Nonsteroidal Anti-inflammatory Drugs (NSAIDS) and Ulcers

What are nonsteroidal anti-inflammatory drugs (NSAIDs)?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for the inflammation of arthritis and other body tissues, such as in tendinitis and bursitis. The are also used for minor aches and pain.
Examples of NSAIDs include:

• aspirin,
• indomethacin (Indocin),
• ibuprofen (Motrin),
• naproxen (Naprosyn),
• piroxicam (Feldene),
• nabumetone (Relafen), and
• Celecoxib (Celebrex).

NSAIDs are available by prescription or without a prescription (over-the-counter). They are also ingredients in many over the counter medications used for colds and minor aches and pain. They are administered orally as capsules, tablets, liquids, or by injection ketorolac (Toradol). Although not included in this review, NSAIDs are also used as eye drops for eye inflammation (for example, ketorolac tromethamine [Acular]).
NSAIDs are taken regularly by approximately 33 million Americans and over 30 billion doses of NSAIDs are consumed annually in the United States.

What are side effects of NSAIDs?

The major side effects of NSAIDs are related to their effects on the stomach and bowels (gastrointestinal system). Some 10%-50% of patients are unable to tolerate NSAID treatment because of side effects, including abdominal pain, diarrhea, and upset stomach. Approximately 15% of patients on long-term NSAID treatment develop a peptic ulcer (ulceration of the stomach or duodenum). Even though many of these patients with ulcers do not have symptoms and are unaware of their ulcers, they are at risk of developing serious ulcer complications such as bleeding or perforation of the stomach.
The annual risk of serious complications is 1%-4% with chronic NSAID treatment. The risk of ulcers is higher in elderly patients, in those with rheumatoid arthritis, patients taking blood thinning medications (anticoagulants) such as warfarin (Coumadin) and heparin) or steroid-containing medications (for example, prednisone), and patients with a prior history of bleeding ulcers. (The anticoagulants do not cause NSAID related ulcers. Rather they increase bleeding if NSAID-induced ulcers occur.)
Prior history of ulcers is the most important predictor of NSAID-induced ulcers. Patients with heart disease who are taking aspirin for prevention of heart attacks are also at risk, and the risk of bleeding ulcers doubles if aspirin is combined with other NSAIDs.

How do NSAIDs work and how do they cause stomach problems?

Prostaglandins are natural chemicals that serve as messengers to promote inflammation. By inhibiting the body's production of prostaglandins, NSAIDs decrease inflammation and the symptoms and signs of inflammation, pain, tenderness, and fever. However, certain prostaglandins also are important in protecting the stomach lining from the corrosive effects of stomach acid as well as playing a role in maintaining the natural, healthy condition of the stomach lining. These protective prostaglandins are produced by an enzyme called Cox-1. By blocking the Cox-1 enzyme and disrupting the production of prostaglandins in the stomach, NSAIDs can cause ulcers and bleeding. Some NSAIDs have less effect on prostaglandins in the stomach than others, and, therefore, may have a lower risk of causing ulcers but the increased risk of ulcers still exists.

If a stomach ulcer is detected, how is it treated?

Treatment of NSAID-induced ulcers involves discontinuing the NSAID, reducing stomach acid with H2-blockers, for example, ranitidine (Zantac), cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid, Axid AR), or, more effectively, with proton pump inhibitors, such as omeprazole (Prilosec) or synthetic prostaglandins, specifically misoprostol (Cytotec). Since H. pylori bacteria is a common cause of ulcers, eradication of the bacteria with a combination of antibiotics may also promote ulcer healing.

Can NSAID-related ulcers and complications be prevented?

NSAIDs are valuable medications for patients with arthritis and other inflammatory conditions. For patients who need long-term NSAID treatment, several steps can be taken to decrease NSAID-related ulcers and complications. The risk of ulcers and complications tend to be dose related. Therefore, the smallest effective dose of NSAIDs is taken to minimize the risk. NSAIDs might be selected that have less effect on the stomach production of prostaglandins. Some of these NSAIDs are called selective Cox-2 inhibitors. Cox-2 inhibitors block the Cox-2 enzyme that produces prostaglandins of inflammation without blocking the natural prostaglandin production of Cox-1 in the stomach. Currently in the U.S., the only available Cox-2 inhibitor is celecoxib (Celebrex).
Taking NSAIDs with meals may minimize stomach upset with NSAIDs but not ulcerations.
A synthetic prostaglandin, misoprostol (Cytotec), can be administered orally along with NSAIDs. Misoprostol has been shown to decrease NSAID-induced ulcers and their complications. The side effects of misoprostol include abdominal cramps and diarrhea. Misoprostol is also avoided in pregnant women because it can cause uterine muscle contractions and miscarriage. Standard doses of H2-blockers and proton pump inhibitors reduce the risk of NSAID-induced ulcers.
Scientists are actively searching for safer NSAIDs that are effective anti-inflammatory agents but are not ulcer producing. In the meantime, patients who need long term NSAID treatment should be closely supervised by a doctor. Patients at risk of NSAID-induced ulcers and complications should consider preventive measures, such as using NSAIDs with less prostaglandin disrupting effects on the stomach and using proton pump inhibitors, H2-blockers, or misoprostol. Stopping smoking, and eradicating H. pylori may also be helpful since both smoking and infection with H. pylori themselves cause ulcers.

Fibrocystic Breast Condition Fibrocystic Changes

What are fibrocystic breasts?

Fibrocystic breasts are characterized by lumpiness and usually discomfort in one or both breasts. The lumpiness is due to small breast masses or breast cysts. The condition is very common and benign, meaning that fibrocystic breasts are not malignant (cancerous). Fibrocystic breast disease (FBD), now referred to as fibrocystic changes or fibrocystic breast condition, is the most common cause of "lumpy breasts" in women and affects more than 60% of women. The condition primarily affects women between the ages of 30 and 50, and tends to become less of a problem after menopause.
The diagnosis of fibrocystic breasts is complicated by the fact that the condition can vary widely in its severity. In some women, the symptoms of fibrocystic breast condition can be very mild with minimal breast tenderness or pain. The symptoms can also be limited in time, usually occurring only premenstrually. It may not even be possible to feel any lumps when the breasts are examined by the woman herself or by her doctor. In other women with fibrocystic breasts, the painful breasts and tenderness are constant, and many lumpy or nodular areas can be felt throughout both breasts.

Picture of the anatomy of the breast

 

Is there a difference between fibrocystic breast condition and fibrocystic breast disease?

No. In the past, fibrocystic breast condition was often called fibrocystic breast disease. However, it is not a disease, but a condition. Most women tend to have some lumpiness in their breasts. Therefore, it is now being more appropriately termed fibrocystic breast condition. The abbreviation is FCC (an acronym derived from FibroCystic breast Condition).
Other names that have been applied to fibrocystic breast condition include mammary dysplasia, chronic cystic mastitis, diffuse cystic mastopathy, and benign breast disease (a term that includes other benign breast disorders, including infections).

What causes fibrocystic breasts?

Fibrocystic breast condition involves the glandular breast tissue. The sole known biologic function of these glands is the production, or secretion, of milk. Occupying a major portion of the breast, the glandular tissue is surrounded by fatty tissue and support elements. The glandular tissue is composed of different types of cells: (1) clusters of secretory cells (cells that produce milk) that are connected to the milk ducts (tiny tubes); and (2) the cells that line the surfaces of the secretory cells, called the epithelial cells.
The most significant contributing factor to fibrocystic breast condition is a woman's normal hormonal variation during her monthly cycle. Many hormonal changes occur as a woman's body prepares each month for a possible pregnancy. The most important of these hormones are estrogen and progesterone. These two hormones directly affect the breast tissues by causing cells to grow and multiply.
Many hormones aside from estrogen and progesterone also play an important role in causing fibrocystic breasts. Prolactin, growth factor, insulin, and thyroid hormone are some of the other major hormones that are produced outside of the breast tissue, yet act in important ways on the breast. In addition, the breast itself produces hormonal products from its glandular and fat cells. Signals that are released from these hormonal products are sent to neighboring breast cells. The signals from these hormone-like factors may, in fact, be the key contributors to the symptoms of fibrocystic breast condition. These substances may also enhance the effects of estrogen and progesterone and vice versa.
The same cyclical hormones that prepare the glandular tissue in the breast for the possibility of milk production (lactation) are also responsible for a woman's menstrual period. However, there is a major difference between what happens in the breast and uterus.
In the uterus (the womb), these hormones promote the growth and multiplication of the cells lining the uterus. If pregnancy does not occur, this uterine lining is sloughed off and discharged from a woman's body during menstruation.
In the breast, these same hormones stimulate the growth of breast glandular tissue and increase the activity of blood vessels, cell metabolism, and supporting tissue. All this activity may contribute to the feeling of breast fullness and fluid retention that women commonly experience before their menstrual period.
When the monthly cycle is over, however, these stimulated breast cells cannot simply slough away and pass out of the body like the lining of the uterus. Instead, many of these breast cells undergo a process of programmed cell death, called apoptosis. During apoptosis, enzymes are activated that start digesting cells from within. These cells break down and the resulting cellular fragments are then further broken down by scavenger cells (inflammatory cells) and nearby glandular cells.
During this process, the fragments of broken cells and the inflammation may lead to scarring (fibrosis) that damages the ducts and the clusters (lobules) of glandular tissue within the breast. The inflammatory cells and some of the breakdown fragments may release hormone-like substances that in turn act on the nearby glandular, ductal, and structural support cells.
The amount of cellular breakdown products, the degree of inflammation, and the efficiency of the cellular cleanup process in the breast vary from woman to woman. These factors may also fluctuate from month to month in an individual woman. They may even vary in different areas of the same breast in a woman.

Why is it important to diagnosis fibrocystic breasts?

The basic problem with fibrocystic breast condition is the threat of breast cancer. Fibrocystic breast condition is itself benign (non-cancerous) and exceedingly common. Additionally, breast cancer is a common malignancy in women. Both conditions, one benign and the other a leading cause of cancer deaths in women, involve the same organ - the breast, and both can involve the presence of breast masses.
Fibrocystic lumps in the breast can closely mimic those found in breast cancer. They can also sometimes make breast cancer difficult to detect. Therefore, fibrocystic breast condition often makes both the patient and her physician quite concerned about the possibility of breast cancer. If a woman's breasts are fibrocystic, diagnostic tests in addition to screening mammography may be necessary in order to rule out an underlying breast cancer.

Trisomy 18 (Edwards Syndrome)

Trisomy 18 facts

• Trisomy 18 (Edwards syndrome) results from the presence of an extra copy of chromosome 18.
• Trisomy 18 leads to severe intellectual and physical defects.
• The prognosis of trisomy 18 is poor; half of those affected do not live beyond the first week of life and only 10% of infants with this condition live beyond the first year.
• Common features of trisomy 18 include a low birth weight; a small jaw and mouth; an abnormally shaped, small head; overlapping fingers and clenched fists; and defects in the heart and other organs.
• Trisomy 18 occurs on average in 1 out of every 6,000 births.
• Up to 95% of fetuses with trisomy 18 die in the prenatal period (prior to delivery).
• Girls are affected more commonly than boys.

What is trisomy 18?

Trisomy 18, also known as Edwards Syndrome, is a severe genetic disorder associated with intellectual disability and abnormalities in many organs. Trisomy 18 was first described in 1960 and results from an additional copy of chromosome 18 (normal cells carry two copies of each chromosome; the term, "trisomy," refers to the presence of three of a given chromosome). Only about 10% of affected infants survive past one year of age, and half of affected infants do not live beyond the first week of life.

What are the chromosome basics of trisomy 18?

In most cases of trisomy 18, all the cells in the body have an extra copy of chromosome 18. Around 5% of affected people have the extra chromosome 18 in some, but not all, of the body's cells. This phenomenon is known as mosaic trisomy 18. Mosaic trisomy 18 may be very severe or hardly noticeable, depending upon the number of cells that have the extra chromosome.
In rare cases, there is no extra chromosome present; rather, a portion of the long arm of chromosome 18 becomes attached to another chromosome during the formation of egg and sperm cells or very early in development of the embryo. In this case, the individual has two copies of chromosome 18 plus the additional material from chromosome 18 that is attached to another chromosome. This is known as translocation, and the extra genetic material causes the developmental abnormalities in the same way as the presence of an entire extra chromosome. The signs and symptoms of this form of trisomy 18 are dependent upon the amount of chromosomal material that was translocated to another chromosome.
Trisomy 18 is not an inherited condition; it occurs as the result of random events during egg and sperm formation. The type of error that occurs is known as nondisjunction, and this leads to an egg or sperm cell with an abnormal number of chromosomes.
It is not known precisely why the extra genetic material causes the abnormalities specific to trisomy 18. As with Down syndrome (trisomy 21), experts believe that the presence of the extra chromosomal material interferes with the expression and interaction of various genes, resulting in impaired development and function.

What are the characteristic signs and symptoms of trisomy 18?

Common birth defects in infants with trisomy 18 include a low birth weight; a small jaw and mouth; an abnormally shaped, small head; overlapping fingers and clenched fists; “rocker-bottom” feet; low-set ears; and defects in the heart and other organs. Surviving infants may display poor feeding, respiratory problems, delayed growth, and other life-threatening complications. Mental impairment is also characteristic of this syndrome.

How common is trisomy 18?

Trisomy 18 occurs on average in 1 out of every 6,000 babies. Girls are affected far more commonly than boys; about 80% of affected infants are female. Any woman can have a child with trisomy 18, but the risk increases with increasing maternal age.

How is trisomy 18 diagnosed?

In newborns, chromosome analysis can be carried out to determine the exact cause of birth defects. Prenatal testing for trisomy 18 is possible.
Screening tests such as measurement of alpha fetoprotein (AFP) levels (sometimes referred to as a triple screen) is one screening test. The triple test screens the mother's blood for AFP, hCG (human chorionic gonadotropin, the so-called “pregnancy hormone”), and estriol (a type of estrogen). The test is performed between the 15th and 17th week of pregnancy. A positive result on a screening test does not mean that the baby will have trisomy 18 or any chromosomal abnormality. In fact, only about 11% of those women who receive a positive result for trisomy 18 in this test will actually have an affected fetus.
Ultrasound is another commonly used screening test. Like the AFP test, a simple ultrasound cannot be used to establish the diagnosis of trisomy 18. A more detailed ultrasound may be performed to look for the characteristic signs of trisomy 18, but it cannot confirm alone that trisomy 18 is present.
Analysis of fetal chromosomal material obtained during amniocentesis or chorionic villus sampling is necessary to prove that the additional copy of chromosome 18 is present. An amniocentesis is usually performed at 15-18 weeks of pregnancy and is the most commonly used test for the prenatal diagnosis of trisomy 18. During this procedure, a thin needle is inserted through the abdominal wall and a small sample of amniotic fluid is taken.
Chorionic villus sampling is another type of test that allows the examination of fetal genetic material. It is performed earlier in pregnancy (at 10-12 weeks after the last menstrual period) and therefore carries the advantage of allowing for an earlier diagnosis. This procedure involves the collection a chorionic villus cell sample from the placenta either through the insertion of a needle in the abdominal wall or through a catheter in the vagina.

Can people with trisomy 18 survive to adulthood?

Survival to adulthood is extremely rare in trisomy 18. However, a few reports have described individuals who survived to the teen or early adult years. These young adults require supportive caregiving and are not able to live independently.

Is there any treatment for trisomy 18?

Treatment for trisomy 18 is supportive, meaning that the condition cannot be cured, and treatments are directed at prolonging survival and managing complications. Common treatment measures include nutritional support, treatment of infections, transfusions for low blood cell counts, and medications such as diuretics and/or digoxin to manage heart failure. Heart failure and pneumonia are common causes of death in people with trisomy 18.

Sciatica

Sciatica facts

• Sciatica is nerve pain from irritation of the sciatic nerve.
• The sciatic nerve is the largest nerve in the body.
• Sciatica pain is typically felt from the low back to behind the thigh and radiating down below the knee.
• Treatments for sciatica depend on the underlying cause and the severity of the pain.

What is sciatica?

Sciatica is pain in the lower extremity resulting from irritation of the sciatic nerve. The pain of sciatica is typically felt from the low back (lumbar area) to behind the thigh and radiating down below the knee. The sciatic nerve is the largest nerve in the body and begins from nerve roots in the lumbar spinal cord in the low back and extends through the buttock area to send nerve endings down the lower limb. The pain of sciatica is sometimes referred to as sciatic nerve pain.

What are causes of sciatica?

While sciatica is most commonly a result of a lumbar disc herniation directly pressing on the nerve, any cause of irritation or inflammation of the sciatic nerve can reproduce the symptoms of sciatica. This irritation of nerves as a result of an abnormal intervertebral disc is referred to as radiculopathy. Aside from a pinched nerve from a disc, other causes of sciatica include irritation of the nerve from adjacent bone, tumors, muscle, internal bleeding, infections, injury, and other causes. Sometimes sciatica can occur because of irritation of the sciatic nerve during pregnancy.

Picture of a herniated disc, a common cause of sciatica 

What are risk factors for sciatica?

Risk factors for sciatica include degenerative arthritis of the lumbar spine, lumbar disc disease, and trauma or injury to the lumbar spine.

What are sciatica symptoms?

Sciatica causes pain, a burning sensation, numbness, or tingling radiating from the lower back and upper buttock down the back of the thigh to the back of the leg. The result is lumbar pain, buttock pain, hip pain, and leg pain. Sometimes the pain radiates around the hip or buttock to feel like hip pain. While sciatica is often associated with lower back pain (lumbago), it can be present without low back pain. Severe sciatica can make walking difficult if not impossible. Sometimes the symptoms of sciatica are aggravated by walking or bending at the waist and relieved by lying down. The pain relief by changing positions can be partial or complete.

How is sciatica diagnosed?

Sciatica is diagnosed with a physical exam and medical history. The typical symptoms and certain examination maneuvers help the health care professional to diagnose sciatica. Sometimes, X-rays and other tests, such as CT scan, MRI scan, and electromyogram, are used to further define the exact causes of sciatica.

What are treatment options for sciatica?

Bed rest has been traditionally advocated for the treatment of acute sciatica. But how useful is it?
To study the effectiveness of bed rest in patients with sciatica of sufficient severity to justify treatment with bed rest for two weeks, a research team in the Netherlands led by Dr. Patrick Vroomen randomly assigned 183 such patients to bed rest or, alternatively, to watchful waiting for this period.
To gauge the outcome, both primary and secondary measures were examined. The primary outcome measures were the global assessments of improvement after two and 12 weeks by the doctor and the patient. The secondary outcome measures were changes in functional status and in pain scores, absenteeism from work, and the need for surgical intervention. Neither the doctors who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments.
The results, reported in the New England Journal of Medicine, showed that after two weeks, 64 of the 92 (70%) patients in the bed-rest group reported improvement, as compared with 59 of the 91 (65%) of the patients in the control (watchful-waiting) group. After 12 weeks, 87% of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the aggravation of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups.
The researchers concluded that "among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting." Sometimes, conventional wisdom is not as wise as research!
Other treatment options for sciatica include addressing the underlying cause, medications to relieve pain and inflammation (including oral and injectable cortisone) and relax muscles, and physical therapy. A variety of low back conditioning and stretching exercises are employed to help people recover from sciatica. Surgical procedures can sometimes be required for persisting sciatica that is caused by nerve compression at the lower spine. Sometimes pain management specialists help with chronic sciatica conditions.

What is the outlook (prognosis) for patients with sciatica?

Depending on the precise cause of the sciatica and the duration of symptoms, the outlook for recovery from sciatica ranges from excellent to having long-term chronic symptoms.

Can sciatica be prevented?

Sciatica can be prevented only to the extent that low back trauma injuries can be avoided can sciatica.

Reflex Sympathetic Dystrophy (RSD, Complex Regional Pain Syndrome, CRPS)

Reflex sympathetic dystrophy (RSD) facts

• Reflex sympathetic dystrophy (RSD) is characterized by a group of symptoms including pain (often "burning" type), tenderness, and swelling of an extremity associated with varying degrees of sweating, warmth and/or coolness, flushing, discoloration, and shiny skin.
• How RSD occurs is not known, but there are often triggering events.
• Symptoms of RSD often occur in three stages: 1) acute, 2) dystrophic, and 3) atrophic.
• Diagnosis of RSD is based on clinical findings, supported by radiological tests.
• Treatment of RSD is most effective in the earlier stages.

What is reflex sympathetic dystrophy (RSD)?

Reflex sympathetic dystrophy (RSD) is a condition that features a group of typical symptoms, including pain (often "burning" type), tenderness, and swelling of an extremity associated with varying degrees of sweating, warmth and/or coolness, flushing, discoloration, and shiny skin. RSD is also referred to as "complex regional pain syndrome," "the shoulder-hand syndrome," "causalgia," and "Sudeck's atrophy."

What causes reflex sympathetic dystrophy (RSD)?

The exact mechanism of how RSD develops is poorly understood. The theories include irritation and abnormal excitation of nervous tissue, leading to abnormal impulses along nerves that affect blood vessels and skin. The involuntary nervous system, peripheral nerves, and brain seem to be involved.
A variety of events can trigger the RSD, including:

• injury,
• surgery,
• heart disease,
• degenerative arthritis of the neck,
• stroke or other brain diseases,
• nerve irritation by entrapment (such as carpal tunnel syndrome),
• shingles,
• shoulder problems,
• breast cancer, and
• drugs for tuberculosis and barbiturates.

There is no associated or identified inciting event in one-third of individuals with RSD. Fibromyalgia has been reported to coexist with RSD in some people.

What are the symptoms of reflex sympathetic dystrophy (RSD)?

The onset of RSD symptoms may be rapid or gradual. The condition may not display all features. It is bilateral (involving both sides of the body) in up to half of people with RSD. There are several stages of RSD with symptoms that include:

1. Acute (three to six months): burning, flushing, blanching, sweating, swelling, pain, and tenderness. This stage can show early X-ray changes of patchy bone thinning.
2. Dystrophic (three to six months): early skin changes of shiny, thickened skin and contracture with persistent pain, but diminished swelling and flushing.
3. Atrophic (may be long-standing): loss of motion and function of the involved hand or foot with contracture (flexed scarring process), and thinning of the fatty layers under the skin. X-ray can show significant osteoporosis.
   

   How is reflex sympathetic dystrophy (RSD) diagnosed?

   RSD is diagnosed based on the clinical features described previously. Blood tests are not abnormal because of RSD, though the associated triggering events mentioned previously may lead to abnormalities in laboratory testing. Plain film X-ray testing and MRI scanning can show patchy thinning or significant osteoporosis. Nuclear bone scanning can show characteristic uptake patterns.
   
   

   What is the treatment for reflex sympathetic dystrophy (RSD)?

   Response to treatment of RSD is greater in the earlier stages of the condition than in the later stages.
   
4. Cool, moist applications to the affected areas can provide some relief of burning symptoms.
5. Gradual exercise can help prevent contractures.
6. Medications for pain and inflammation can also reduce symptoms.
7. For persisting symptoms, high doses of prednisone (cortisone) may be used for periods of weeks, depending on the response, and then gradually reduced.
8. Other medications that may be of benefit include amitriptyline (Elavil, Endep), pregabalin (Lyrica), and clonidine (Catapres, Catapres=TTS, Jenloga).
9. Occasionally, a nerve block with anesthetic injected into a specialized area of the involuntary nervous system (for example, a stellate ganglion blockade) can help both in treatment and in establishing the diagnosis. Sometimes a series of these blocks is tried.
10. Other treatments include surgically interrupting the nerves (the sympathetic nerves) of the involuntary nervous system (surgical sympathectomy), implanting pumps with pain medication into the spinal canal (intrathecal drug pumps), and spinal cord stimulation devices.

1. What is the prognosis for reflex sympathetic dystrophy (RSD)

   The prognosis (outlook) and response to treatment in patients with RSD is unpredictable. As previously mentioned, instituting treatment early in the course of the condition leads to better outcomes.
   
   

   Can reflex sympathetic dystrophy (RSD) be prevented?

   There is some evidence that early immobilization of patients with stroke or heart attack can help decrease the chances of developing RSD. Also, there have been studies demonstrating a decrease in the risk of developing RSD in patients with bony fractures using daily Vitamin C supplementation.