Breast Cancer

Breast cancer (malignant breast neoplasm) is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk.  Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas.

The size, stage, rate of growth, and other characteristics of the tumor determine the kinds of treatment. Treatment may include surgery, drugs (hormonal therapy and chemotherapy), radiation and/or immunotherapy.  Surgical removal of the tumor provides the single largest benefit, with surgery alone being capable of producing a cure in many cases. To somewhat increase the likelihood of long-term disease-free survival, several chemotherapy regimens are commonly given in addition to surgery. Most forms of chemotherapy kill cells that are dividing rapidly anywhere in the body, and as a result cause temporary hair loss and digestive disturbances. Radiation may be added to kill any cancer cells in the breast that were missed by the surgery, which usually extends survival somewhat, although radiation exposure to the heart may cause heart failure in the future.  Some breast cancers are sensitive to hormones such as estrogen and/or progesterone, which makes it possible to treat them by blocking the effects of these hormones.

Prognosis and survival rate varies greatly depending on cancer type and staging. With best treatment and dependent on staging, 5-year relative survival varies from 98% to 23, with an overall survival rate of 85%.

Worldwide, breast cancer comprises 22.9% of all non-melanoma skin cancers in women.In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women). Breast cancer is more than 100 times more common in women than breast cancer in men, although males tend to have poorer outcomes due to delays in diagnosis.[

Classification

Breast cancers can be classified by different schemata. Every aspect influences treatment response and prognosis. Description of a breast cancer would optimally include multiple classification aspects, as well as other findings, such as signs found on physical exam. Classification aspects include stage (TNM), pathology, grade, receptor status, and the presence or absence of genes as determined by DNA testing:

Stage. The TNM classification for breast cancer is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.

The main stages are:

Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).

Stages 1–3 are defined as 'early' cancer with a good prognosis.

Stage 4 is defined as 'advanced' and/or 'metastatic' cancer with a poor prognosis.

Histopathology. Breast cancer is usually classified primarily by its histological appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as ductal or lobular carcinoma. Carcinoma in situ is growth of low grade cancerous or precancerous cells in particular tissue compartment such as the mammary duct without invasion of the surrounding tissue. In contrast, invasive carcinoma does not confine itself to the initial tissue compartment and invades the surrounding tissue.

Grade (Bloom-Richardson grade). When cells become differentiated, they take different shapes and forms to function as part of an organ. Cancerous cells lose that differentiation. In cancer grading, tumor cells are generally classified as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Poorly differentiated cancers have a worse prognosis.

Receptor status. Cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to these receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu.

ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), and generally have a better prognosis.

HER2+ breast cancer had a worse prognosis,  but HER2+ cancer cells respond to drugs such as the monoclonal antibody, trastuzumab, (in combination with conventional chemotherapy) and this has improved the prognosis significantly.  Cells with none of these receptors are called basal-like or triple negative.

DNA assays of various types including DNA microarrays have compared normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways, and may assist in choosing the most effective treatment for that DNA type.

Signs and symptoms

Breast cancer showing an inverted nipple, lump, skin dimpling

The first noticeable symptom of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump. The earliest breast cancers are detected by a mammogram. Lumps found in lymph nodes located in the armpits  can also indicate breast cancer.

Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.

Inflammatory breast cancer is a special type of breast cancer which can pose a substantial diagnostic challenge. Symptoms may resemble a breast inflammation and may include pain, swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.

In rare cases, what initially appears as a fibroadenoma (hard movable lump) could in fact be a phyllodes tumor. Phyllodes tumors are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline, or malignant.

Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific", meaning they can also be manifestations of many other illnesses.

Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.

Risk factors

The primary risk factors for breast cancer are sex,  age,lack of childbearing or breastfeeding, higher hormone levels,  race, economic status and dietary iodine deficiency.

Most cases of breast cancer cannot be prevented through any action on the part of the affected person. The World Cancer Research Fund estimated that 38% of breast cancer cases in the US are preventable through reducing alcohol intake, increasing physical activity levels and maintaining a healthy weight.  It also estimated that 42% of breast cancer cases in the UK could be prevented in this way, as well as 28% in Brazil and 20% in China.

Smoking tobacco also increases the risk of breast cancer with the greater the amount smoking and the earlier in life smoking begins the higher the risk.

In a study of attributable risk and epidemiological factors published in 1995, later age at first birth and not having children accounted for 29.5% of U.S. breast cancer cases, family history of breast cancer accounted for 9.1% and factors correlated with higher income contributed 18.9% of cases. Attempts to explain the increased incidence (but lower mortality) correlated with higher income include epidemiologic observations such as lower birth rates correlated with higher income and better education, possible overdiagnosis and overtreatment because of better access to breast cancer screening, and the postulation of as yet unexplained lifestyle and dietary factors correlated with higher income. One such factor may be past hormone replacement therapy, which was typically more widespread in higher income groups.

The genes associated with hereditary breast-ovarian cancer syndromes usually increase the risk slightly or moderately; the exception is women and men who are carriers of BRCA mutations. These people have a very high lifetime risk for breast and ovarian cancer, depending on the portion of the proteins where the mutation occurs. Instead of a 12 percent lifetime risk of breast cancer, women with one of these genes have a risk of approximately 60 percent.

In more recent years, research has indicated the impact of diet and other behaviors on breast cancer. These additional risk factors include a high-fat diet, alcohol intake, obesity, and environmental factors such as tobacco use, radiation, endocrine disruptors and shiftwork. Although the radiation from mammography is a low dose, the cumulative effect can cause cancer.

In addition to the risk factors specified above, demographic and medical risk factors include:

Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting a second breast cancer.

Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer, the risk becomes significant if at least two close relatives had breast or ovarian cancer. The risk is higher if her family member got breast cancer before age 40. An Australian study found that having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk of breast cancer and other forms of cancer, including brain and lung cancers.

Certain breast changes: Atypical hyperplasia and lobular carcinoma in situ found in benign breast conditions such as fibrocystic breast changes are correlated with an increased breast cancer risk.

Those with a normal body mass index at age 20 who gained weight as they aged had nearly double the risk of developing breast cancer after menopause in comparison to women who maintained their weight. The average 60-year-old woman's risk of developing breast cancer by age 65 is about 2 percent; her lifetime risk is 13 percent.

Prevention

Exercise may decrease breast cancer risk. Also avoiding alcohol and obesity. Prophylactic bilateral mastectomy may be considered in patients with BRCA1 and BRCA2 mutations.A 2007 report concluded that women can somewhat reduce their risk by maintaining a healthy weight, drinking less alcohol, being physically active and breastfeeding their children.

Mastitis

Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well

Terminology

Popular usage of the term mastitis varies by geographic region. Outside the US it is commonly used for puerperal and nonpuerperal cases, in the US the term nonpuerperal mastitis is rarely used and alternative names such as duct ectasia, subareolar abscess and plasma cell mastitis are more frequently used.

Chronic cystic mastitis is a different (older) name for fibrocystic disease.

American usage: mastitis usually refers to puerperal (occurring to breastfeeding mothers) mastitis with symptoms of systemic infection. Lighter cases of puerperal mastitis are often called breast  engorgement.

In this article mastitis is used in the original sense of the definition as inflammation of the breast with additional qualifiers where appropriate.

Types

It is called puerperal mastitis when it occurs in lactating mothers and non-puerperal otherwise. Mastitis can occur in men, albeit rarely. Inflammatory breast cancer has symptoms very similar to mastitis and must be ruled out.

The popular misconception that mastitis in humans is an infection is highly misleading and in many cases incorrect. Infections play only a minor role in the pathogenesis of both puerperal and nonpuerperal mastitis in humans and many cases of mastitis are completely aseptic under normal hygienic conditions. Infection as primary cause of mastitis is presumed to be more prevalent in veterinary mastitis and poor hygienic conditions.

The symptoms are similar for puerperal and nonpuerperal mastitis but predisposing factors and treatment can be very different.

Puerperal

Puerperal mastitis is the inflammation of breast in connection with pregnancy, breastfeeding or weaning. Since one of the most prominent symptoms is tension and engourgement of the breast, it is thought to be caused by blocked milk ducts or milk excess. It is relatively common, estimates range depending on methodology between 5-33%. However only about 0.4-0.5% of breastfeeding mothers develop an abscess.

Nonpuerperal

The term nonpuerperal mastitis describes inflammatory lesions of the breast occurring unrelated to pregnancy and breastfeeding. This article includes description of mastitis as well as various kinds of mammary abscesses. Skin related conditions like dermatitis and foliculitis are a separate entity.

Names for non-puerperal mastitis are not used very consistently and include Mastitis, Subareolar Abscess, Duct Ectasia, Periductal Inflammation, Zuska's Disease and others.

Symptoms

Lactation mastitis usually affects only one breast and the symptoms can develop quickly. The signs and symptoms usually appear suddenly and they include:

Breast tenderness or warmth to the touch

General malaise or feeling ill

Swelling of the breast

Pain or a burning sensation continuously or while breast-feeding

Skin redness, often in a wedge-shaped pattern

Fever of 101 F (38.3 C) or greater

The affected breast can then start to appear lumpy and red.

Some women may also experience flu-like symptoms such as:

Aches

Shivering and chills

Feeling anxious or stressed

Fatigue

Breast engorgement

Contact should be made with a health care provider with special breastfeeding competence as soon as the patient recognizes the combination of signs and symptoms. Most of the women first experience the flu-like symptoms and just after they may notice a sore red area on the breast. Also, women should seek medical care if they notice any abnormal discharge from the nipples, if breast pain is making it difficult to function each day or they have prolonged, unexplained breast pain.

Causes

Since the 1980s mastitis has often been divided into non-infectious and infectious sub-groups. However, recent research  suggests that it may not be feasible to make divisions in this way. It has been shown that types and amounts of potentially pathogenic bacteria in breast milk are not correlated to the severity of symptoms. Moreover, although only 15% of women with mastitis in Kvist et al.'s study were given antibiotics, all recovered and few had recurring symptoms. Many healthy breastfeeding women wishing to donate breast milk have potentially pathogenic bacteria in their milk but have no symptoms of mastitis.

Mastitis typically develops when the milk is not properly removed from the breast. Milk stasis can lead to the milk ducts in the breasts becoming blocked, as the breast milk not being properly and regularly expressed. It has also been suggested that blocked milk ducts can occur as a result of pressure on the breast, such as tight-fitting clothing or an over-restrictive bra, although there is sparse evidence for this supposition . Mastitis may occur when the baby is not appropriately attached to the breast while feeding, when the baby has infrequent feeds or has problems suckling the milk out of the breast.

Experts are still unsure why breast milk can cause the breast tissue to become inflamed. One theory is that it may be due to the presence of cytokines in breast milk. Cytokines are special proteins that are used by the immune system and are passed on to the baby in order to help them resist infection. It may be the case that the woman's immune system mistakes these cytokines for a bacterial or viral infection and responds by inflaming the breast tissue in an attempt to stop the spread of what the body perceives as an infection.

Some women (approximately 15% in Kvist et al. study) will require antibiotic treatment for infection which is usually caused by bacteria from the skin or the baby's mouth that entering the milk ducts through skin lesions of the nipple or through the opening of the nipple. Infection is usually caused by staphylococcus aureus.

Mastitis is quite common among breastfeeding women. The WHO estimates that although incidences vary between 2.6% and 33%, the prevalence globally is approximately 10% of breastfeeding women. Most mothers who develop mastitis usually do so within the first few weeks after delivery. Most breast infections occur within the first or second month after delivery or at the time of weaning. However, in rare cases it affects women who are not breastfeeding.

Mastitis can also develop after nipple piercing. In some rare cases, however, Mastitis can occur in men.

Risk Factors

Women who are breastfeeding are at risk for developing mastitis especially if they have sore or cracked nipples or have had mastitis before while breastfeeding another baby. Also, the chances of getting mastitis increases if women use only one position to breastfeed or wear a tight-fitting bra, which may restrict milk flow

Women with diabetes, chronic illness, AIDS, or an impaired immune system may be more susceptible to the development of mastitis.

Complications

Complications that may arise from mastitis include recurrence, milk stasis and abscess. The abscess is the most severe complication that women can get from this condition. Also, women who have had mastitis once are likely to develop it again with a future child or with the same infant. Recurrence appears especially in cases of delayed or inadequate treatment.

Milk stasis is another complication that may arise from mastitis and it occurs when the milk is not completely drained from the breast. This causes increased pressure on the ducts and leakage of milk into surrounding breast tissue, which can lead to pain and inflammation.

Delayed treatment or inadequate treatment, especially in mastitis related to milk stasis, may lead to the formation of an abscess within the breast tissue. An abscess is a collection of pus that develops into the breast which ultimately requires surgical drainage.

Tests and diagnosis

The diagnosis of mastitis and breast abscess can usually be made based on a physical examination.The doctor will also take into account the signs and symptoms of the condition.

However, if the doctor is not sure whether the mass is an abscess or a tumor, an ultrasound may be performed. The ultrasound provides a clear image of the breast tissue and may be helpful in distinguishing between simple mastitis and abscess or in diagnosing an abscess deep in the breast. The test consists of placing an ultrasound probe over the breast.

In cases of infectious mastitis, cultures may be needed in order to determine what type of organism is causing the infection. Cultures are helpful in deciding the specific type of antibiotics that will be used in curing the disease. These cultures may be taken either from the breast milk or of the material aspirated from an abscess.

Mammograms or breast biopsies are normally performed on women who do not respond to treatment or on non-breastfeeding women. This type of tests is sometimes ordered to exclude the possibility of a rare type of breast cancer which causes symptoms similar to those of mastitis.

Breast cancer

Breast cancer may coincide with or mimic symptoms of mastitis. Only full resolution of symptoms and careful examination are sufficient to exclude the diagnosis of breast cancer.

Lifetime risk for breast cancer is significantly reduced for women who were pregnant and breastfeeding. Mastitis episodes do not appear to influence lifetime risk of breast cancer.

Mastitis does however cause great difficulties in diagnosis of breast cancer and delayed diagnosis and treatment can result in worse outcome.

Breast cancer may coincide with mastitis or develop shortly afterwards. All suspicious symptoms that do not completely disappear within 5 weeks must be investigated.

Breast cancer incidence during pregnancy and lactation is assumed to be the same as in controls. Course and prognosis are also very similar to age matched controls.However diagnosis during lactation is particularly problematic, often leading to delayed diagnosis and treatment.

Some data suggests that noninflammatory breast cancer incidence is increased within a year following episodes of nonpuerperal mastitis and special care is required for followup cancer prevention screening. So far only data from short term observation is available and total risk increase can not be judged. Because of the very short time between presentation of mastitis and breast cancer in this study it is considered very unlikely that the inflammation had any substantial role in carcinogenesis, rather it would appear that some precancerous lesions may increase the risk of inflammation (hyperplasia causing duct obstruction, hypersensitivity to cytokines or hormones) or the lesions may have common predisposing factors.

A very serious type of breast cancer called inflammatory breast cancer presents with similar symptoms as mastitis (both puerperal and nonpuerperal). It is the most aggressive type of breast cancer with the highest mortality rate. The inflammatory phenotype of IBC is thought to be mostly caused by invasion and blocking of dermal lymphatics, however it was recently shown that NF-κB target genes activation may significantly contribute to the inflammatory phenotype. Case reports show that inflammatory breast cancer symptoms can flare up following injury or inflammation making it even more likely to be mistaken for mastitis. Symptoms are also known to partially respond to progesterone and antibiotics, reaction to other common medications can not be ruled out at this point

Turmeric (Curcuma longa)

Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae. It is native to tropical South Asia and needs temperatures between 20 °C and 30 °C and a considerable amount of annual rainfall to thrive. Plants are gathered annually for their rhizomes, and propagated from some of those rhizomes in the following season.

When not used fresh, the rhizomes are boiled for several hours and then dried in hot ovens, after which they are ground into a deep orange-yellow powder commonly used as a spice in curries and other South Asian and Middle Eastern cuisine, for dyeing, and to impart color to mustard condiments. Its active ingredient is curcumin and it has a distinctly earthy, slightly bitter, slightly hot peppery flavor and a mustardy smell.

In medieval Europe, turmeric became known as Indian saffron, since it was widely used as an alternative to the far more expensive saffron spice.

Erode, a city in the south Indian state of Tamil Nadu, is the world's largest producer and most important trading center of turmeric in Asia. For these reasons, Erode in history is also known as "Yellow City" or "Turmeric City". Sangli, a town in the southern part of the Indian western state of Maharashtra, is the second largest and most important trading center for turmeric in Asia. Turmeric is commonly called haridra or haldi in India.

Composition

Turmeric contains up to 5% essential oils and up to 5% curcumin, a polyphenol. Curcumin is the active substance of turmeric and curcumin is known as C.I. 75300, or Natural Yellow 3. The systematic chemical name is (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione.

It can exist at least in two tautomeric forms, keto and enol. The keto form is preferred in solid phase and the enol form in solution. Curcumin is a pH indicator. In acidic solutions (pH <7.4) it turns yellow, whereas in basic (pH > 8.6) solutions it turns bright red.

Usage

Culinary uses

Turmeric grows wild in the forests of South and Southeast Asia. It has become the key ingredient for many Indian, Persian and Thai dishes such as in curry and many more.

In Indonesia, the turmeric leaves are used for Minangese or Padangese curry base of Sumatra, such as rendang, sate padang and many other varieties.

Although most usage of turmeric is in the form of root powder, in some regions (especially in Maharashtra), leaves of turmeric are used to wrap and cook food. This usually takes place in areas where turmeric is grown locally, since the leaves used are freshly picked. This imparts a distinct flavor.

In recipes outside South Asia, turmeric is sometimes used as an agent to impart a rich, custard-like yellow color. It is used in canned beverages and baked products, dairy products, ice cream, yogurt, yellow cakes, orange juice, biscuits, popcorn color, sweets, cake icings, cereals, sauces, gelatins, etc.[citation needed] It is a significant ingredient in most commercial curry powders. Turmeric is mostly used in savory dishes, as well as some sweet dishes, such as the cake sfouf.

Although usually used in its dried, powdered form, turmeric is also used fresh, much like ginger. It has numerous uses in Far Eastern recipes, such as fresh turmeric pickle, which contains large chunks of soft turmeric.

Turmeric (coded as E100 when used as a food additive) is used to protect food products from sunlight. The oleoresin is used for oil-containing products. The curcumin/polysorbate solution or curcumin powder dissolved in alcohol is used for water-containing products. Over-coloring, such as in pickles, relishes, and mustard, is sometimes used to compensate for fading.

In combination with annatto (E160b), turmeric has been used to color cheeses, yogurt, dry mixes, salad dressings, winter butter and margarine. Turmeric is also used to give a yellow color to some prepared mustards, canned chicken broths and other foods (often as a much cheaper replacement for saffron).

Turmeric is widely used as a spice in South Asian and Middle Eastern cooking. Many Persian dishes use turmeric as a starter ingredient for almost all Iranian fry ups (which typically consist of oil, onions and turmeric followed by any other ingredients that are to be included). In Nepal, turmeric is widely grown and is extensively used in almost every vegetable and meat dish in the country for its color, as well as for its medicinal value. In South Africa, turmeric is traditionally used to give boiled white rice a golden color.

In Goa and Dakshina Kannada (Karnataka state, India), turmeric plant leaf is used to prepare special sweet dishes, patoleo, by layering on the leaf — rice flour, and coconut-jaggery mixture, and then closing and steaming in a special copper steamer (goa).

Preliminary medical research

Turmeric is currently being investigated for possible benefits in Alzheimer's disease, cancer, arthritis, and other clinical disorders. As an example of preliminary laboratory research, turmeric ameliorated the severity of pancreatitis-associated lung injury in mice.

In the latter half of the 20th century, curcumin was identified as responsible for most of the biological effects of turmeric. According to a 2005 article in the Wall Street Journal, research activity into curcumin and turmeric is increasing. The U.S. National Institutes of Health currently has registered 61 clinical trials completed or underway to study use of dietary curcumin for a variety of clinical disorders (dated June 2011).

Uses in folk medicine

In Ayurvedic practices, turmeric has been used as an anti-inflammatory agent and remedy for gastrointestinal discomfort associated with irritable bowel syndrome and other digestive disorders. Raw turmeric strengthens cartilage and bone structure. It is traditionally taken in warm milk at night before sleep. Some may use turmeric in skin creams as an antiseptic agent for cuts, burns and bruises. It is popular as a tea in Okinawa, Japan.

Cosmetics

Turmeric paste is traditionally used by Indian women to keep them free of superfluous hair and as an antimicrobial. Turmeric paste, as part of both home remedies and Ayurveda, is also said to improve the skin and is touted as an anti-aging agent. Turmeric figures prominently in the bridal beautification ceremonies of India, Bangladesh, and Pakistan. Staining oneself with turmeric is believed to improve the skin tone and tan. Turmeric is currently used in the formulation of some sunscreens.

The government of Thailand is funding a project to extract and isolate tetrahydrocurcuminoids (THC) from turmeric. THCs are colorless compounds that might have antioxidant and skin-lightening properties, and might be used to treat skin inflammations, making these compounds useful in cosmetics formulations.

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Sinusitis

Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days. It is a common condition; for example, in the United States more than 24 million cases occur annually.

Classification

By duration

Sinusitis can be acute (going on less than four weeks), subacute (4–8 weeks) or chronic (going on for 8 weeks or more). All three types of sinusitis have similar symptoms, and are thus often difficult to distinguish. Acute sinusitis is very common. Roughly ninety percent of adults have had sinusitis at some point in their life.

Acute

Acute sinusitis is usually precipitated by an earlier upper respiratory tract infection, generally of viral origin. If the infection is of bacterial origin, the most common three causative agents are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.[4] Until recently, Haemophilus influenzae was the most common bacterial agent to cause sinus infections. However, introduction of the H. influenza type B (Hib) vaccine has dramatically decreased H. influenza type B infections and now non-typable H. influenza (NTHI) are predominantly seen in clinics. Other sinusitis-causing bacterial pathogens include Staphylococcus aureus and other streptococci species, anaerobic bacteria and, less commonly, gram negative bacteria. Viral sinusitis typically lasts for 7 to 10 days,[4] whereas bacterial sinusitis is more persistent. Approximately 0.5% to 2% of viral sinusitis results in subsequent bacterial sinusitis. It is thought that nasal irritation from nose blowing leads to the secondary bacterial infection.

Acute episodes of sinusitis can also result from fungal invasion. These infections are typically seen in patients with diabetes or other immune deficiencies (such as AIDS or transplant patients on immunosuppressive anti-rejection medications) and can be life threatening. With type I diabetes, ketoacidosis causes sinusitis by Mucormycosis.

Chemical irritation can also trigger sinusitis, commonly from cigarette smoke and chlorine fumes. Rarely, it may be caused by a tooth infection.

Chronic

Chronic sinusitis, by definition, lasts longer than three months and can be caused by many different diseases that share chronic inflammation of the sinuses as a common symptom. Symptoms of chronic sinusitis may include any combination of the following: nasal congestion, facial pain, headache, night-time coughing, an increase in previously minor or controlled asthma symptoms, general malaise, thick green or yellow discharge, feeling of facial 'fullness' or 'tightness' that may worsen when bending over, dizziness, aching teeth, and/or halitosis.[citation needed] Each of these symptoms has multiple other possible causes, which should be considered and investigated as well. Unless complications occur, fever is not a feature of chronic sinusitis.Often chronic sinusitis can lead to anosmia, a reduced sense of smell. In a small number of cases, acute or chronic maxillary sinusitis is associated with a dental infection. Vertigo, lightheadedness, and blurred vision are not typical in chronic sinusitis and other causes should be investigated.

Chronic sinusitis cases are subdivided into cases with polyps and cases without polyps. When polyps are present, the condition is called chronic hyperplastic sinusitis; however, the causes are poorly understood and may include allergy, environmental factors such as dust or pollution, bacterial infection, or fungus (either allergic, infective, or reactive). Non-allergic factors, such as vasomotor rhinitis, can also cause chronic sinus problems. Abnormally narrow sinus passages, such as having a deviated septum, can impede drainage from the sinus cavities and be a contributing factor. A combination of anaerobic and aerobic bacteria, are detected in conjunction with chronic sinusitis, Staphylococcus aureus (including methicilin resistant S.aureus )and coagulase-negative Staphylococci. Typically antibiotic treatment provides only a temporary reduction in inflammation, although hyperresponsiveness of the immune system to bacteria has been proposed as a possible cause of sinusitis with polyps (chronic hyperplastic sinusitis).

Attempts have been made to provide a more consistent nomenclature for subtypes of chronic sinusitis. The presence of eosinophils in the mucous lining of the nose and paranasal sinuses has been demonstrated for many patients, and this has been termed Eosinophilic Mucin RhinoSinusitis (EMRS).[citation needed] Cases of EMRS may be related to an allergic response, but allergy is not often documented, resulting in further subcategorization into allergic and non-allergic EMRS.

A more recent, and still debated, development in chronic sinusitis is the role that fungus plays in this disease. Fungus can be found in the nasal cavities and sinuses of most patients with sinusitis, but can also be found in healthy people as well.[citation needed] It remains unclear if fungus is a definite factor in the development of chronic sinusitis and if it is, what the difference may be between those who develop the disease and those who remain symptom free. Trials of antifungal treatments have had mixed results.

By location

There are several paired paranasal sinuses, including the frontal, ethmoid, maxillary and sphenoid sinuses. The ethmoid sinuses is further subdivided into anterior and posterior ethmoid sinuses, the division of which is defined as the basal lamella of the middle turbinate. In addition to the severity of disease, discussed below, sinusitis can be classified by the sinus cavity which it affects:

Maxillary – can cause pain or pressure in the maxillary (cheek) area (e.g., toothache, headache) .

Frontal – can cause pain or pressure in the frontal sinus cavity (located above eyes), headache .

Ethmoid – can cause pain or pressure pain between/behind the eyes and headaches .

Sphenoid – can cause pain or pressure behind the eyes, but often refers to the vertex, or top of the head

Recent theories of sinusitis indicate that it often occurs as part of a spectrum of diseases that affect the respiratory tract (i.e., the "one airway" theory) and is often linked to asthma.  All forms of sinusitis may either result in, or be a part of, a generalized inflammation of the airway, so other airway symptoms, such as cough, may be associated with it.

Signs and symptoms

Headache/facial pain or pressure of a dull, constant, or aching sort over the affected sinuses is common with both acute and chronic stages of sinusitis. This pain is typically localized to the involved sinus and may worsen when the affected person bends over or when lying down. Pain often starts on one side of the head and progresses to both sides.  Acute and chronic sinusitis may be accompanied by thick nasal discharge that is usually green in colour and may contain pus (purulent) and/or blood. Often a localized headache or toothache is present, and it is these symptoms that distinguish a sinus-related headache from other types of headaches, such as tension and migraine headaches. Infection of the eye socket is possible, which may result in the loss of sight and is accompanied by fever and severe illness. Another possible complication is the infection of the bones (osteomyelitis) of the forehead and other facial bones – Pott's puffy tumor.

Sinus infections can also cause inner ear problems due to the congestion of the nasal passages. This can be demonstrated by dizziness, "a pressurized or heavy head", or vibrating sensations in the head.

Recent studies suggest that up to 90% of "sinus headaches" are actually migraines.  The confusion occurs in part because migraine involves activation of the trigeminal nerves, which innervate both the sinus region and the meninges surrounding the brain. As a result, it is difficult to accurately determine the site from which the pain originates. Additionally, nasal congestion can be a common result of migraine headaches, due to the autonomic nerve stimulation that can also cause in tearing (lacrimation) and a runny nose (rhinorrhea). A study found that patients with "sinus headaches" responded to triptan migraine medications, but stated dissatisfaction with their treatment when they are treated with decongestants or antibiotics.  It is important to note that migraines will not produce the thick nasal discharge that is a common symptom of a sinus infection.

Complications

The close proximity of the brain to the sinuses makes the most dangerous complication of sinusitis, particularly involving the frontal and sphenoid sinuses, infection of the brain by the invasion of anaerobic bacteria through the bones or blood vessels. Abscesses,  meningitis, and other life-threatening conditions may result. In extreme cases the patient may experience mild personality changes, headache, altered consciousness, visual problems, seizures, coma, and possibly death.

Causes

Factors which may predispose someone to developing sinusitis include: allergies; structural abnormalities, such as a deviated septum, small sinus ostia or a concha bullosa; nasal polyps; carrying the cystic fibrosis gene, though research is still tentative; and prior bouts of sinusitis, because each instance may result in increased inflammation of the nasal or sinus mucosa and potentially further narrow the nasal passageways.

Second hand smoke may also be associated with chronic rhinosinusitis.

Another cause of chronic sinusitus can be from the maxillary sinuses that are situated within the cheekbones. Infections and inflammation are more common here than in any of the other paranasal sinuses. This is because the drainage of mucous secretions from the maxillary sinus to the nasal cavity is not very efficient.

Maxillary sinusitis may also be of dental origin and constitutes a significant percentage, given the intimacy of the relationship between the teeth and the sinus floor. Complementary tests based on conventional radiology techniques and modern are needed. Their indication is based on the clinical context.

Chronic sinusitis can also be caused indirectly through a common but slight abnormality within the auditory or Eustachian tube, which is connected to the sinus cavities and the throat. This tube is usually almost level with the eye sockets but when this sometimes hereditary abnormality is present, it is below this level and sometimes level with vestibule or nasal entrance. This almost always causes some sort of blockage within the sinus cavities ending in infection and usually resulting in chronic sinusitis.

Pathophysiology

It has been hypothesized that biofilm bacterial infections may account for many cases of antibiotic-refractory chronic sinusitis.  Biofilms are complex aggregates of extracellular matrix and inter-dependent microorganisms from multiple species, many of which may be difficult or impossible to isolate using standard clinical laboratory techniques.  Bacteria found in biofilms have their antibiotic resistance increased up to 1000 times when compared to free-living bacteria of the same species. A recent study found that biofilms were present on the mucosa of 75% of patients undergoing surgery for chronic sinusitis.

Diagnosis

Acute

Bacterial and viral acute sinusitis are difficult to distinguish. However, if symptoms last less than 10 days, it is generally considered viral sinusitis. When symptoms last more than 10 days, it is considered bacterial sinusitis (usually 30% to 50% are bacterial sinusitis). Hospital acquired acute sinusitis can be confirmed by performing a CT scan of the sinuses.

Chronic

For sinusitis lasting more than eight weeks,  diagnostic criteria are lacking. A CT scan is recommended, but this alone is insufficient to confirm the diagnosis. Nasal endoscopy, a CT scan, and clinical symptoms are all used to make a positive diagnosis.  A tissue sample for histology and cultures can also be collected and tested. Allergic fungal sinusitis (AFS) is often seen in people with asthma and nasal polyps. Examining multiple biopsy samples can be helpful to confirm the diagnosis. In rare cases, sinusoscopy may be made.

Nasal endoscopy involves inserting a flexible fiber-optic tube with a light and camera at its tip into the nose to examine the nasal passages and sinuses. This is generally a completely painless (although uncomfortable) procedure which takes between five to ten minutes to complete.

Treatment

Conservative

Nasal irrigation may help with symptoms of chronic sinusitis. Decongestant nasal sprays containing oxymetazoline may provide relief, but these medications should not be used for more than the recommended period. Longer use may cause rebound sinusitis. Other recommendations include applying a warm, moist washcloth several times a day; drinking sufficient fluids in order to thin the mucus and inhaling steam two to four times a day.

Antibiotics

The vast majority of cases of sinusitis are caused by viruses and will therefore resolve without antibiotics. However, if symptoms do not resolve within 10 days, amoxicillin is a reasonable antibiotic to use first for treatment with amoxicillin/clavulanate (Augmentin) being indicated when the patient's symptoms do not improve on amoxicillin alone. The presence of aerobic and anaerobic beta-lactamase producing organisms may account for this failure. These organisms can "protect" even non beta lactamase producing bacteria from penicillins. Fluoroquinolones, and a newer macrolide antibiotic such as clarithromycin or a tetracycline like doxycycline, are used in patients who are allergic to penicillins. One study found 60 to 90% of people do not experience resolution of maxillary sinusitis using antibiotics. A short-course (3–7 days) of antibiotics seems to be effective for patients who present without severe disease or any complicating factors.

Corticosteroids

For unconfirmed acute sinusitis, intranasal corticosteroids have not been found to be better than placebo either alone or in combination with antibiotics. However for cases confirmed by radiology or nasal endoscopy treatment with corticosteroids alone or in combination with antibiotics is supported.

Surgery

For chronic or recurring sinusitis, referral to an otolaryngologist specialist may be indicated, and treatment options may include nasal surgery. Surgery should only be considered for those patients who do not experience sufficient relief from optimal medication.

A relatively recent advance in the treatment of sinusitis is a type of surgery called functional endoscopic sinus surgery (FESS). This surgery removes anatomical and pathological obstructions associated with sinusitis in order to restore normal clearance of the sinuses. This replaces prior open techniques requiring facial or oral incisions and refocuses the technique to the natural openings of the sinuses instead of promoting drainage by gravity, the idea upon which the Caldwell-Luc surgery was based.

A number of surgical approaches can be used to access the sinuses and these have generally shifted from external/extranasal approaches to intranasal endoscopic ones. The benefit of the Functional Endoscopic Sinus Surgery FESS is its ability to allow for a more targeted approach to the affected sinuses, reducing tissue disruption, and minimizing post-operative complications.

Another recently developed treatment is balloon sinuplasty. This method, similar to balloon angioplasty used to "unclog" arteries of the heart, utilizes balloons in an attempt to expand the openings of the sinuses in a less invasive manner. The utility of this treatment for sinus disease is still under debate but appears promising.

For persistent symptoms and disease in patients who have failed medical and the functional endoscopic approaches, older techniques can be used to address the inflammation of the maxillary sinus, such as the Caldwell-Luc radical antrostomy. This surgery involves an incision in the upper gum, opening in the anterior wall of the antrum, removal of the entire diseased maxillary sinus mucosa and drainage is allowed into inferior or middle meatus by creating a large window in the lateral nasal wall.)

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Kidney Stones

Kidney stones (called renal calculi (from Latin ren, renes, "kidney" and calculi, "pebbles" in medical parlance) are solid concretions or crystal aggregations formed in the kidneys from dietary minerals in the urine. Kidney stones are typically classified by their location in the kidney (nephrolithiasis), ureter (ureterolithiasis), or bladder (cystolithiasis), or by their chemical composition (calcium-containing, struvite, uric acid, or other compounds). Kidney stones are a significant source of morbidity. 80% of those with kidney stones are men. Men most commonly experience their first episode between age 30–40 years, while for women the age at first presentation is somewhat later.

Kidney stones typically leave the body by passage in the urine stream, and many stones are formed and passed without causing symptoms. If stones grow to sufficient size (usually at least 2–3 millimeters), they can cause obstruction of the ureter. Ureteral obstruction causes postrenal azotemia and hydronephrosis (distension and dilation of the renal pelvis and calyces), as well as spasm of the ureter. This leads to pain, most commonly felt in the flank, lower abdomen and groin (a condition called renal colic). Renal colic can be associated with nausea, vomiting, fever, blood in the urine, pus in the urine, and painful urination. Renal colic typically comes in waves lasting 20 to 60 minutes, beginning in the flank or lower back and often radiating to the groin or genitals. The diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, urinalysis, and radiographic studies. ultrasound examination and blood tests may also aid in the diagnosis.

When a stone causes no symptoms, watchful waiting is a valid option. For symptomatic stones, pain control is usually the first measure, using medications such as non-steroidal anti-inflammatory drugs (NSAIDs) or opioids. More severe cases may require surgical intervention. For example, some stones can be shattered into smaller fragments using extracorporeal shock wave lithotripsy (ESWL). Some cases require more invasive forms of surgery. Examples of these are cystoscopic procedures such as laser lithotripsy, or percutaneous techniques such as percutaneous nephrolithotomy. Sometimes, a tube may be placed in the ureter (a ureteral stent) to bypass the obstruction in the ureter and alleviate the symptoms.

Classification

Kidney stones are typically classified by their location or their chemical composition.

Location

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis (from Greek νεφρός (nephros, "kidney") and λίθoς (lithos, "stone")) refers to the presence of such calculi in the kidneys. Calyceal calculi refers to aggregations in either the minor or major calyx, parts of the kidney which pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus or calculi are located in the ureter. Stones may also form or pass into the bladder, a condition referred to as cystolithiasis.

Chemical composition

By far the most common type of kidney stones worldwide are those which contain calcium. For example, calcium-containing stones represent about 80% of all cases in the United States; these typically contain calcium oxalate either alone or in combination with calcium phosphate in the form of apatite or brushite. Factors that promote the precipitation of oxalate crystals in the urine, such as primary hyperoxaluria, are associated with the development of calcium oxalate stones. The formation of calcium phosphate stones is associated with conditions such as hyperparathyroidism and renal tubular acidosis.

Struvite stones

About 10–15% of urinary calculi are composed of struvite (ammonium magnesium phosphate, NH4MgPO4•6H2O). Struvite stones (also known as "infection stones", urease or triple-phosphate stones), form most often in the presence of infection by urea-splitting bacteria. Using the enzyme urease, these organisms metabolize urea into ammonia and carbon dioxide. This alkalinizes the urine, resulting in favorable conditions for the formation of struvite stones. Proteus mirabilis, Proteus vulgaris and Morganella morganii are the most common organisms isolated; less common organisms include Ureaplasma urealyticum, and some species of Providencia, Klebsiella, Serratia, and Enterobacter. These infection stones are commonly observed in people who have factors which predispose them to urinary tract infections, such as those with spinal cord injury and other forms of neurogenic bladder, ileal conduit urinary diversion, vesicoureteral reflux, and obstructive uropathies. They are also commonly seen in people with underlying metabolic disorders, such as idiopathic hypercalciuria, hyperparathyroidism, and gout. Infection stones can grow rapidly, forming large calyceal staghorn calculi requiring invasive surgery such as percutaneous nephrolithotomy for definitive treatment.

Uric acid stones

About 5–10% of all stones are formed from uric acid. People with certain metabolic abnormalities, including obesity, may produce uric acid stones. Uric acid stones may form in association with conditions that cause hyperuricosuria (an excessive amount of uric acid in the urine) with or without high hyperuricemia (an excessive amount of uric acid in the serum). They may also form in association with disorders of acid/base metabolism where the urine is excessively acidic (low pH), resulting in precipitation of uric acid crystals. A diagnosis of uric acid urolithiasis is supported by the presence of a radiolucent stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples.

Other types

People with certain rare inborn errors of metabolism have a propensity to accumulate crystal-forming substances in their urine. For example, those with cystinuria, cystinosis, and Fanconi syndrome may form stones composed of cystine. People afflicted with xanthinuria often produce stones composed of xanthine. People afflicted with adenine phosphoribosyltransferase deficiency may produce 2,8-dihydroxyadenine stones, alkaptonurics produce homogentisic acid stones, and iminoglycinurics produce stones of glycine, proline and hydroxyproline. Urolithiasis has also been noted to occur in the setting of therapeutic drug use, with crystals of drug forming within the renal tract in some patients currently being treated with agents such as indinavir, sulfadiazine and triamterene.

Signs and symptoms

Signs of urolithiasis include oliguria (reduced urinary volume) caused by obstruction of the bladder or urethra by a stone or rarely, simultaneous obstruction of both ureters by two separate stones. Postrenal azotemia and hydronephrosis (distension and dilation of the renal pelvis and calyces)[  can be observed following the obstruction of urine flow through one or both ureters.[

Hallmark symptoms of kidney stones include renal colic, fever, hematuria, pyuria, and dysuria. Pain caused by kidney stones, referred to as renal colic, is often described as one of the strongest pain sensations felt by humans. Renal colic, which typically comes in waves lasting 20 to 60 minutes, is caused by peristaltic contractions of the ureter as it attempts to expel the stone. It typically begins in the flank or lower back, often radiating to the groin or in men, to the testes. The embryological link between the urinary tract, the genital system and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in nephrolithiasis and ureterolithiasis.

Causes

Supersaturation of urine

When the urine becomes supersaturated (when the urine solvent contains more solutes than it can hold in solution) with one or more crystal-forming substances, a seed crystal may form through the process of nucleation. Heterogeneous nucleation (where there is a solid surface present on which a crystal can grow) proceeds more rapidly than homogeneous nucleation (where a crystal must grow in liquid medium with no such surface), because it requires less energy. Adhering to cells on the surface of a renal papillae, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low.

Supersaturation of the urine with respect to a crystal-forming compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 mL. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 mL. One can readily see that the formation of uric acid stones requires a combination of hyperuricosuria (high urine uric acid levels) and low urine pH; hyperuricosuria alone is not associated with uric acid stone formation if the urine pH is alkaline. Supersaturation of the urine is a necessary but not a sufficient condition for the development of any urinary calculus. Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex etiology.

Inhibitors of stone formation

Normal urine contains chelating agents such as citrate that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include calgranulin (an S-100 calcium binding protein), Tamm-Horsfall protein (THP), glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin F1 peptide, and bikunin (uronic acid-rich protein). The biochemical mechanisms of action of these substances have not yet been thoroughly elucidated. However, when these substances fall below their normal proportions, stones can form out of an aggregation of crystals.

Kidney stones often result from a combination of factors, rather than a single, well-defined cause. Stones are more common in people whose diet is very high in animal protein or vitamin C or who do not consume enough water or calcium. They can result from an underlying metabolic condition, such as renal tubular acidosis, Dent's disease, hyperparathyroidism, primary hyperoxaluria or medullary sponge kidney.  Kidney stones are also more common in patients with Crohn's disease.[27] Patients with recurrent kidney stones are often screened for these disorders. This is typically done with a 24–hour urine collection that is chemically analyzed for deficiencies and excesses that promote stone formation.

Calcium

Some studies suggest that people who take supplemental calcium have a higher risk of developing kidney stones, and these findings have been used as the basis for setting the Recommended Daily Intake (RDI) for calcium in adults. In the Women's Health Initiative, postmenopausal women who consumed 1,000 milligrams of supplemental calcium and 400 IU of vitamin D per day for 7 years had a 17% higher risk of developing kidney stones than subjects taking a placebo. The Nurses' Health Study also showed an association between supplemental calcium intake and kidney stone formation.

Unlike supplemental calcium, high intakes of dietary calcium do not appear to cause kidney stones and may actually protect against their development. This is perhaps related to the role of calcium in binding ingested oxalate in the gastrointestinal tract. As the amount of calcium intake decreases, the amount of oxalate available for absorption into the bloodstream increases; this oxalate is then excreted in greater amounts into the urine by the kidneys. In the urine, oxalate is a very strong promoter of calcium oxalate precipitation, about 15 times stronger than calcium. In fact, current evidence suggests that the consumption of diets low in calcium is associated with a higher overall risk for the development of kidney stones. For most individuals however, other risk factors for kidney stones, such as high intakes of oxalates from food and low intakes of fluid, probably play a bigger role than calcium intake.

Role of dietary animal protein

Diets in Western nations typically contain more animal protein than the body needs, and as the excess amino acids are broken down and excreted, the sulfurous amino acids (typically derived from animal rather than vegetarian foods) cause calcium to be excreted in the urine; calcium is one component of the most common type of human kidney stones, calcium oxalate. Red meat also contains acids that need to be excreted and this acidity constitutes another risk factor for kidney stones. High intake of animal protein also presents a greater uric acid load to be excreted by the kidney. This in turn acidifies the urine, increasing the risk of uric acid stones. In either case, the body often balances this acidic urinary pH by leaching calcium from the bones.

Other

There is some evidence that water fluoridation may increase the risk of kidney stone formation. In one study, patients with symptoms of skeletal fluorosis were 4.6 times as likely to develop kidney stones.

Despite a widely-held belief in the medical community that ingestion of vitamin C supplements is associated with an increased incidence of kidney stones, the evidence for a causal relationship between vitamin C supplements and kidney stones is inconclusive.

There are no conclusive data demonstrating a cause and effect relationship between alcohol consumption and kidney stones. However, some have theorized that certain behaviors associated with frequent and binge drinking can lead to systemic dehydration, which can in turn lead to the development of kidney stones.[43]

The American Urological Association has projected that increasing global temperatures will lead to an increased incidence of kidney stones in the United States by expanding the "kidney stone belt" of the southern United States. Astronauts seem to show a higher risk of developing kidney stones during or after space flights of long duration.

Prevention

Specific therapy should be tailored to the type of stones involved. Dietary intake can have a profound influence on the development of kidney stones. Preventive strategies may include dietary modifications and medication with the goal of reducing the excretory load on the kidneys.

A key principle for the prevention of kidney stones is to increase urine volume. The relative probability of kidney stone formation decreases as urinary volume increases. Because of this, maintenance of dilute urine by means of vigorous fluid therapy is beneficial in all forms of nephrolithiasis. Fluid intake should be sufficient to maintain a urine output of 2–3 liters per day. A high fluid intake has been associated with a 40% reduction in recurrence risk.

Available data suggest that the type of fluid ingested is important. For example, orange juice may help prevent calcium oxalate stone formation, blackcurrant juice may help prevent uric acid stones, and cranberry juice may help with struvite stones. Lemons have the highest concentration of citrate of any citrus fruit, and daily consumption of lemonade has been shown to decrease the rate of stone formation. Beer appears to decrease the rate of stone formation, while grapefruit juice appears to increase the risk. One study indicated that intake of caffeinated beverages increases risk of kidney stones. While it may be advised to avoid caffeinated cola beverages because of their high phosphate content, this does not include coffee or tea. In fact, prospective cohort studies of coffee and tea actually indicate that they may prevent kidney stones. Though caffeine does acutely increase urinary calcium excretion, several independent epidemiologic studies have shown that coffee intake overall is protective against the formation of stones.

Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream. A randomized controlled trial published in 2002 assigned men with hypercalciuria to follow either a diet containing a normal amount of calcium (30 mmol per day) but with restricted intake of animal protein and salt, or a low-calcium (10 mmol per day) diet. At 5 years, the group on the normal calcium, low animal protein and low salt diet had a 51% lower rate of stone recurrence than those following a low-calcium diet. Some nephrologists and urologists recommend chewing calcium tablets during meals containing oxalate foods. Calcium citrate supplements can be taken with meals if dietary calcium cannot be increased by other means. The preferred calcium supplement for people at risk of stone formation is calcium citrate because it helps to increase urinary citrate excretion.

Aside from vigorous oral hydration and consumption of more dietary calcium, prevention strategies include avoidance of large doses of vitamin C and restriction of oxalate-rich foods. Measurements of food oxalate content have been difficult and issues remain about the proportion of oxalate that is bioavailable, versus a proportion that is not absorbed by the intestine. Oxalate-rich foods are usually restricted to some degree, particularly in patients with high urinary oxalate levels, but no randomized controlled trial of oxalate restriction has been performed to test that hypotheses.


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Papaya

The papaya (from Carib via Spanish), papaw, or pawpaw is the fruit of the plant Carica papaya, the sole species in the genus Carica of the plant family Caricaceae. It is native to the tropics of the Americas, and was first cultivated in Mexico several centuries before the emergence of the Mesoamerican classic cultures.

The papaya is a large tree-like plant, with a single stem growing from 5 to 10 metres (16 to 33 ft) tall, with spirally arranged leaves confined to the top of the trunk. The lower trunk is conspicuously scarred where leaves and fruit were borne. The leaves are large, 50–70 centimetres (20–28 in) diameter, deeply palmately lobed with 7 lobes. The tree is usually unbranched, unless lopped. The flowers are similar in shape to the flowers of the Plumeria, but are much smaller and wax-like. They appear on the axils of the leaves, maturing into the large 15–45 centimetres (5.9–18 in) long, 10–30 centimetres (3.9–12 in) diameter fruit. The fruit is ripe when it feels soft (like a ripe avocado or a bit softer) and its skin has attained an amber to orange hue.

Common names

Carica papaya plants, and their fruits, are generally known as papayas. However, the papaya is also commonly called pawpaw or papaw, although in North America the term pawpaw usually refers to plants in the unrelated North American genus Asimina, especially A. triloba, which produces large, edible fruits. The papaya is also sometimes called mugua, a name used in traditional Chinese medicine for Chaenomeles speciosa (flowering quince) or Pseudocydonia sinensis (Chinese quince). In the Dominican Republic, the papaya is usually called "lechoza", a name associated with the plant's milky sap.

Cultivation

Originally from southern Mexico (particularly Chiapas and Veracruz), Central America, and northern South America, the papaya is now cultivated in most tropical countries. In cultivation, it grows rapidly, fruiting within 3 years. It is, however, highly frost sensitive, limiting papaya production to tropical lands.

In the 1990s, the papaya ringspot virus threatened to wipe out Hawaii’s papaya industry completely. Cultivars that had been genetically modified to be resistant to the virus (including 'SunUp' and 'Rainbow'), were then introduced there. There is still no conventional or organic method of controlling the ringspot virus. In 2004, it was found that papayas throughout Hawaii had experienced hybridization with the genetically modified varieties and that many seed stocks were contaminated. By 2010, 80% of Hawaiian papaya plants were genetically modified

Cultivars

Two kinds of papayas are commonly grown. One has sweet, red (or orangish) flesh, and the other has yellow flesh; in Australia these are called "red papaya" and "yellow papaw", respectively. Either kind, picked green, is called a "green papaya."

The large-fruited, red-fleshed 'Maradol', 'Sunrise', and 'Caribbean Red' papayas often sold in U.S. markets are commonly grown in Mexico and Belize.

'SunUp' and 'Rainbow', grown in Hawaii, are genetically modified to be resistant to the papaya ringspot virus.

Uses

Papayas can be used as a food, a cooking aid, and in medicine. The stem and bark are also used in rope production.

Gastronomy

The ripe fruit of the papaya is usually eaten raw, without skin or seeds. The unripe green fruit can be eaten cooked, usually in curries, salads, and stews. Green papaya is used in south east Asian cooking, both raw and cooked. Papayas have a relatively high amount of pectin, which can be used to make jellies.

The black seeds of the papaya are edible and have a sharp, spicy taste. They are sometimes ground and used as a substitute for black pepper.

In some parts of Asia, the young leaves of papaya are steamed and eaten like spinach. In some parts of the world, papaya leaves are made into tea as a preventative for malaria, although there is no scientific evidence for the effectiveness of this treatment.

Meat tenderizing

Green papaya fruit and the tree's latex are both rich in an enzyme called papain, a protease which is useful in tenderizing meat and other proteins. Its ability to break down tough meat fibers was used for thousands of years by indigenous Americans. It is now included as a component in powdered meat tenderizers.

Folk medicine

Papaya is marketed in tablet form to remedy digestive problems.

Papain is also applied topically (in countries where it grows) for the treatment of cuts, rashes, stings and burns. Papain ointment is commonly made from fermented papaya flesh, and is applied as a gel-like paste. Harrison Ford was treated for a ruptured disc incurred during filming of Indiana Jones and the Temple of Doom by papain injections.

Women in India, Bangladesh, Pakistan, Sri Lanka, and other countries have long used green papaya as a folk remedy for contraception and abortion. Enslaved women in the West Indies were noted for consuming papaya to prevent pregnancies and thus preventing their children from being born into slavery. Medical research in animals has confirmed the contraceptive and abortifacient capability of papaya, and also found that papaya seeds have contraceptive effects in adult male langur monkeys, and possibly in adult male humans, as well. Unripe papaya is especially effective in large amounts or high doses. Ripe papaya is not teratogenic and will not cause miscarriage in small amounts. Phytochemicals in papaya may suppress the effects of progesterone.

Allergies and side effects

Papaya is frequently used as a hair conditioner, but should be used in small amounts. Papaya releases a latex fluid when not quite ripe, which can cause irritation and provoke allergic reaction in some people. The papaya fruit, seeds, latex, and leaves also contains carpaine, an anthelmintic alkaloid (a drug that removes parasitic worms from the body), which can be dangerous in high doses.

It is speculated that the latex concentration of unripe papayas may cause uterine contractions, which may lead to a miscarriage. Papaya seed extracts in large doses have a contraceptive effect on rats and monkeys, but in small doses have no effect on the unborn animals.

Excessive consumption of papaya can cause carotenemia, the yellowing of soles and palms, which is otherwise harmless. However, a very large dose would need to be consumed; papaya contains about 6% of the level of beta carotene found in carrots (the most common cause of carotenemia)

Medicinal potential

The juice has an in vitro antiproliferative effect on liver cancer cells, probably due to its component of lycopene[18] or immune system stimulation.

Papaya seed could be used as an antibacterial agent for Escherichia coli, Staphylococcus aureus or Salmonella typhi, although further research is needed before advocating large-scale therapy.

Papaya seed extract may be nephroprotective (protect the kidneys) in toxicity-induced kidney failure

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