Related Terms

• Abrasions, anal fissure, autolytic debridement, bed sore, Clostridium sp., collagen, collagen matrix, cuts, debridement, decubitus ulcer, diabetic ulcers, electrotherapy, epithelial, epithelialization phase, extravasation, gangrene, gas gangrene, human growth factors, hydrocolloid, hyperbaric oxygen, incision wounds, incontinence, infected surgical wounds, infectious arthritis, inflammatory phase, injuries, laceration, macrophages, mechanical debridement, microvascular, minor injuries, myonecrosis, necrotizing fasciitis, pressure ulcers/wound care, proliferative phase, puncture wound, remodeling phase, scrapes, scratches, sepsis, septic arthritis, skin damage caused by incontinence, skin graft healing (split thickness), skin ulcer, surgical skin flap ischemia, skin wounds, squamous, stitches, superficial, suture, vulnerary, wound care, wound healing.

Background

• A wound is a break in the outer layer of the skin, called the epidermis. Wounds are usually caused by cuts or scrapes. Different kinds of wounds may be treated differently from one another, depending upon how they happened and how serious they are. Other wounds include puncture wounds, lacerations (cuts), pressure sores, anal fissures, extravasations (a drug accidentally going outside of a vein causing tissue damage), skin damage caused by incontinence (lack of bladder control), skin graft healing (split thickness), diabetic ulcers, and surgical skin flap ischemia (lack of blood flow to surgically attached skin).

• Healing is a response to the injury that sets into motion a sequence of events. With the exception of bone, all tissues heal with some external scarring. The object of proper care is to minimize the possibility of infection and scarring.

• There are basically four phases to the healing process: the inflammatory phase, proliferative phase, remodeling phase, and epithelialization phase.

• The inflammatory phase begins with the injury itself. In the inflammatory phase, there is bleeding, immediate narrowing of the blood vessels, clot formation, and release of various chemical substances into the wound that will begin the healing process. Specialized cells (macrophages) clear the wound of debris over the course of several days.

• Next is the proliferative phase in which a matrix or latticework of cells forms. On this matrix, new skin cells and blood vessels will form. It is the new small blood vessels (known as capillaries) that give a healing wound its pink or purple-red appearance. These new blood vessels will supply the rebuilding cells with oxygen and nutrients to sustain the growth of the new cells and support the production of proteins (primarily collagen). The collagen acts as the framework upon which the new tissues build. Collagen is the dominant substance in the final scar.

• The remodeling phase begins after 2-3 weeks. The framework (collagen) becomes more organized making the tissue stronger. The blood vessel density becomes less, and the wound begins to lose its pinkish color. Over the course of six months, the area increases in strength, eventually reaching 70% of the strength of uninjured skin.

• Epithelialization is the process of laying down new skin, or epithelial, cells. The skin forms a protective barrier between the outer environment and the body. Its primary purpose is to protect against excessive water loss and bacteria. Reconstruction of this layer begins within a few hours of the injury and is complete within 24-48 hours in a clean, sutured (stitched) wound. Open wounds may take 7-10 days because the inflammatory process is prolonged, which contributes to scarring. Scarring occurs when the injury extends beyond the deep layer of the skin (into the dermis, which is the second layer of skin).

Causes and Risk Factors

• Minor wounds:

• Minor wounds include cuts, scrapes, scratches, and punctured skin. They often occur as a result of an accident or injury, but surgical incisions, sutures, and stitches also cause wounds. Minor wounds usually are not serious, but even cuts and scrapes require care.

• Scrapes and abrasions are superficial (on the surface). The deeper skin layers are intact, and bleeding is slow and oozing. Scrapes and abrasions are usually caused by friction or rubbing against an abrasive surface.

• Lacerations (cuts) go through all layers of the skin and into the fat or deeper tissues. Bleeding may be more brisk or severe. Severe blows by a blunt object, falls against a hard surface, or contact with a sharp object are the most common causes of lacerations.

• Puncture wounds are generally caused by a sharp pointed object entering the skin. Most common examples are stepping on a nail or getting stuck with a needle or a tack. Bleeding is usually minimal, and the wound may be barely noticeable.

• Human bites and animal bites can be puncture wounds, lacerations, or a combination of both. These wounds are always contaminated by saliva and require extra care.

• Pressure (decubitus) ulcers:

• A pressure (decubitus) ulcer, also known as a bedsore, is an area of skin that breaks down when an individual stays in one position for too long without shifting their weight. This often happens if an individual uses a wheelchair or if they are bedridden, even for a short period of time (such as after surgery or an injury). Constant pressure against the skin reduces the blood supply to that area, and the affected tissue dies.

• A pressure ulcer starts as reddened skin but gets progressively worse, forming a blister, then an open sore, and finally a crater. The most common places for pressure ulcers are over bony prominences (bones close to the skin) like the elbow, heels, hips, ankles, shoulders, back, and the back of the head. Pressure ulcers occur in approximately 9% of hospitalized patients, usually during the first two weeks of hospitalization, and in approximately one fourth of nursing home residents.

• Risk factors for developing a pressure ulcer include:

• Age: The majority of pressure sores occur in people older than 70. Older adults tend to have thinner skin than younger people do, making them more susceptible to damage from minor pressure. Elderly individuals also tend to be underweight, with less natural cushioning over their bones. And poor nutrition, a serious problem among older adults, not only affects the integrity of the skin and blood vessels but also hinders wound healing. Even with optimum nutrition and good overall health, wounds tend to heal more slowly as individuals age. Also, nursing home residents have higher rates of bedsores than do people who are hospitalized or cared for at home due to immobilization and urinary incontinence.

• Lack of pain perception: Individuals with a loss of sensation, such as in spinal cord injuries or disease, cannot feel discomfort or the need to change positions when a bedsore is forming.

• Malnutrition: Individuals are more likely to develop pressure sores if they have a poor diet, especially one deficient in protein, zinc, and vitamin C. Individuals that are lacking in nutrition are also more likely to have recurrent pressure sores, more severe infections, and slower healing wounds than are people with healthier diets.

• Urinary or fecal incontinence: Problems with bladder control can greatly increase the risk of pressure sores because the skin stays moist, making it more likely be damaged. Bacteria from fecal matter not only can cause serious local infections but also lead to life-threatening systemic complications such as sepsis, gangrene and, rarely, necrotizing fasciitis (a severe and rapidly spreading infection).

• Conditions affecting circulation: Because certain health problems, such as diabetes and vascular disease, affect circulation, parts of the body may not receive adequate blood flow increasing an individual's risk of tissue damage.

• Smoking: Smokers have a higher incidence of pressure sores than nonsmokers. Smokers also tend to develop more severe wounds and to heal more slowly, mainly because nicotine impairs circulation and reduces the amount of oxygen in the blood. The risk increases with the number of years and cigarettes smoked.

• Decreased mental awareness: Individuals whose mental awareness is lessened by disease, trauma, or medications are often less able to take the actions needed to prevent or care for pressure sores.

• Diabetic ulcer:

• According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD), an estimated 18 million Americans (6.3% of the population) are known to have diabetes, and millions more are considered to be at risk. Of those at risk, diabetes is undiagnosed in 5.2 million. Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes. Among patients with diabetes, 15% will develop a foot ulcer, and 12-24% of those with a foot ulcer will require amputation. Diabetic ulcers are the most common foot injuries leading to lower extremity amputation in the United States, accounting for 60% of these amputations.

• Diabetic peripheral neuropathy (nerve damage as a result of diabetes) causes the greatest risk of foot ulceration, due to microvascular (small blood vessels) disease and uncontrolled blood sugar levels. Peripheral neuropathy disables sensation in the feet so the individual is unable to sense pain or discomfort if injured in that area. This allows the injury to be left untreated, increasing the risk of a more severe wound (ulcer) with infection.

• Other wounds:

• Anal fissure: An anal fissure is a small tear in the lining of the anal canal. Anal fissures are common in infants ages six to 24 months, and anal fissures are less likely to develop in older children. Adults may develop anal fissures as a result of passing hard or large stools during bowel movements.

• Anal fissures may cause pain and bleeding. More than 90% of anal fissures heal on their own. Individuals can use topical creams or suppositories to provide relief as they heal. Anal fissures that fail to heal may become chronic and cause considerable discomfort.

• Extravasation: Extravasation injury is a well-known adverse event associated with certain intravenous (IV) drugs, such as chemotherapy. Extravasation occurs when drugs escape from the veins or IV catheters into subcutaneous (subQ) tissues. Accidental extravasation occurs in approximately 0.1-6% of patients receiving intravenous chemotherapy. Cancer patients are inherently at high risk of extravasation due to the fact that they often require multiple puncture sites for IV drugs and have thin and fragile veins. Some have peripheral vascular disease and malnutrition. Certain chemotherapy drugs, such as doxorubicin (Adriamycin®) and daunorubicin (Cerubidine®), are more likely to cause extravasation than others.

Signs and Symptoms

• Skin wounds: All bites and any cut or laceration greater than 1/2-inch long in which fat or deeper tissues (muscle or bone) can be seen will require medical attention.

• Any redness extending from the wound after two days or yellow drainage from the area should warrant medical attention. Infection may cause redness, swelling, heat, pus, or watery discharge from a puncture wound that is not noticed or not treated properly.

• Puncture wounds usually cause pain and mild bleeding at the site of the puncture. It is usually fairly obvious if cut. However, small pieces of glass may cause puncture wounds that the individual may not notice at first.

• Most doctors will not stitch a cut or laceration that is more than eight to 12 hours old. This is because there is a greater chance of infection after that time. In fact, after three hours, the incidence of infection begins to increase. Therefore, do not wait to have the injury repaired. If in doubt, call a doctor or go to the nearest hospital's emergency department. An open wound takes longer to heal and leaves a bigger scar.

• Healthcare providers recommend that 911 be called if: the wound is obviously life-threatening; any laceration is greater than 1/2-inch long and is through all layers of the skin exposing the underlying fat; the bleeding cannot be stopped; if the blood continues to spurt from the wound. Apply pressure and go to the hospital's emergency department: if there may be something in the wound such as glass, wood, or rust; if the individual cannot move their fingers or toes in the area of the laceration or if they have lost sensation in the area beyond the laceration; and for any bite wound (human or animal).

• Pressure sores: Bedsores fall into one of four stages based on their severity. Pressure sores are categorized by severity, from Stage I (earliest signs) to Stage IV (worst). The National Pressure Ulcer Advisory Panel, a professional organization dedicated to the prevention and treatment of pressure sores, has defined each stage as follows:

• Stage I: Initially, a pressure sore appears as a persistent area of red skin that may itch or hurt and feel warm and spongy or firm to the touch. In African Americans, Hispanics, and people with darker skin, the mark may appear to have a blue or purple cast, or look flaky or ashen. Stage I wounds are superficial and go away shortly after the pressure is relieved.

• Stage II: In stage II, some skin loss has already occurred, either in the epidermis, the outermost layer of skin, in the dermis, the skin's deeper layer, or in both. The wound is now an open sore that looks like a blister or an abrasion, and the surrounding tissues may show red or purple discoloration. If treated promptly, stage II sores usually heal fairly quickly.

• Stage III: When a pressure ulcer reaches stage III, the damage has extended to the tissue below the skin, creating a deep, crater-like wound.

• Stage IV: Stage IV is the most serious and advanced stage. The pressure ulcer has become so deep that there is damage to the muscle and bone, and sometimes tendons and joints. Stage IV wounds are extremely difficult to heal and can lead to lethal infections.

• If an individual uses a wheelchair, they are most likely to develop a pressure sore on: the tailbone or buttocks; the shoulder blades and spine; or the backs of the arms and legs where they rest against the chair. When an individual is bed-bound, pressure sores can occur on: the back or sides of the head; the rims of the ears; the shoulders or shoulder blades; the hipbones, lower back, or tailbone; or the backs or sides of the knees, heels, ankles, and toes.

• Anal fissure: The main signs and symptoms of an anal fissure include: pain or burning during bowel movements that eases until the next bowel movement; bright red blood on the outside of the stool or on toilet paper or wipes after a bowel movement; and itching or irritation around the anus.

• Extravasation: During extravasation, the individual will feel burning, stinging, or pain at the injection site. Redness or swelling may be observed at the site of injection. Also, there may be no blood return in the syringe when the healthcare worker tries to get blood.

Complications

• Complications from a lack of wound care can lead to other health problems.

• Cellulitis: Cellulitis is a potentially serious bacterial infection of the skin. Cellulitis appears as a swollen, red area of skin that feels hot and tender, and it may spread rapidly. Skin on the face or lower legs is most commonly affected by this infection, though cellulitis can occur on any part of the body. Cellulitis may only affect the surface of the skin. However, cellulitis may also affect the tissues underlying skin and can spread to lymph nodes and the bloodstream. Left untreated, the spreading bacterial infection may rapidly turn into a life-threatening condition.

• Bone and joint infections: Bone and joint infections develop when the infection from a bedsore burrows deep into the joints and bones. Joint infections (called septic or infectious arthritis) can damage cartilage and tissue within days, whereas bone infections (osteomyelitis) may develop over years if not treated. Eventually, bone infections can lead to bone death, reduced function of the joints and limbs, and amputation.

• Necrotizing fasciitis: Necrotizing fasciitis is a rapidly spreading infection that destroys the layers of tissue that surround the muscles. Initial signs and symptoms include fever, pain, and massive swelling. Without treatment, death can occur in as little as 12-24 hours.

• Gas gangrene (myonecrosis): Gas gangrene is a rare and severe form of gangrene. Gas gangrene develops suddenly and dramatically and spreads so rapidly that changes in tissue are noticeable within minutes. The bacteria responsible for gas gangrene (Clostridium sp.) produce toxins that completely destroy affected muscle tissue and cause potentially fatal systemic problems.

• Sepsis: Sepsis (a whole body response to an infection) can occur from a wound such as advanced pressure sores. Sepsis occurs when bacteria from a massive infection enter the bloodstream and spread throughout the body. Sepsis is a rapidly progressing, life-threatening condition that can cause shock and organ failure.

• Skin cancer: Cancer resulting from poor wound healing may occur. This type of cancer is usually an aggressive carcinoma affecting the skin's squamous cells.

• Fistulas: A fistula is an abnormal connection between an organ, vessel, or intestine and another structure. Fistulas are usually the result of a wound from an injury or surgery. They may also result from infection or inflammation.

Diagnosis

• If a skin injury required medical attention, a doctor will want to know how the injury occurred, what home care was performed, if there is any pain, and when the last tetanus shot may have been.

• If a hand or finger is involved, the doctor will want to make sure the individual is able to move the extremity or finger through its full range of motion. Sensation and circulation to the area will be tested carefully as well. If there is some suspicion of a foreign body in the wound or an underlying bone break, an x-ray may be ordered.

• Pressure sores (bedsores) are usually unmistakable, even in the initial stages, but a doctor is likely to order blood tests to check the individual's nutritional status and overall health. Other tests may include: urine analysis and culture, stool culture, and a wound biopsy. A wound biopsy is a sample of tissue taken from wounds that do not heal or from chronic (long-term) pressure sores. The tissue may also be checked for cancer, which is a risk in individuals with chronic wounds.

Treatment

• General Self-treatment:

• Minor cuts and scrapes usually do not require a trip to the emergency room, yet proper care is essential to avoid infection or other complications. Puncture wounds do not usually cause excessive bleeding. Puncture wounds resulting from human or animal bites, including those of domestic dogs and cats, may be especially prone to infection. Puncture wounds on the foot are also more vulnerable to infection.

• Guidelines developed by healthcare professionals can help individuals care for simple wounds at home. These guidelines include:

• Stopping the bleeding: Minor cuts and scrapes usually stop bleeding on their own. If they do not, apply gentle pressure with a clean cloth or bandage. Hold the pressure continuously for 20-30 minutes. Lifting the pressure to check on bleeding may damage or dislodge the fresh clot that has forming and cause bleeding to resume. If the blood spurts or continues to flow after continuous pressure, seek medical assistance.

• Cleaning the wound: Rinse out the wound with clear water in order to clean the wound. It is best to avoid getting soap into the wound itself, as soap can irritate the wound. If debris remains embedded in the wound after cleaning, see a doctor. Thorough wound cleaning reduces the risk of tetanus. Tetanus (also called lockjaw) is a preventable disease that affects the muscles and nerves, usually due to a contaminated puncture wound.

• To clean the area around the wound, use soap and a washcloth. Hydrogen peroxide, iodine, or an iodine-containing cleanser may irritate living cells. If they are used, do not apply them directly on the wound.

• Medicines: After cleaning the wound, apply a thin layer of an antibiotic cream or ointment such as Neosporin® or Polysporin® to help keep the surface moist. The products do not make the wound heal faster, but they can discourage infection and allow the body's healing process to close the wound more efficiently. Certain ingredients in some ointments can cause a mild rash in some individuals. If a rash appears, stop using the ointment.

• Over-the-counter (OTC) pain relievers such as acetaminophen (Tylenol®) or ibuprofen (Motrin®) are usually sufficient for any pain.

• Doctors recommend getting a tetanus shot every 10 years. If the wound is deep or dirty and the individual's last shot was more than five years ago, a doctor may recommend a tetanus shot booster within 48 hours of the injury.

• Bandaging the wound: Bandages can help keep the wound clean and keep harmful bacteria out. After the wound has healed (three to four days) enough to make infection unlikely, exposure to the air will speed wound healing.

• Dressing change: Change the dressing at least daily or whenever it becomes wet or dirty. If the individual is allergic to the adhesive used in most bandages, switch to adhesive-free dressings or sterile gauze held in place with paper tape, gauze roll, or a loosely applied elastic bandage. A local pharmacy will carry these supplies.

• Stitches: A wound that cuts deeply through the skin or is gaping or jagged-edged and has fat or muscle protruding usually requires stitches. A strip or two of surgical tape may hold a minor cut together, but if the individual cannot easily close the opening of the wound, see a doctor as soon as possible. Proper closure within a few hours minimizes the risk of infection.

• Signs of infection: It is recommended by healthcare professionals to see a doctor if the wound does not heal in a five to seven days or if there is redness, drainage, warmth, or swelling.

• Treatments for specific wounds:

• Animal bites:

• If an animal (especially a stray dog or a wild animal) inflicted the wound, the individual may have been exposed to rabies. A doctor may give antibiotics and suggest initiation of a rabies vaccination series. Report such incidents to county public health officials. If possible, the animal should be confined for ten days of observation by a veterinarian.

• Pressure sores:

• Once a pressure ulcer is identified, steps must be taken immediately to: relieve the pressure on that area. Use pillows, special foam cushions, and sheepskin to reduce the pressure; treat the sore based on the stage of the ulcer. A healthcare provider will give specific treatment and care instructions; avoid further trauma or friction. Powder the sheets lightly to decrease friction in bed; improve nutrition and other underlying problems that may affect the healing process; if the pressure ulcer is at Stage II or worse, a healthcare provider will give specific instructions on how to clean and care for open ulcers. It is very important to do this properly to prevent infection; keep the area clean and free of dead tissue. Generally, pressure ulcers are rinsed with a salt-water rinse to remove loose, dead tissue. The sore should be covered with special gauze dressing made for pressure ulcers. Do not massage the area of the ulcer, as massage can damage tissue under the skin. Donut-shaped or ring-shaped cushions are not recommended. They interfere with blood-flow to that area and cause complications, such as pressure sores.

• Non-surgical treatment: Treating pressure sores is challenging. Open wounds are slow to close, and because skin and other tissues have already been damaged or destroyed, healing is never perfect. Although it may take some time, most stage I and stage II sores will heal with conservative measures. But stage III and stage IV wounds, which are less likely to resolve on their own, may require surgery.

• The first step in treating a sore at any stage is relieving the pressure that caused it. Pressure can be reduced by changing positions often. Carefully follow a schedule for turning and repositioning - approximately every 15 minutes if in a wheelchair and at least once every two hours when in bed. If the individual is unable to change position on their own, a family member or other caregiver must be able to help. Using sheepskin or other padding over the wound can help prevent friction when moving.

• Using support surfaces is important. These are special cushions, pads, mattresses, and beds that relieve pressure on an existing sore and help protect vulnerable areas from further breakdown. The most effective support depends on many factors, including the individual's level of mobility, their body build, and the severity of their wound. Healthcare professionals recommend avoiding using pillows and rubber rings, which actually cause compression.

• Mattresses should be low-air-loss beds or air-fluidized beds. Low-air-loss beds use inflatable pillows for support, whereas air-fluidized beds suspend the individual on an air-permeable mattress that contains millions of silicon-coated beads.

• Other non-surgical treatments of pressure sores include cleaning the wound to prevent infection. A stage I wound can be gently washed with water and mild soap, but open sores should be cleaned with a saltwater (saline) solution each time the dressing is changed. Saline solution is available at a pharmacy, or can be made at home by boiling 1 teaspoon of salt in 1 quart of water for five minutes. Store the solution in a sterile container and cool before using. It is best to avoid antiseptics such as hydrogen peroxide and iodine, which can damage sensitive tissue and delay healing.

• Controlling incontinence as far as possible is crucial to helping sores heal. If the individual is experiencing bladder or bowel problems, they may be helped by lifestyle changes, behavioral programs, incontinence pads, or medications.

• To heal properly, wounds need to be free of damaged, dead, or infected tissue. One approach to removing dead tissue is surgical debridement, a procedure that involves using a scalpel or other instrument to remove dead tissue. Surgical debridement is quick and effective, but it can be painful. A doctor may use one or more non-surgical approaches. These include removing devitalized tissue with a high-pressure irrigation device (mechanical debridement), allowing the body's own enzymes to break down dead tissue (autolytic debridement), or applying topical debriding enzymes, such as Granulex®.

• Dressings: A variety of dressings are used to help protect wounds and speed healing. The type of dressing used usually depends on the stage and severity of the wound. The basic approach, however, is to keep the wound moist and the skin surrounding it dry. Stage I sores may not need any covering, but stage II lesions are usually treated with hydrocolloids, or transparent semi-permeable dressings that retain moisture and encourage skin cell growth. Examples of hydrocolloid dressings include Tegasorb® and Relicare®. Other types of dressings may be more beneficial for weeping wounds or those with surface debris. Contaminated sores may also be treated with a topical antibiotic cream.

• Hydrotherapy: Whirlpool baths can aid healing by keeping skin clean and naturally removing dead or contaminated tissue. Whirlpool baths used for burn treatment are specialized, stainless steel baths used by trained healthcare professionals.

• Healthy diet: Eating a nutritionally rich diet with adequate calories and protein and a full range of vitamins and minerals, especially vitamins A, C, E, and zinc, has been reported to improve wound healing. A well nourished body can produce healthy skin, which guards against breakdown.

• Surgical repair: The goals of surgery include improving the hygiene and appearance of the sore, preventing or treating infection, reducing fluid loss through the wound, and lowering the risk of future cancer. The type of reconstruction that's best in any particular case depends mainly on the location of the wound and whether there's scar tissue from a previous operation. In general, though, most pressure wounds are repaired using a pad of muscle, skin, or other tissue that covers the wound and cushions the affected bone (flap reconstruction). The tissue is usually harvested from the individual's own body. In spite of every precaution, flap reconstruction has one of the highest complication rates of any surgery, and the recovery period is long and arduous. Individuals must have a strong social support system, optimal nutritional status, state-of-the-art resources such as a pressure-release bed, and the ability and motivation to participate in their own recovery to be a candidate for this operation.

• Other treatment options: Hyperbaric oxygen, electrotherapy, and the topical use of human growth factors are methods of wound healing that are being researched. Growth factors, proteins that stimulate cell growth, have been approved for the treatment of diabetic ulcers but not, as yet, for pressure sores.

• Anal fissures:

• Anal fissures are fairly common and usually heal without treatment or with non-surgical treatments. Signs and symptoms may go away within two weeks, but it may take up to eight weeks for the tear to heal. If the tear doesn't heal within six to eight weeks, however, the individual may need surgery.

• For infants, the only intervention necessary may be changing the diaper regularly and keeping the anal area clean. A pediatrician can help provide ways to avoid constipation and ensure regular bowel movements to prevent the baby from straining.

• Non-surgical treatments: Lifestyle and dietary changes include adding more fiber to the diet, drinking more water, getting regular exercise, and taking a stool softener, such as docusate sodium (Colace®). A doctor may recommend non-surgical treatments including medicated creams or suppositories. A doctor may prescribe a rectal corticosteroid (Anusol® or Anusol HC®) or recommend an over-the-counter (OTC) cream or ointment containing hydrocortisone (Preparation H®) to help reduce inflammation and ease discomfort.

• Some doctors recommend applying nitroglycerine ointment (Nitrol® ointment) to the anus, which widens blood vessels and increases blood flow to the tear, promoting healing. This fairly new therapy also helps reduce pressure in the anal sphincter, which eases the spasm and decreases pain, thereby promoting healing. The dose of nitroglycerine is small to avoid dangerous side effects. However, it may cause side effects such as headaches, low blood pressure, and dizziness. Men shouldn't use nitroglycerine within 24 hours of taking erectile dysfunction medications such as sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil (Levitra®) because of the possibility of significantly lowered blood pressure.

• Another fairly new treatment involves injecting a small dose of botulinum toxin type A (Botox®) into the internal anal sphincter. Botox paralyzes the muscle for up to three months, causing the spasm to relax. A possible side effect is temporary, mild leakage of gas or stool (anal incontinence).

• Both topical nitroglycerine and Botox® have shown promise in relieving anal fissures in most studies. Researchers are testing these treatments alone and in combination with other drugs. Blood pressure medications nifedipine (Adalat®) and diltiazem (Cardizem®), taken orally or ground into a gel and applied to the tear, also have shown some promise.

• Surgery: If an individual has a chronic anal fissure that will not heal on its own, a doctor may recommend surgery. Surgery usually involves cutting a portion of the anal sphincter muscle to reduce spasm and pain and promote healing. Surgery may also include removal of the fissure and any scar tissue resulting from it.

• Adults usually have outpatient surgery. Children who have surgery may need to stay overnight in the hospital. Rarely, cutting the anal sphincter results in loss of ability to control bowel movements.

Integrative Therapies

• Unclear or conflicting scientific evidence:

• Aloe: Transparent gel from the pulp of the meaty leaves of Aloe vera has been used topically for thousands of years to treat wounds, skin infections, burns, and numerous other dermatologic conditions. Study results of aloe on wound healing are mixed with some studies reporting positive results and others showing no benefit or potential worsening of the condition. Early studies suggest that aloe may help heal skin ulcers. High-quality studies comparing aloe alone with placebo are needed.

• Avoid if allergic to aloe or other plants of the Liliaceae family (garlic, onions, tulips). Avoid injecting aloe. Do not apply to open skin, surgical wounds or pressure ulcers. Avoid taking by mouth with diarrhea, bowel blockage, intestinal diseases, bloody stools or hepatitis. Avoid with a history of irregular heartbeat (arrhythmia), electrolyte imbalances, diabetes, heart disease or kidney disease. Avoid taking by mouth if pregnant or breastfeeding.

• Alpha-lipoic acid: Alpha-lipoic acid (ALA) may reduce tissue damage that is often caused by long-term exposure to high levels of oxygen. While early studies are promising, more research is needed to fully understand how ALA might work for wound healing in patients undergoing hyperbaric oxygen therapy.

• Avoid if allergic to alpha-lipoic acid (ALA). Use cautiously with diabetes and thyroid diseases. Avoid with thiamine deficiency or alcoholism. Avoid if pregnant or breastfeeding.

• Arginine: Arginine, or L-arginine, is considered a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excess ammonia production, excessive lysine intake, burns, infection, peritoneal dialysis, rapid growth, or sepsis). Arginine has been suggested to improve the rate of wound healing in elderly individuals. A randomized, controlled clinical trial reported improved wound healing after surgery in head and neck cancer patients, following the use of an enteral diet supplemented with arginine and fiber. Arginine has also been used topically (on the skin) to attempt to improve wound healing. Early studies suggest that arginine may also help treat chronic anal fissures. Additional studies are needed.

• Avoid if allergic to arginine, or with a history of stroke, liver, or kidney disease. Avoid if pregnant or breastfeeding. Use caution if taking blood-thinning drugs (like warfarin or Coumadin®) and blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.

• Aromatherapy: Aromatherapy is a technique in which essential oils from plants are used with the intention of preventing or treating illness, reducing stress, or enhancing well-being. Preliminary data from one small study suggests aromatherapy may contribute to reduced pain intensity during dressing changes in wound care. Data are insufficient for forming any opinion for or against this application.

• Essential oils should only be used on the skin in areas without irritation. Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving or operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant.

• Ayurveda: There is some evidence that a traditional Ayurvedic treatment using specially prepared alkaline threads (ksharasutra or Ayurvedic setons) to achieve gradual cauterization may provide an effective alternative to surgery in patients being treated for anal fissures. Further research is needed to confirm these results.

• Ayurvedic herbs should be used cautiously. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs can interact with other herbs, foods and drugs. A qualified healthcare professional should be consulted before taking. Use guggul cautiously with peptic ulcer disease. User should avoid sour food, alcohol and heavy exercise. Mahayograj guggul should not be taken for long periods of time. Pippali (Piper longum) should be taken with milk and avoided with asthma. Avoid sweet flag, and avoid amlaki (Emblica officinalis) at bedtime. Avoid Terminalia hebula (harda) if pregnant. Avoid Ayurveda with traumatic injuries, acute pain, advanced disease stages and medical conditions that require surgery.

• Bovine cartilage: Reduction in inflammation and edema (swelling) and enhancement of the healing of wounds were effects that appeared in the medical literature of bovine cartilage during the 1950s and 1960s. In a preliminary comparison of potential wound healing effects with a commercially available ointment of 10% powdered bovine cartilage (Catrix® 10 Ointment) or Aquaphor® original formula in post-operative facial skin care with a laser resurfacing agent, Catrix® 10 Ointment was better. However, this study was a pilot study so its results need confirmation by follow-up clinical studies that clearly have the appropriate randomization and are double-blinded, given that such were in absence in this study. Also lacking in this study was a definition of primary outcome that therapeutically differentiated Catrix® 10 Ointment.

• Avoid if allergic or hypersensitive to bovine cartilage or any of its constituents. Use cautiously with cancer, renal (kidney) failure, or hepatic (liver) failure. Avoid if pregnant or breastfeeding.

• Calendula: Calendula (Calendula officinalis), also known as pot marigold, has been widely used on the skin to treat minor wounds, skin infections, burns, bee stings, sunburn, warts, and cancer. Calendula is commonly used topically (on the skin) to treat minor skin wounds. Reliable human research is necessary before a firm conclusion can be drawn regarding the use of calendula for wound healing.

• Avoid if allergic to plants in the Aster/Compositae family, such as ragweed, chrysanthemums, marigolds, and daisies. Use cautiously in patients taking sedatives, blood pressure medications, cholesterol medications, blood sugar-altering agents, and immunomodulators. Use cautiously with diabetes and in children. Avoid if pregnant or breastfeeding.

• Chamomile: Chamomile (Matricaria recutita, Chamaemelum nobile) has been used medicinally for thousands of years, and is widely used in Europe. There is promising preliminary evidence supporting the topical use of chamomile for wound healing. However, the available literature is not adequate to support the use of chamomile for this indication.

• Avoid if allergic to chamomile. Anaphylaxis, throat swelling, skin allergic reactions and shortness of breath have been reported. Chamomile eyewash can cause allergic conjunctivitis (pinkeye). Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding.

• Chitosan: There is limited evidence on the effects of chitosan in wound healing. Better studies are needed.

• Avoid if allergic or sensitive to chitosan or shellfish. Use cautiously with diabetes or bleeding disorders. Use cautiously if taking drugs, herbs, or supplements that lower blood sugar or increase the risk of bleeding. Chitosan may decrease absorption of fat and fat-soluble vitamins from foods. Chitosan is not recommended during pregnancy or breastfeeding.

• Dimethylsulfoxide (DMSO): Dimethylsulfoxide (DMSO) is a sulfur-containing organic compound. DMSO occurs naturally in vegetables, fruits, grains, and animal products. DMSO applied to the skin may prevent tissue death after extravasation of anticancer agents. It can be applied alone or with steroids. Limited available study also suggests that DSMO improves lack of blood flow in surgical skin flap ischemia. Currently, there is not enough scientific evidence available for the use of topical DMSO for diabetic ulcers.

• Avoid if allergic or hypersensitive to DMSO. Use caution with urinary tract cancer or liver and kidney dysfunction. Avoid if pregnant or breastfeeding.

• Eucalyptus oil: Eucalyptus (Eucalyptus globulus) oil contains 70-85% 1,8-cineole (eucalyptol), which is also present in other plant oils. Limited evidence suggests that eucalyptus essential oil may be beneficial for patients with skin ulcers when combined with antibiotics. More studies are needed to confirm these early findings.

• Case reports describe allergic rash after exposure to eucalyptus oil, either alone or as an ingredient in creams. Avoid if allergic to eucalyptus oil or with a history of seizure, diabetes, asthma, heart disease, abnormal heart rhythms, intestinal disorders, liver disease, kidney disease, or lung disease. Use caution if driving or operating machinery. Avoid with a history of acute intermittent porphyria. Avoid if pregnant or breastfeeding. A strain of bacteria found on eucalyptus may cause infection. Toxicity has been reported with oral and inhaled use.

• Gotu kola: Gotu kola, Centella asiatica (formerly known as Hydrocotyle asiatica), has a long history of use, dating back to ancient Chinese and Ayurvedic medicine. Preliminary study has demonstrated the ability of Centella asiatica extracts to promote wound healing, possibly through the stimulation of collagen synthesis. However, additional human study is needed in this area.

• Avoid if allergic to gotu kola, asiaticoside, asiatic acid, or madecassic acid. Avoid with a history of high cholesterol, cancer, or diabetes. Avoid if pregnant or breastfeeding.

• Honey: Honey is a sweet, viscid fluid produced by honeybees (Apis melliflera) from the nectar of flowers. The primary studied use of honey is for wound management, particularly in promoting rapid wound healing, deodorizing, and debriding necrotic tissue. The types of wounds studied are varied; most are non-healing wounds such as chronic ulcers, postoperative wounds, and burns. Currently, there is insufficient human evidence to support the use of honey for skin graft healing. Although honey has apparent antibacterial effects, more human study is needed in this area.

• Avoid if allergic or hypersensitive to honey, pollen, celery, or bees. Honey is generally considered safe in recommended doses. Avoid honey from the genus Rhododendron because it may cause a toxic reaction. Avoid in infants younger than 12 months of age. Use cautiously with antibiotics. Potentially harmful contaminants (like C. botulinum or grayanotoxins) can be found in some types of honey and should be used cautiously in pregnant or breastfeeding women.

• Hydrotherapy: Hydrotherapy is broadly defined as the external application of water in any form or temperature (hot, cold, steam, liquid, ice) for healing purposes. It may include immersion in a bath or body of water (such as the ocean or a pool), use of water jets, douches, application of wet towels to the skin, or water birth. These approaches have been used for the relief of various diseases and injuries, or for general well being. Hydrotherapy has been used in patients with pressure ulcers, and preliminary research suggests that daily whirlpool baths may reduce the time for wound healing. Better research is necessary in this area before a firm conclusion can be drawn.

• There is a risk of infection from contaminated water if sanitary conditions are not maintained. Avoid sudden or prolonged exposure to extreme temperatures in baths, wraps, saunas, or other forms of hydrotherapy, particularly with heart disease, lung disease, or if pregnant. Avoid with implanted medical devices like pacemakers, defibrillators, or hepatic (liver) infusion pumps. Vigorous use of water jets should be avoided with fractures, known blood clots, bleeding disorders, severe osteoporosis, open wounds, or during pregnancy. Use cautiously with Raynaud's disease, chilblains, acrocyanosis, erythrocyanosis, and impaired temperature sensitivity, such as neuropathy. Use cautiously if pregnant or breastfeeding. Hydrotherapy should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses. Patients with known illnesses should consult their physician(s) before starting hydrotherapy.

• Iodine: It is not clear if healing of wounds or skin ulcers is improved with the application of topical iodine solutions. Iodine solutions may assist with sterilization as a part of a larger approach to the wound healing process.

• Reactions can be severe, and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

• Magnet therapy: The use of magnets to treat illness has been described historically in many civilizations. In modern times, magnetic fields play an important role in Western medicine, including use for magnetic resonance imaging (MRI), pulsed electromagnetic fields, and experimental magnetic stimulatory techniques. Early scientific evidence suggests that the time to heal wounds, including ulcers, may decrease with the use of static magnets. Better quality studies are needed before a firm recommendation can be made for wound healing.

• Avoid with implantable medical devices, such as heart pacemakers, defibrillators, insulin pumps, or hepatic artery infusion pumps. Avoid with myasthenia gravis or bleeding disorders. Avoid if pregnant or breastfeeding. Magnet therapy is not advised as the sole treatment for potentially serious medical conditions, and it should not delay the time to diagnosis or treatment with more proven methods. Patients are advised to discuss magnet therapy with a qualified healthcare provider before starting treatment.

• Pantothenic acid (vitamin B5): Pantothenic acid (vitamin B5) is essential to all life and is a component of Coenzyme A (CoA), a molecule that is necessary for numerous vital chemical reactions to occur in cells. Pantothenic acid is essential to the metabolism of carbohydrates, proteins, and fats, as well as for the synthesis of hormones and cholesterol. In animal research, oral and topical pantothenic acid has been associated with accelerated skin wound healing. However early human study results conflict. Additional evidence is necessary before a clear conclusion can be reached regarding this use of pantothenic acid or dexpanthenol.

• Avoid if allergic or hypersensitive to pantothenic acid or dexpanthenol. Avoid with gastrointestinal blockage. Pantothenic acid is generally considered safe in pregnant and breastfeeding women when taken at recommended doses.

• Papain: Papain is an enzyme that breaks protein bonds and has been used in Africa for treating burns. In standard western medical care, papain-containing debridement agents are commonly used to remove necrotic tissue and slough in burns, postoperative wounds, pilonidal cyst wounds, carbuncles, trauma wounds, infected wounds, and chronic lesions, such as pressure ulcers, and varicose and diabetic ulcers. According to reviews and clinical trials, papain may be very useful for wound debridement and for stimulating wound healing. More high-quality research is needed in this area.

• Use cautiously in patients sensitive to papain. Use cautiously in patients being treated for prostatitis. Use Wobenzym®, which contains papain, cautiously, especially in those with bleeding disorders or taking anticoagulants or antiplatelets. Use cautiously as an adjuvant to radiation therapy. Avoid in patients with gastroesophageal reflux disease. Avoid in patients using immunosuppressive therapy.

• Physical therapy: Physical therapy techniques, such as laser treatment, have been used to clean and heal wounds. Early evidence also suggests that high voltage stimulation or pulsed electrical stimulation may speed the healing of some types of skin ulcers. More research with similar outcome measures is needed to better understand the role of physical therapy for wound care.

• Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy and although reports of major adverse effects are lacking in the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

• Psyllium: Psyllium, also referred to as ispaghula, is derived from the husks of the seeds of Plantago ovata. Psyllium contains a high level of soluble dietary fiber, and is the chief ingredient in many commonly used bulk laxatives. Results from human study suggest that psyllium may reduce the number of surgeries necessary to heal anal fissures. Further evidence is necessary.

• Avoid if allergic or hypersensitive to psyllium, ispaghula, or English plantains (Plantago lanceolata). Avoid in patients with esophageal disorders, gastrointestinal atony, fecal impaction, gastrointestinal tract narrowing, swallowing difficulties, and previous bowel surgery. Avoid ingestion of psyllium-containing products in individuals with repeated or prolonged psyllium exposure who have not manifested allergic or hypersensitive symptoms. Prescription drugs should be taken one hour before or two hours after psyllium. Adequate fluid intake is required when taking psyllium-containing products. Use cautiously with blood thinners, antidiabetic agents, carbamazepine, lithium, potassium-sparing diuretics, salicylates, tetracyclines, nitrofurantoin, calcium, iron, vitamin B12, other laxatives, tricyclic antidepressants (amitriptyline, doxepin, and imipramine), antigout agents, anti-inflammatory agents, hydrophilic agents, and chitosan. Use cautiously with diabetes and kidney dysfunction. Use cautiously if pregnant or breastfeeding.

• Rose hip: Rose hips are the fruits that develop from the blossoms of the wild rose (Rosa spp.). They are typically orange to red in color, but some species may be purple or black. When applied topically, the volatile oils of aromatic plants may have physiological effects that will facilitate wound healing. Rose hips contain several vitamins and minerals, including vitamin C, vitamin B1, vitamin E, calcium, zinc, and carotenoids, which could potentially promote wound healing when applied to the skin. Much larger and high quality clinical trials are needed to establish the therapeutic efficacy of rose hip and rose oil preparations in the topical treatment of surgical wounds and ulcers.

• Use cautiously in patients who are avoiding immune system stimulants. Use cautiously in patients who are taking anticoagulant or anti-platelet aggregating agents, antibiotics, antineoplastics, antiretrovirals, anti-inflammatory agents, "Long-Life CiLi", antilipemics, aluminum-containing antacids, salicylates, or laxatives. Avoid in patients who are allergic to rose hips, rose pollen, its constituents, or members of the Rosaceae family.

• TENS: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive technique in which a low-voltage electrical current is delivered through wires from a small power unit to electrodes located on the skin. Electrodes are temporarily attached with paste in various patterns, depending on the specific condition and treatment goals. TENS is often used to treat pain, as an alternative or addition to pain medications. Therapy sessions may last from minutes to hours. TENS is often used in conjunction with acupuncture therapy. TENS has been tested for its effects on blood flow to skin flaps used in plastic surgery procedures such as breast reconstruction. TENS has also been evaluated in patients with skin ulcers, diabetic foot ulcers, and chronic ulcers of various causes. More research is needed in this area.

• Avoid with implantable devices, like defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation, like neuropathy, and with seizure disorders. Avoid if pregnant or breastfeeding.

• Therapeutic touch: Although some studies report an improvement in wound healing with therapeutic touch, others show no benefits.

• Therapeutic touch is believed to be safe for most people. Therapeutic touch should not be used for potentially serious conditions in place of more proven therapies. Avoid with fever or inflammation, and on body areas with cancer.

• Vitamin A: In preliminary study, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound healing effects. Further research is needed to confirm these results.

• Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears to be safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Excessive doses of vitamin A have been associated with central nervous system malformations. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

• Zinc: Although zinc is frequently cited as having beneficial effects on healing of incision wounds, few studies have investigated this use. Further research is needed. There are conflicting findings regarding the potential benefit of zinc for healing leg ulcers. Available studies reported no or few adverse effects.

• Preliminary evidence suggests that topical zinc oxide oil may help manage perianal and buttock skin damage in incontinent patients. Further research is needed to better understand the role of zinc for treatment of skin damage caused by incontinence.

• Zinc is generally considered to be safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

• Fair negative scientific evidence:

• Aloe: A well-designed human trial found no benefit of topical acemannan hydrogel (a component of aloe gel) in the treatment of pressure ulcers.

• Avoid if allergic to aloe or other plants of the Liliaceae family (garlic, onions, tulips). Avoid injecting aloe. Do not apply to open skin, surgical wounds or pressure ulcers. Avoid taking by mouth with diarrhea, bowel blockage, intestinal diseases, bloody stools or hepatitis. Avoid with a history of irregular heartbeat (arrhythmia), electrolyte imbalances, diabetes, heart disease or kidney disease. Avoid taking by mouth if pregnant or breastfeeding.

Prevention

• In order to prevent wounds from occurring, healthcare providers recommend that individuals: take care when using sharp objects such as knives, scissors, saws, and trimmers; wear shoes or boots on the feet; use helmets when riding a bicycle; use helmets, kneepads, wrist protectors, and elbow pads when using in-line skates or skateboards; and avoid picking up broken pieces of glass and handling razor blades.

• If bedridden or immobile with diabetes, circulation problems, incontinence, or mental disabilities, healthcare providers recommend that the individual be checked for pressure sores every day. Also, look for reddened areas that, when pressed, do not turn white. Also look for blisters, sores, or craters. In addition, take the following steps: change position at least every two hours to relieve pressure; use items that can help reduce pressure such as pillows, sheepskin, foam padding, and powders from medical supply stores; eat healthy, well-balanced meals; exercise daily, including range-of-motion exercises for immobile patients; and keep skin clean and dry. Incontinent people need to take extra steps to limit moisture.

• Individuals with diabetes should check their feet daily for blisters, sores, or other wounds in order to prevent serious infection and possibly amputation.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. American Academy of Family Physicians. http://familydoctor.org.

2. American Academy of Pediatrics. www.aap.org.

3. Arnold M, Barbul A. Nutrition and wound healing. Plast Reconstr Surg. 2006;117(7 Suppl):42S-58S. View Abstract

4. Centers for Disease Control and Prevention. www.cdc.gov.

5. Dini V, Bertone M, Romanelli M. Prevention and management of pressure ulcers. Dermatol Ther. 2006;19(6):356-64. View Abstract

6. Langemo D, Anderson J, Hanson D, et al. Nutritional considerations in wound care. Adv Skin Wound Care. 2006;19(6):297-8, 300, 303. View Abstract

7. de Laat EH, Schoonhoven L, Pickkers P, et al. Epidemiology, risk and prevention of pressure ulcers in critically ill patients: a literature review. J Wound Care. 2006;15(6):269-75. View Abstract

8. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

9. National Institute of Allergy and Infectious Diseases. www3.niaid.nih.gov.

10. Pieper B, Sieggreen M, Nordstrom CK, et al. Discharge knowledge and concerns of patients going home with a wound. J Wound Ostomy Continence Nurs. 2007;34(3):245-53; quiz 254-5. View Abstract

11. Wu SC, Driver VR, Wrobel JS, et al. Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manag. 2007;3(1):65-76. View Abstract