:00

Hematopoietic stem cells (HSCs) are stem cells that give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells). The definition of hematopoietic stem cells has undergone considerable revision in the last two decades. The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. Recently, long-term transplantation experiments point toward a clonal diversity model of hematopoietic stem cells. Here, the HSC compartment consists of a fixed number of different types of HSC, each with epigenetically preprogrammed behavior. This contradicts older models of HSC behavior, which postulated a single type of HSC that can be continuously molded into different subtypes of HSCs. HSCs constitute 1:10.000 of cells in myeloid tissue.

Source
HSCs are found in the bone marrow of adults, which includes femurs, hip, ribs, sternum, and other bones. Cells can be obtained directly by removal from the hip using a needle and syringe, or from the blood following pre-treatment with cytokines, such as G-CSF (granulocyte colony-stimulating factors), that induce cells to be released from the bone marrow compartment. Other sources for clinical and scientific use include umbilical cord blood, placenta, molilized peripheral blood. For experimental purposes, fetal liver, fetal spleen, and AGM (Aorta-gonad-mesonephros) of animals are also useful sources of HSCs.

Functional Characteristics

Multipotency and self-renewal
As stem cells, they are defined by their ability to form multiple cell types (multipotency) and their ability to self-renew.
It is known that a small number of HSCs can expand to generate a very large number of progeny HSCs. This phenomenon is used in bone marrow transplant when a small number of HSCs reconstitute the hematopoietic system. This indicates that, at least during bone marrow transplant, symmetrical cell divisions that give two progeny HSCs must occur, as expansion in HSC numbers seen during bone marrow transplant cannot occur in any other way.
Stem cell self-renewal is thought to occur in the stem cell niche in the bone marrow, and it is reasonable to assume that key signals present in this niche will be important in self-renewal. There is much interest in the environmental and molecular requirements for HSC self-renewal, as understanding the ability of HSC to replenish themselves will eventually allow the generation of expanded populations of HSC ex vivo that can be used therapeutically.

Lineage-Bias
Using limiting dilution strategies combined with other streamlined experimental and statistical methods for examining HSCs at the clonal level, it was shown that HSCs fall into three distinct lineage-bias[1] [2] [3] clusters. These are quantitatively defined by the ratio ρ of lymphoid to myeloid cells that HSC generate upon differentiation (which makes ρ a peripheral predictor for the clonal association of a reconstituted hematopoietic system). Balanced HSCs repopulate peripheral white blood cells in the same ratio of myeloid to lymphoid cells as seen in unmanipulated mice (on average about 15% myeloid and 85% lymphoid cells, or 3≤ρ≤10). Myeloid-biased (My-bi) HSC give rise to too few lymphocytes resulting in ratios 0 < ρ < 3, whereas lymphoid-biased (Ly-bi) HSC generate too few myeloid cells, which results in lymphoid-to-myeloid ratios of 10 < ρ < oo. All three types are normal HSC in that they have self-renewal capacity and can regenerate all hematopietic lineages (pluripotency). What is striking to note is that the lineage-bias is preserved through multiple rounds of serial transplantation: Balanced HSC self-renew to give rise to daughter HSC that are also balanced, My-bi HSC give rise to My-bi daughter HSC, and Ly-bi produce Ly-bi daughter HSC. There is no precursor-progeny relationship between the three types of HSC and they do not represent stages of differentiation. Rather, these are three classes of HSC, each with an epigenetically-fixed differentiation program.

Functional Assays
Cobble stone area-forming Cell (CAFC) assay: This is a cell culture based empirical assay. When plated onto a confluent culture of stromal feeder layer, a fraction of HSCs creep between the gaps (even though the stromal cells are touching each other) and eventually settle between the stromal cells and the substratum (here the dish surface) or trapped in the cellular processes between the stromal cells. Emperipolesis is the in vivo phenomenon in which one cell is completely engulfed into another (e.g., thymocytes into thymic nurse cells); on the other hand, when in vitro, lymphoid lineage cells creep beneath nurse-like cells, the process is called pseudoemperipolesis. This similar phenomeonon is more commonly known in HSC field by the cell culture terminology cobble stone area-forming cells (CAFC), which means areas of cluster of cells that look dull cobblestone-like under phase contrast microscopy, compared to the other HSCs, which are refractile. This happens because the cells that are floating loosely on top of the stromal cells are spherical and thus refractile. However, the cells that creep beneath the stromal cells are flattened and thus not refractile. The mechanism of pseudoemperipolesis is only recently coming to light. It may be mediated by interaction through CXCR4 (CD184) the receptor for CXC Chemokines (e.g., SDF1) and α4β1 integrins.[4].

Mobility
HSCs have a higher potential than other immature blood cells to pass the bone marrow barrier, and thus may travel in the blood from the bone marrow in one bone to another bone. If they settle in the thymus they'll develop into T cells. In the case of fetuses and other extramedullary hematopoiesis HSCs may also settle in the liver or spleen and develop.
This ability is the reason why HSCs may be harvested directly from the blood.

end first part.... from www.wikipedia.org

Hyperthermia....

2008-06-28T03:25:00.000-07:00

Hyperthermia, in its advanced state referred to as heat stroke or sunstroke, is an acute condition which occurs when the body produces or absorbs more heat than it can dissipate. It is usually due to excessive exposure to heat. The heat-regulating mechanisms of the body eventually become overwhelmed and unable to effectively deal with the heat, therefore the body temperature climbs uncontrollably. This is a medical emergency that requires immediate medical attention.

Hyperthermia can be created artificially by drugs or medical devices. In these instances it may be used to treat cancer and other conditions. Malignant hyperthermia is a rare complication of some types of general anesthesia.

The opposite of hyperthermia is hypothermia, when an organism's temperature drops below that required for normal metabolism.

Difference between hyperthermia and fever
A fever occurs when the body sets the core temperature to a higher temperature, through the action of the pre-optic region of the anterior hypothalamus. For example, in response to a bacterial or viral infection, the body will raise its temperature to allow the immune system to work better and to deteriorate the condition of the invaders. In contrast, hyperthermia occurs when the body temperature is raised without the consent of the heat control centers.

Progression
Body temperatures above 40°C (104 °F) are life-threatening. This compares to normal human body temperature of 36-37°C (97-98°F). At 41°C (106 °F), brain death begins, and at 45°C (113°F) death is nearly certain. Internal temperatures above 50°C (122°F) will cause rigidity in the muscles and certain, immediate death.[citation needed]
Heat stroke may come on suddenly, but usually follows a less-threatening condition commonly referred to as heat exhaustion or heat prostration.
After effects may include sensitivity to heat.

Signs and symptoms
One of the body's most important methods of temperature regulation is perspiration. This process draws heat from inside, allowing it to be carried off by radiation or convection. Evaporation of the sweat furthers cooling, since this endothermic process draws yet more heat from the body. When the body becomes sufficiently dehydrated to prevent the production of sweat this avenue of heat reduction is closed. When the body is no longer capable of sweating core temperature begins to rise swiftly.
Victims may become confused, may become hostile, often experience headache, and may seem intoxicated. Blood pressure may drop significantly from dehydration, leading to possible fainting or dizziness, especially if the victim stands suddenly. Heart rate and respiration rate will increase (tachycardia and tachypnea) as blood pressure drops and the heart attempts to supply enough oxygen to the body. The skin will become red as blood vessels dilate in an attempt to increase heat dissipation. The decrease in blood pressure will cause blood vessels to contract as heat stroke progresses, resulting in a pale or bluish skin colour. Complaints of feeling hot may be followed by chills and trembling, as is the case in fever. Some victims, especially young children, may suffer convulsions. Acute dehydration such as that accompanying heat stroke can produce nausea and vomiting; temporary blindness may also be observed. Eventually, as body organs begin to fail, unconsciousness and coma will result.

First aid
Heat stroke is a medical emergency requiring hospitalization, and the local emergency services should be notified as soon as possible.
The body temperature must be lowered immediately. The victim should be moved to a cool area (indoors, or at least in the shade) and clothing removed to promote heat loss (passive cooling). Active cooling methods may be used: The person is bathed in cool water, a hyperthermia vest can be applied, however, wrapping the victim in wet towels or clothes can actually act as insulation and increase the body temperature. Cold compresses to the torso, head, neck, and groin will help cool the victim. A fan may be used to aid in evaporation of the water (evaporative method). Immersion in ice or cold water is dangerous as this may cause vasoconstriction in the skin, preventing heat from escaping the body core.
Immersing a victim into a bathtub of cool - but not cold - water (immersion method) is a recognized method of cooling. This method requires the effort of 4-5 persons and the victim should be monitored carefully during the treatment process. This should be avoided for an unconscious victim; if there is no alternative, the victim's head must be held above water.
Hydration is of paramount importance in cooling the victim. This is achieved by drinking water (Oral rehydration). Commercial isotonic drinks may be used as a substitute. Some authoritiesare opposed to giving any fluids, except by emergency personnel. Intravenous hydration (via a drip) is necessary if the victim is confused, unconscious, or unable to tolerate oral fluids.
Alcohol rubs will cause further dehydration and impairment of consciousness and should be avoided. The victim's condition should be reassessed and stabilized by trained medical personnel. The victim's heart rate and breathing should be monitored, and CPR may be necessary if the victim goes into cardiac arrest.
The victim should be placed into the recovery position to ensure that the person's airway remains open.

Prevention
The risk of heatstroke can be reduced by observing precautions to avoid overheating and dehydration. Light, loose-fitting clothing will allow perspiration to evaporate. Wide-brimmed hats in bright colour keep the sun from warming the head and neck; vents on a hat will allow perspiration to cool the head. Strenuous exercise should be avoided during daylight hours in hot weather; so should remaining in enclosed spaces (such as automobiles). People who must be outside should be aware that humidity and the presence of direct sunlight may cause the heat index to be 10 °C (18 °F) hotter than the temperature indicated by a thermometer.
In hot weather people need to drink plenty of liquids to replace fluids lost from sweating. Thirst is not a reliable sign that a person needs fluids. A better indicator is the color of urine. A dark yellow color indicates dehydration. Water, not sports drinks, is the most effective in replacing lost fluids. It is recommended that one drinks 6-8 glasses of water each day.[citation needed] Note that it is dangerous to attempt to compensate for heat stroke by drinking a large amount of water quickly, as this can lead to water intoxication, and can be fatal.

Especially susceptible populations
While anyone can be affected by hyperthermia, some populations are especially susceptible to heat illness and injury. As noted by Joseph Rampulla in the The Health Care of Homeless Persons.
Heat illness most seriously affects the poor, urban-dwellers, young children, those with chronic physical and mental illnesses, substance abusers, the elderly, and people who engage in excessive physical activity under harsh conditions.

da www.wikipedia.org

Cancer, Diabetes, and Heart Groups offer Lifestyle Advice

2008-06-26T13:16:00.001-07:00

June 16, 2004 — In an historic combining of forces, The American Cancer Society, American Diabetes Association, and the American Heart Association announced a unified set of health recommendations for the public.

The groups came together to announce a public and professional health education campaign entitled "Everyday Choices for a Healthier Life," which will deliver four simple health messages to the public: First, eat a healthy diet and maintain a healthy weight. Second, be physically active (30 minutes per day 5 days per week). Third, don't smoke and avoid being around others who are smoking; and fourth, see a physician regularly to assess your personal health risks.

The group stated that less than a quarter of Americans eat the recommended 5 servings of fruits or vegetables a day.

To read the full article, go to http://www.reuters.com/newsArticle.jhtml;jsessionid=RJGI44LHBWZNUCRBAELCFEY?type=healthNews&storyID=5429566&pageNumber=0.

Do You Eat the Recommended 5 Servings of Fruits and Vegetables a Day? The June 2002 issue of the Journal of the American Medical Association reports that "most people do not consume an optimal amount of all vitamins by diet alone. . . . It appears prudent for all adults to take vitamin supplements."

Do You Know Your Personal Skin Carotenoid Score? Scientists from around the world are talking about a brand new invention that is on the verge of changing the way people think about antioxidant health - the Pharmanex® BioPhotonic Scanner. This revolutionary tool enables us, for the first time, to measure our level of carotenoid antioxidant protection quickly.

Antioxidants are our frontline defense against the free radicals that constantly affect our cells. Over 30,000 scientific papers have been written about free radicals and antioxidants in the last 20 years. With the Pharmanex® BioPhotonic Scanner we can now obtain an accurate measurement of your personal antioxidant level. By simply placing the palm of your hand in front of a safe, low-energy blue light laser, you obtain an immediate reading of your carotenoid antioxidant level—Skin Carotenoid Score.

To read more about the Pharmanex® BioPhotonic Scanner, visit www.pharmanexscanner.com

http://www.pharmanex.com

FDA Approves Sciele Pharma

2008-06-24T11:16:00.000-07:00

FDA Approves Sciele Pharma, Inc. (SCRX)'s PrandiMet(TM), a Replaglinide and Metformin Fixed-Dose Combination Tablet for Treatment of Type 2 Diabetes
6/24/2008

ATLANTA & PRINCETON, N.J.--(BUSINESS WIRE)--Sciele Pharma, Inc. (NASDAQ:SCRX - News) and Novo Nordisk Inc. today announced that the U.S. Food and Drug Administration (FDA) approved PrandiMet™ (repaglinide and metformin HCl) tablets, the first and only fixed-dose combination of the fast-acting secretagogue replaglinide (also known as Prandin®) and insulin sensitizer, metformin, for the treatment of type 2 diabetes. Under a previously announced agreement, Sciele Pharma will exclusively market PrandiMet™ to physicians in the U.S. Sciele Pharma anticipates that PrandiMet™ will be available to physicians and patients in the U.S. in the second half of 2008.

PrandiMet™ has been approved to lower the blood glucose in adult patients with type 2 diabetes whose hyperglycemia cannot be controlled satisfactorily by meglitinide and/or metformin.

The FDA approved PrandiMet™ based upon data demonstrating that PrandiMet™ 1 mg./500 mg. and 2 mg./500 mg. resulted in similar bioequivalence to co-administration of corresponding doses of repaglinide and metformin HCl as individual tablets.1

“As the world’s leading diabetes care company, Novo Nordisk is dedicated to providing a broad portfolio of treatments that respond to each stage of diabetes. With PrandiMet™, physicians will have a simplified option for Prandin® and metformin combination therapy,” said Jerzy Gruhn, president, Novo Nordisk Inc.

PrandiMet™ is the first and only fixed-dose combination of a fast-acting secretagogue and metformin. The combination of metformin and repaglinide has been shown to safely and effectively reduce hemoglobin A1c levels. PrandiMet™ offers the convenience of two medications in one pill. PrandiMet™ is comprised of two well-established anti-diabetic medications: Prandin®, a fast-acting insulin secretagogue and metformin, an insulin sensitizer. Prandin® stimulates the release of insulin from the pancreas after a meal, thereby reducing PPG. Metformin decreases the amount sugar produced by the liver, reducing FPG, and helps the body respond better to the insulin it makes naturally.

“We are very pleased with approval of PrandiMet™, an important new treatment option for people struggling to keep their blood glucose in control,” said Patrick Fourteau, Chief Executive Officer of Sciele Pharma, Inc. “We’ve seen that many patients need more than one therapy to control their type 2 diabetes and the combination of Prandin® and metformin in one pill will give patients convenient access to two medications trusted for their efficacy and safety.”

About PrandiMet™

PrandiMet™ is indicated for the treatment of type 2 diabetes and includes two products with well-established data for safety and efficacy: repaglinide (Prandin®) and metformin. It is the first fixed-dose combination of a fast acting insulin secretagogue and metformin, combining two antihyperglycemic agents with different mechanisms of action in one tablet to improve glycemic control.

PrandiMet™ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a meglitinide and metformin HCl or who have inadequate glycemic control on a meglitinide alone or metformin HCl alone. Do not use to treat type 1 diabetes or diabetic ketoacidosis.

Lactic acidosis can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure. Symptoms include malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. If acidosis is suspected, discontinue PrandiMet™ and hospitalize the patient immediately.

PrandiMet™ is contraindicated in patients with renal impairment, metabolic acidosis, including diabetic ketoacidosis, or patients receiving both gemfibrozil and itraconazole. Before initiation of therapy with PrandiMet™ and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal impairment is anticipated, renal function should be assessed more frequently and PrandiMet™ discontinued if evidence of renal impairment is present. PrandiMet™ should generally be avoided in patients with hepatic impairment.

PrandiMet™ should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials and may be resumed 48 hours after the procedure only after renal function has been re-evaluated and found to be normal. Repaglinide is not indicated for use in combination with NPH insulin.

Hypoglycemia and headache were the most common adverse reactions (=10%) reported among patients treated with repaglinide in combination with metformin HCl. Gastrointestinal reactions (e.g. diarrhea, nausea, and vomiting) are the most common adverse reactions with metformin HCl treatment and are more frequent at higher metformin HCl doses.

PrandiMet™ works to control three abnormalities of type 2 diabetes: impaired insulin secretion; insulin resistance and excessive hepatic glucose production.

PrandiMet™ is available in two dosage strengths – 1mg. (repaglinide)/500mg. (metformin) and 2 mg. (repaglinide)/500mg. (metformin), recommended to be dosed at two-three times a day with meals.

Full prescribing information for PrandiMet™ is available by contacting Novo Nordisk Inc. or visiting www.prandimet.com.

About Type 2 Diabetes

Type 2 Diabetes (diabetes mellitus) is a serious chronic disease in which the body does not produce or properly use insulin. Insulin is a hormone needed to convert sugar, starches and other food into energy needed for daily life.

In the United States, an estimated 20.8 million people have diabetes (7% of the population). Of the total, 6.2 million remain undiagnosed and about 1.5 million new cases of diabetes are diagnosed each year.2 Only 57% of those with diabetes are meeting the recommended glucose levels (hemoglobin A1c goal of 7.0% or less)3 and those who are undiagnosed or not controlled are putting themselves at risk for serious complications.

About Novo Nordisk

Novo Nordisk is a healthcare company with an 85-year history of innovation and achievement in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition to diabetes care, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk’s business is driven by the Triple Bottom Line: a commitment to social responsibility to employees and customers, environmental soundness and economic success. With headquarters in Denmark, Novo Nordisk employs more than 26,000 employees in 80 countries, and markets its products in 179 countries. Novo Nordisk’s B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO.' For global information, visit novonordisk.com; for United States information, visit novonordisk-us.com.

About Sciele Pharma, Inc.

Sciele Pharma, Inc. is a pharmaceutical company specializing in sales, marketing and development of branded prescription products focused on Cardiovascular, Diabetes, Women’s Health and Pediatrics. The Company’s Cardiovascular and Diabetes products treat patients with high cholesterol, hypertension, high triglycerides, unstable angina and Type 2 diabetes; its Women’s Health products are designed to improve the health and well-being of women and mothers and their babies; and its Pediatrics products treat allergies, asthma, coughs and colds, and attention deficit and hyperactivity disorder (ADHD). Founded in 1992 and headquartered in Atlanta, Georgia, Sciele Pharma employs more than 900 people. The Company’s success is based on placing the needs of patients first, improving health and quality of life, and implementing its business platform - an Entrepreneurial Spirit, Innovation, Execution Excellence, Simplicity, and Teamwork.

Safe Harbor Statement

This press release contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to materially differ from those described. Although we believe that the expectations expressed in these statements are reasonable, we cannot promise that our expectations will turn out to be correct. Our actual results could be materially different from and worse than our expectations. With respect to such forward-looking statements, we seek the protections afforded by the Private Securities Litigation Reform Act of 1995. These risks include, without limitation:

We may not attain expected revenues and earnings. If we are unsuccessful in obtaining or renewing third party payor contracts for our products, we may experience reductions in sales levels and may fail to reach anticipated sales levels. If demand for our products exceeds our initial expectations or the ability of our suppliers to provide demand-meeting quantities of product and samples, our future ability to sell these products could be adversely impacted. The potential growth rate for our promoted products may be limited by slower growth for the class of drugs to which our promoted products belong and unfavorable clinical studies about such class of drugs. We will not realize anticipated sales if our products and our licensors’ products do not receive regulatory approval.

We may encounter problems in the manufacture or supply of our products, for which we depend entirely on third parties. Strong competition exists in the sale of our promoted products, which could adversely affect expected growth of our promoted products’ sales or increase our costs to sell our promoted products. We may not be able to protect our competitive position for our promoted products from patent infringers. If generic competitors that compete with any of our products are introduced, our revenues may be adversely affected.

Certain of our products have experienced manufacturing issues. If the issues recur and cannot be resolved, our ability to acquire product for sale and sampling will be adversely affected. We may incur unexpected costs in integrating new products into our operations.

We may be unable to develop or market line extensions for our products or, even if developed, obtain patent protection for our line extensions; further, introductions by us of line extensions of our existing products may require that we make unexpected changes in our estimates for future product returns and reserves for obsolete inventory. If these risks occur, our financial results could be adversely affected.

If we have difficulties acquiring new products or rights to market new products from third parties, our financial results could be adversely impacted. Our licensor/supplier can terminate our rights to commercialize Nitrolingual and the 60mg dose size of this product has not yet met our expectation.

We may not experience the beneficial results of our acquisitions that we expect to receive, and the acquired products may not meet our sales expectations.

We depend on a small senior management group, the departure of any member of which would likely adversely affect our business if a suitable replacement member could not be retained.

An adverse interpretation or ruling by one of the taxing jurisdictions in which we operate could adversely impact our operating results. An adverse judgment in the pending patent litigation involving Prandin or in the securities class action litigation in which we and certain current and former directors and executive officers are defendants could have a material adverse effect on our financial results and liquidity.

Our business is subject to increasing government price controls and other healthcare cost containment measures. Side effects or marketing or manufacturing problems with our products could result in product liability claims which could be costly to defend and could result in the withdrawal or recall of products from the market which would adversely affect our business. We may be found noncompliant with applicable federal, state or international laws, rules or regulations which could result in fines and/or product recalls or otherwise cause us to expend significant resources to correct such non-compliance.

A small number of customers account for a large portion of our sales and the loss of one of them, or changes in their purchasing patterns, could result in substantially reduced sales, substantially and adversely impacting our financial results. If third-party payors do not adequately reimburse patients for our products, doctors may not prescribe them.

We rely on operational data obtained from IMS, an industry accepted data source. IMS data may not accurately reflect actual prescriptions (for instance, we believe IMS data does not capture all product prescriptions from some non-retail channels).

Our business and products are highly regulated; the regulatory status of some of our products makes these products subject to increased competition and other risks; and we run the risk that we, or third parties on whom we rely, could violate the governing regulations.

Some unforeseen difficulties may occur.

The above are some of the principal factors that could cause actual results to differ materially from those described in the forward-looking statements included above. These factors are not intended to represent a complete list of all risks and uncertainties inherent in our business, and should be read in conjunction with the more detailed cautionary statements and risk factors included in our other filings with the Securities and Exchange Commission.

(1) Moses, et al. “Effect of replaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.” Diabetes Care, 22 (1999): 119 - 122

(2) Centers for Disease Control. “CDC’s Diabetes Program: National Diabetes Fact Sheet.” http://www.cdc.gov/diabetes/pubs/estimates05.htm#prev. Also, American Diabetes Association. “All About Diabetes: Overview,” http://www.diabetes.org/about-diabetes.jsp.

(3) Hoerger, et al. “Is glycemic control improving in US adults?” Diabetes Care 13 (2008):81-86.

Contact:

Sciele Pharma, Inc. Joseph T. Schepers Director of Investor Relations 678-341-1401 ir@sciele.com or Novo Nordisk Media Inquiries: Sean Clements, 609-902-9164 or Investor Inquiries: Christian Qvist Frandsen, 609-919-7937

Source: Sciele Pharma, Inc.
da www.biospace.com

Should Doctors Be 'Selling' Drugs for the Pharmaceutical Industry?

2008-06-22T02:58:00.000-07:00

Feature: Key opinion leaders -- independent experts or drug representatives in disguise?

LONDON, June 19, 2008-Are senior doctors who help drug companies sell their drugs independent experts or just drug representatives in disguise, asks Ray Moynihan from the University of Newcastle in Australia, in this week's BMJ.

Moynihan exposes the reality behind the practice with some candid revelations from industry insiders.

Pharmaceutical companies regularly sponsor leading specialists with "generous fees to peddle influence" and promote drugs to the profession and the public, writes Moynihan.

Drug companies will pay influential doctors up to $400 an hour to act as key opinion leaders, and some doctors earn more than $25 000 a year in advisory fees.

Kimberly Elliot, a former award-winning drug company sales representative interviewed* by Moynihan, reveals that drug companies desperately need key opinion leaders in order for doctors to believe what they are saying and prescribe their products, because drug representatives are often not believed. Essentially, she says, key opinion leaders are just salespeople.

So how independent are these doctors who have long term financial arrangements with drug companies?

According to Richard Tiner, medical director at the Association of the British Pharmaceutical Industry, although "the work might help to promote a particular medicine" it should be considered payment for work done, and not a bribe. The best antidote to concerns about independence would be more transparency—all company payments to speakers should be routinely disclosed at medical meetings, he adds.

But David Blumenthal, from Harvard University, believes that payments to key opinion leaders are not in the public interest or in the interests of the patients served by these doctors, and calls for a major cutback in industry influence over the medical profession and its education.

In an accompanying head to head, Charlie Buckwell, Chief Executive of the Complete Medical Group and Professor Giovannii Fava, from the University of Bologna, debate whether drug companies' use of medical experts is essential for medical advancement or whether it risks scientific integrity.

###

Contact: Rachael Davies

da www.drugs.com

cellule staminali.... le cure per il futuro...

2008-06-20T06:48:00.001-07:00

Proroga decreto conservazione autologa

IL MINISTERO ANNUNCIA PROROGA- Sono stati prorogati dal ministero del Lavoro, della Salute e delle Politiche sociali sino al 28 febbraio 2009 i termini di validita' dell'ordinanza sulla raccolta di cellule staminali dal cordone ombelicale del ministro Turco. La nuova normativa prevedeva, infatti, che alla data del 30 giugno fosse pronto il decreto attuativo contenente le regole e i criteri per la costituzione di una rete di banche dedicate alla conservazione di queste cellule. Le elezioni anticipate e l'insediamento del nuovo governo hanno inevitabilmente creato ritardi in alcune fasi essenziali per il completamento delle procedure da seguire per la creazione di questa rete. Da qui la necessita' di una proroga dei termini previsti sino al 2009.

La conservazione autologa presso centri specializzati all'estero è l'alternativa rispetto alla esclusiva donazione eterologa oggi in vigore che, tra l'altro, e' pressoche' impossibile perche' neppure il 10% dei punti nascita e' attrezzato e, quando lo e', ci sono forti limitazioni nei festivi e di notte. ''Non c'e' da stupirsi - dice l'on. Poretti - percio' che nel 2007 siano state piu' di cinquemila le autorizzazioni del ministero per la conservazione del proprio cordone in banche estere (cosi' come prevede l'attuale normativa), circa il doppio dei cordoni donati'.''

sa www.salusfutura.com

la cura contro il cancro

2008-06-19T11:31:00.000-07:00

«Normogen» - a brand new method of treatment
of oncologic diseases

Kazakhstan biologists and immunologists have been studying the causes of malignant cells nascency during 25 years. The result of their study is a brand new method of treatment of oncologic diseases.

The method is based on the natural mechanism of control over cells division and differentiation by means of special protein compounds, immunoglobulins. We have succeeded in defining these compounds, which turned out to be anti-idiotypic antibodies to alfa-fetorpotein.

We have determined by experiment that these antibodies as well as alfa-fetorpotein itself can bind selectively with changed cells.

Complement protein, which is present in the body, causes destruction of the changed cells, "labeled" with these antibodies. At that no damage is caused to normal cells of the body.

With the use of the combination of these defined protein components we have managed to create the drug, which can destruct malignant cells of the body selectively.

da www.normogen.com

Colesterolo? A voi il Lipozid.... ma leggete bene...

2008-06-18T12:34:00.000-07:00

LIPOZID
COMPOSIZIONE QUALITATIVA E QUANTITATIVA
600 mg compresse rivestite con film principio attivo gemfibrozil mg 600 900 mg compresse rivestite con film principio attivo gemfibrozil mg 900

FORMA FARMACEUTICA
Compresse rivestite con film.

INFORMAZIONI CLINICHE
Indicazioni terapeutiche
Dislipidemie caratterizzate da aumento dei trigliceridi che non rispondono al trattamento dietetico.
E' anche efficace nelle iperlipoproteinemie che non rispondono al trattamento dietetico.

Posologia e modo di somministrazione
La dose consigliata è di 1200 mg giornalieri: 2 compresse da 600 mg, da assumere prima dei pasti principali. La dose può essere ridotta ad 1 compressa da 900 mg da assumere alla sera, una volta ottenuto un soddisfacente risultato sul quadro lipidemico. Durante la terapia con LIPOZID vanno rispettate le necessarie misure dietetiche.

Controindicazioni
Insufficienza renale e/o epatica, compresa la cirrosi biliare primitiva. Preesistenti affezioni calcolotiche della cistifellea. Ipersensibilità accertata al farmaco.

Speciali avvertenze e precauzioni per l'uso
Poiché la risposta individuale all'azione biochimica del gemfibrozil è variabile, non sempre è possibile anticipare, in base al quadro lipoproteico, se il paziente otterrà un risultato positivo dal trattamento. Si consiglia quindi di effettuare frequenti determinazioni del tasso ematico delle varie frazioni lipidiche. In caso di risposta terapeutica inadeguata dopo 3 mesi, si consiglia di sospendere il trattamento. Lievi decrementi dell'emoglobina, dell'ematocrito nonché del numero dei globuli bianchi sono stati occasionalmente riscontrati in alcuni pazienti all'inizio della terapia. Tali valori tuttavia si sono normalizzati nel prosieguo del trattamento. Si raccomanda di eseguire periodicamente l'esame emocromocitometrico durante i primi 12 mesi di terapia.
Alterazioni della funzionalità epatica sono state riscontrate occasionalmente durante il trattamento con LIPOZID. I livelli di SGOT, SGPT, LDH e fosfatasi alcalina si normalizzano generalmente con l'interruzione della terapia. Si raccomanda di eseguire periodicamente gli esami della funzionalità epatica. La persistenza di alterazioni nel prosieguo della terapia ne impone l'interruzione. Il gemfibrozil può aumentare la secrezione biliare di colesterolo, con eventuale sviluppo di colelitiasi.
In tal caso il trattamento con LIPOZID va interrotto. La somministrazione a ratti maschi di dosi di gemfibrozil da 3 a 10 volte superiori a quella umana per 10 settimane, ha indotto una riduzione della fertilità di tipo dose-dipendente. Successivi studi hanno dimostrato che questo effetto è reversibile entro 8 settimane dalla sospensione del trattamento e non è trasmesso alla prole. Sebbene non siano state segnalate alterazioni significative del ritmo cardiaco attribuibili al trattamento con gemfibrozil, disturbi di questo tipo si sono instaurati dopo trattamento con farmaci simili. Da usare con cautela nei pazienti con un'anamnesi di epatopatia o ulcera peptica.
Misure dietetiche adeguate rappresentano comunque il primo approccio terapeutico per il trattamento delle iperlipoproteinemie sopra indicate. L'eccesso di peso corporeo e l'eccessivo consumo di bevande alcoliche, fattori importanti nella genesi delle ipertrigliceridemie, dovrebbero essere corretti prima di ogni terapia farmacologica.
La concomitante presenza di malattie come l'ipotiroidismo ed il diabete mellito impongono l'istituzione di terapia adeguata, tale terapia combinata andrà condotta con molta cautela.
La sicurezza e l'efficacia del farmaco nei bambini non è stata stabilita.

Interazioni
Particolare cautela dovrebbe essere usata quando LIPOZID è somministrato con anticoagulanti. Il dosaggio di questi ultimi deve essere convenientemente ridotto in modo da mantenere il tempo di protrombina al livello utile per prevenire complicanze emorragiche. E' consigliabile controllare frequentemente il tempo di protrombina sino alla sua normalizzazione. Non utilizzare in associazione con gli inibitori della HMGCoA reduttasi (statine). In pazienti nei quali gli inibitori dell'HMG-CoA reduttasi venivano somministrati contemporaneamente al LIPOZID, sono state riportate gravi miopatie e rabdomiolisi.

Gravidanza e allattamento
L'innocuità del farmaco somministrato durante la gravidanza e l'allattamento non è stata accertata.

Effetti sulla capacità di guidare veicoli e sull'uso di macchine
Non sono stati segnalati effetti negativi.

Effetti indesiderati
Gli effetti collaterali più frequentemente riscontrati sono rappresentati in ordine di frequenza decrescente da:
dolore addominale, dolore epigastrico, diarrea, nausea, vomito e flatulenza.
Talora sono stati descritti: rash, dermatite, prurito, orticaria, cefalea, vertigine, offuscamento del visus, dolore alle estremità, anemia, eosinofilia, leucopenia. Le lievi e sporadiche riduzioni dell'ematocrito e dei leucociti si normalizzano di regola senza interruzione del trattamento. Gli sporadici aumenti di SGOT e SGPT, della LDH e della fosfatasi alcalina che si sono osservati durante la terapia con gemfibrozil, rientrano nella norma quando il trattamento è stato interrotto. Altre reazioni secondarie riportate, di cui però non è sicura la relazione causale con la somministrazione di LIPOZID sono:
secchezza delle fauci, anoressia, stipsi, meteorismo, dispepsia, dolori alla schiena, artralgie, crampi muscolari, mialgia, insonnia, parestesie, tinnitus, astenia, malessere.

Sovradosaggio
Casi di sovradosaggio non sono stati descritti. Tuttavia, nel caso ciò dovesse verificarsi, dovranno essere adottate idonee terapie sintomatiche.

PROPRIETA' FARMACOLOGICHE
Proprietà farmacodinamiche
Il gemfibrozil riduce il livello dei trigliceridi plasmatici nei ratti e nelle scimmie normali ed inibisce l'ipertrigliceridemia indotta da fruttosio nel ratto; in vivo inibisce la lipolisi del tessuto adiposo nel ratto.
Nello stesso animale sottoposto a dieta normale o ricca di colesterolo, il gemfibrozil induce un notevole aumento del colesterolo delle lipoproteine ad alta densità (HDL).
Analogamente nell'uomo induce significative riduzioni dei livelli di trigliceridi plasmatici ed esercita un'azione di normalizzatore lipidemico, riducendo il colesterolo delle lipoproteine a bassa densità (LDL e VLDL) ed aumentando quello delle lipoproteine ad alta densità (HDL), con conseguente probabile effetto antiaterogeno.

Proprietà farmacocinetiche
Nell'animale e nell'uomo il gemfibrozil è assorbito rapidamente e completamente. Gli studi di farmacocinetica hanno dimostrato che il gemfibrozil nel ratto e nel cane è principalmente escreto per via fecale con intensa circolazione enteroepatica soprattutto nel cane, al contrario, nella scimmia e nell'uomo, il prodotto viene soprattutto eliminato per via urinaria (più del 60%). Sia nell'animale che nell'uomo il prodotto è escreto in forma coniugata, sia inalterato che metabolizzato. I principali metaboliti identificati sono un composto ossidrilato sul nucleo aromatico e composti nei quali un metile xilolico è ossidrilato o ossidato a gruppo carbossilico.

Dati preclinici di sicurezza
Nelle prove di tossicità acuta sull'animale il gemfibrozil ha dimostrato una buona tollerabilità (DL50 3160 mg/Kg nel topo e 4790 mg/Kg nel ratto). Nelle prove di tossicità cronica nel ratto e nel cane la somministrazione per os di dosi fino a 300 mg/Kg per 12 mesi non ha dato effetti secondari.

INFORMAZIONI FARMACEUTICHE
Eccipienti
600 mg compresse rivestite con film: cellulosa microcristallina; amido pregelatinizzato; silice precipitata; polisorbato 80; magnesio stearato; sodio carbossimetilamido;filmatura:
idrossipropilmetilcellulosa; titanio biossido; talco; polietilenglicole; simeticone. 900 mg compresse rivestite con film:
silice precipitata; amido pregelatinizzato; polisorbato 80; magnesio stearato; sodio carbossimetilamido; filmatura:
idrossipropilmetilcellulosa; titanio biossido; talco; polietilenglicole 6000; simeticone.

Incompatibilità
Non sono noti casi di incompatibilità chimico-fisiche con altre sostanze.

Periodo di validità
4 anni

Speciali precauzioni per la conservazione
Nessuna

Natura e contenuto della confezione
LIPOZID 600 mg compresse rivestite con film - 30 compresse in blister LIPOZID 900 mg compresse rivestite con film – 20 compresse in blister

Istruzioni per l'uso e la manipolazione
Nessuna

TITOLARE DELL'AUTORIZZAZIONE ALL'IMMISSIONE IN COMMERCIO
PHARMACIA ITALIA S.p.A. – Milano

NUMERO DI AUTORIZZAZIONE ALL'IMMISSIONE IN COMMERCIO
LIPOZID 600 mg compresse rivestite con film AIC n. 025443060 LIPOZID 900 mg compresse rivestite con film AIC n. 025443096

REGIME DI DISPENSAZIONE AL PUBBLICO

DATA DELLA PRIMA AUTORIZZAZIONE/RINNOVO DELL'AUTORIZZAZIONE
LIPOZID 600 mg compresse rivestite con film aprile 1985/giugno 2000 LIPOZID 900 mg compresse rivestite con film febbraio 1991/giugno 2000

TABELLA DI APPARTENENZA DPR 309/90

DATA DI REVISIONE DEL TESTO
Marzo 2003

da http://www.torrinomedica.it

una malattia del passato..... o forse no.... il Lupus

2008-06-17T07:04:00.000-07:00

Il Lupus eritematoso sistemico (LES) è una malattia cronica rara di natura autoimmune, che può colpire diversi organi e tessuti del corpo. Autoimmune significa che c’è una disfunzione del sistema immunitario che, invece di proteggere il corpo da virus, batteri e agenti estranei, produce auto-anticorpi che aggrediscono i propri componenti.
Generalmente con il semplice termine di Lupus ci si riferisce al Lupus eritematoso sistemico, nonostante esistano altre patologie che comprendono lo stesso nome (per esempio Lupus anticoagulante o sindrome da antifosfolipidi).
Il LES è classificato come malattia reumatica.

Epidemiologia e cenni storici
Il nome Lupus eritematoso sistemico risale all'inizio del XX secolo. Lupus è la parola latina che significa lupo, e si riferisce alla caratteristica eruzione cutanea a forma di farfalla riscontrata sul viso di molti pazienti affetti da LES, che ricordava ai medici i contrassegni bianchi presenti sul muso dei lupi. Eritematoso si riferisce al rossore della pelle. Sistemico significa che interessa diversi organi del corpo.
L'esordio della malattia è inusuale prima del quinto anno d'età ed insolito prima dell'adolescenza dove si ritrovano casi più frequenti nei maschi. In questa fascia d'età il LES colpisce 5 bambini per milione l'anno.
L'esordio avviene più comunemente in età fertile (da 15 a 45 anni) e più frequentemente nella popolazione femminile (in questo gruppo d'età 9 casi su 10 sono donne). Uno studio compiuto negli Stati Uniti d'America ha mostrato una maggiore incidenza del LES nelle donne d'origine afro-americana, ispanica, asiatica e indigena, ma si ritiene che ciò sia dovuto a fattori socioeconomici.
In Italia si stima che oggi i casi seguiti clinicamente riguardino circa 60000 persone, con un incremento di circa 1500 nuovi casi diagnosticati ogni anno; a seguito di questa stima, in Italia il LES, che fino a tutto il 2005 era considerato una malattia rara, dal 2006 è stato riclassificato come malattia cronica e invalidante (dà diritto all'invalidità civile). Altre stime invece portano a contare solo 11000 pazienti nel nostro paese, vale a dire un malato ogni 5000 abitanti.

Eziologia
La malattia non è ereditaria e non è assolutamente trasmissibile da uomo a uomo. Tutt'oggi non si conoscono le cause specifiche del LES, anche se ci sono alcuni punti fermi: predisposizione genetica in primis (non sono rari i casi di più soggetti affetti da LES nello stesso nucleo familiare), fattori ambientali (molto probabilmente: esposizione al sole, infezioni da virus o batteri, stress, alcuni medicinali, ...), età in cui sono in atto modifiche ormonali (pubertà, gravidanza, menopausa, ...).

Clinica: Segni e sintomi
La diagnosi del LES è molto difficile: nei paesi anglosassoni è conosciuto come the great imitator, cioè il grande imitatore. La malattia può manifestarsi con dolori alle articolazioni, affaticamento anomalo, febbre, manifestazioni cutanee, perdita di capelli, ulcere alle mani, anemia, tendiniti, pleuriti, nefriti, pericarditi, ma il fattore più indicativo è la sistemicità di questi sintomi, cioè colpiscono diversi organi contemporaneamente.
C'è da dire, comunque, che i sintomi, nonché l'andamento della malattia, possono cambiare anche di molto da soggetto a soggetto. La malattia può manifestarsi con svariate sfumature diverse, e infatti è conosciuta anche come la malattia dai mille volti.

Trattamento
Non esiste ancora una cura definitiva, ma è possibile trattare la malattia, soprattutto per cercare di portarla in uno stato di remissione, cioè farla regredire ad uno stato simile alla guarigione; a oggi non si guarisce dal LES, la malattia resta sempre presente anche nei periodi di remissione, e va tenuta costantemente sotto controllo.
In questi ultimi anni sono stati compiuti progressi nel trattamento di questa malattia.[citazione necessaria]

Farmacologico
L'intervento terapeutico è diverso a seconda del quadro clinico: nei casi lievi si procede al trattamento con alcuni farmaci antimalarici (idrossiclorochina) associati a cortisone o altri antiinfiammatori; nei casi più severi occorre utilizzare anche farmaci immunosoppressori, i quali impediscono la moltiplicazione dei linfociti B responsabili della produzione di auto-anticorpi.
Data la molteplicità (e la gravità) dei sintomi della malattia e degli effetti collaterali dei medicinali, si è costretti molte volte ad assumere anche altri farmaci.

tratto da www.wikipedia.it

iniziamo con qualcosa che molti conoscono.... il prozac.... ;-)

2008-06-16T12:21:00.000-07:00

DA WWW.SOCIALNEWS.IT

Prozac ai minori
Oltre il limite!

Il farmaco è muto, non racconta la favole ai bambini. Però addormenta, calma, euforizza, riduce i sintomi senza curare le cause del disagio infantile. La decisione dell’AIFA di autorizzare la prescrizione della Fluoxetina anche ai più piccoli fa seguito alla analoga decisone dell’EMEA, l’Agenzia europea dei farmaci, e autorizza il superamento del limite simbolico, della prescrizione delle pillole della felicità ai bambini di 8 anni e oltre

Il 28 marzo 2007 l’AIFA (Agenzia Italiana del Farmaco) ha autorizzato la prescrizione della Fluoxetina ai bambini di 8 anni e oltre per la cura della depressione. Il decreto pubblicato sulla Gazzetta Ufficiale del 26 marzo recita:

•“Aggiunta indicazione terapeutica: Bambini e adolescenti di 8 anni di età ed oltre su diagnosi e piano terapeutico degli specialisti in neuropsichiatria infantile o psichiatria: episodio di depressione maggiore di grado da moderato a grave, se la depressione non risponde alla psicoterapia dopo 4-6 sedute. La terapia con antidepressivo deve essere proposta ad un bambino o ad una persona giovane con depressione da moderata a grave solo in associazione con una contemporanea psicoterapia…”. La decisione dell’AIFA che fa seguito alla analoga decisone dell’EMEA, l’agenzia europea dei farmaci, segnala così, con la sua autorizzazione ufficiale, il superamento di un limite simbolico, e cioè la prescrizione delle pillole della felicità ai bambini di 8 anni e oltre. Che l’evento sia un vero e proprio segno dei tempi e che riveli ormai la supremazia del Discorso del padrone (così come è stato illuminato da Jacques Lacan) veicolato dalle multinazionali del farmaco è un fatto che sta, purtroppo, sotto gli occhi di tutti. Inoltre questa decisione, mina alle radici un’ Etica delle cure dei bambini che non deve rinunciare ai suoi assunti di fondo, e cioè:

1. Le cause del malessere e della sofferenza psicologica dei bambini sono riconducibili, nelle stragrande maggioranza dei casi, al malfunzionamento dei legami affettivi di base con le figure di accudimento, alla cattive parole degli adulti che li crescono ed alla devastazione di una società, immersa in una rincorsa immaginaria all’apparenza ed al consumo di oggetti inutili.

2. Quando si ascolta un bambino che sta male o se si osserva il suo agire sofferente è quasi sempre reperibile nella coppia genitoriale e nella famiglia allargata una sofferenza altrettanto elevata, tanto da far pensare molto spesso che il bambino sia il sintomo del malessere di mamma e papà.

3. Famiglie patologiche, famiglie disfunzionali, famiglie conflittuali, famiglie frammentate o incapaci di proteggere adeguatamente i figli fanno quasi sempre da cornice alle depressioni infantili.

4. Malesseri relazionali, violenze tra pari, marginalizzazioni e rifiuti amplificano ed incrementano la depressione dei giovani adolescenti.

Ora il farmaco nella sua illusoria onnipotenza dovrebbe sopperire, secondo i nuovi protocolli dell’AIFA, alle male parole, ai cattivi accudimenti ed alle carenze affettive e supportive delle frammentate e fragili famiglie ipermoderne? È evidente che ci troviamo di fronte ad un vero e proprio corto circuito epistemologico che volutamente vuole misconoscere la complessa eziopatogenesi dei disturbi dell’umore nei bambini, che, di contro, necessiterebbero, per coerenza logica, di un altrettanto complesso e globale intervento sulle cause disfunzionali delle famiglie piuttosto che arrestarsi su un modello di cura che fa del farmaco-droga il lenimento del senso di colpa degli adulti e dà loro una facile fuga dalla responsabilità. Apparentemente, il protocollo dell’AIFA é corretto quando rinvia l’assunzione del farmaco a dopo l’eventuale non efficacia di 4 o 6 sedute di psicoterapia. Ora chi opera quotidianamente nel campo psicoterapeutico sa che 4 o 6 sedute di psicoterapia nel trattamento di casi gravi sono un tempo irrisorio, quando è del tutto evidente che un trattamento veramente trasformativo dei sintomi e stabilizzatore della personalità comporta tempi molto più lunghi, alle volte di molti anni di lavoro assiduo con il bambino e con la sua famiglia.

Inoltre, è noto che sono molto pochi i bambini e gli adolescenti che possono usufruire anche di una psicoterapia breve, per cui il vincolo delle 4 o 6 sedute sarà ben presto dimenticato a favore di una prescrizione di pillole di massa, per far finta di curare, in assenza di buone parole, il malessere esistenziale e psicologico dei nostri bambini e dei nostri adolescenti.

Il farmaco è muto, non racconta la favole ai bambini, addormenta, calma, euforizza, riduce i sintomi ma non cura le cause del disagio infantile. Affermare il contrario significa spingere i bambini a conformarsi al modello farmaco-droga-benessere. Del resto sempre più i nostri adolescenti ricorrono ad alcol e pasticche di ogni tipo. Se queste sono le cure! Il bugiardino del Prozac® che accompagna il prodotto evidenzia nelle raccomandazioni il seguente avvertimento:

• Assunzione da parte di bambini e adolescenti di età inferiore ai 18 anni. Comportamenti correlati al suicidio (tentativo di suicidio e ideazione suicidaria) e ostilità (essenzialmente aggressività, comportamento di opposizione e collera) sono stati osservati con maggiore frequenza negli studi clinici effettuati su bambini e adolescenti trattati con antidepressivi rispetto a quelli trattati con placebo. PROZAC® deve essere utilizzato nei bambini e adolescenti di età compresa tra gli 8 e i 18 anni solo per il trattamento degli episodi di depressione maggiore di grado da moderato a grave e non deve essere usato in altre indicazioni. Qualora, in base ad esigenze mediche, dovesse essere presa la decisione di effettuare il trattamento, il paziente deve essere sorvegliato attentamente per quanto concerne la comparsa di sintomi suicidari. Per di più, nei bambini e negli adolescenti sono disponibili solo dati limitati per quanto concerne gli effetti a lungo termine sulla sicurezza, inclusi gli effetti sulla crescita, sulla maturazione sessuale e sullo sviluppo cognitivo, emotivo e comportamentale . Ci si chiede come Farmacologi di fama internazionale possano tranquillamente far prescrivere dei farmaci ai bambini con il rischio che questi potenzino suicidi e gravi disturbi della personalità, proprio nel momento in cui solo loro stessi a denunciare un pericolo reale. Tutto ciò appare inconcepibile! Ancora più grave e per di più! I farmacologi non sanno neppure dirci quali saranno le conseguenze del farmaco sulla crescita, sullo sviluppo sessuale e sullo sviluppo psicologico globale dei bambini in trattamento. Come è possibile che medici di medicina generale, pediatri e neuropsichiatri infantili siano autorizzati a prescrizioni (che nel tempo assumeranno una incidenza esponenziale) quando le conseguenze a lungo termine del farmaco non sono note? È questa una corretta Etica delle cure? Forse la proposta dell’On. Cancrini presentata al Parlamento il 4 maggio 2006 intitolata “Norme per l’accesso alla psicoterapia” potrebbe facilitare per molti bambini ed adolescenti in situazione di disagio una vera occasione di cura, al di là dei rivoli di farmaco muto promosso dalle multinazionali per addormentare gli uomini e le donne di domani.

Gelindo Castellarin
Psicologo, psicoterapeuta, psicoanalista SLP

DA WWW.SOCIALNEWS.IT

pharmacy... medicines....care....

2008-06-16T11:51:00.000-07:00

in questo blog parleremo delle medicine, dei farmaci e delle cure che utilizzano questi farmaci....
spero sia di aiuto... ;-)