Hong Kong Flu

Compiled and Summarized by Anthony
Hong Kong flu is a pandemic of influenza A (H3N2) in 1968-69. This virus was first detected in Hong Kong in early 1968 and spread to the United States later that year. where it caused about 34,000 deaths, making it the mildest pandemic in the 20th century. Also known as Hong Kong influenza.

There could be several reasons why fewer people in the US died due to this virus. First, the Hong Kong flu virus was similar in some ways to the Asian flu virus that circulated between 1957 and 1968. Earlier infections by the Asian flu virus might have provided some immunity against the Hong Kong flu virus that may have helped to reduce the severity of illness during the Hong Kong pandemic.

Second, instead of peaking in September or October, like pandemic influenza had in the previous two pandemics, this pandemic did not gain momentum until near the school holidays in December. Since children were at home and did not infect one another at school, the rate of influenza illness among schoolchildren and their families declined.

Third, improved medical care and antibiotics that are more effective for secondary bacterial infections were available for those who became ill.

Signs and Symptoms

The list of signs and symptoms mentioned in various sources for Flu includes the 20 symptoms listed below:

· Headache
· Fever
· Chills
· Sneezing
· Runny nose
· Nasal inflammation
· Blocked nose
· Dry cough
· Sore throat
· Sweating
· Body aches
· Muscle aches
· Limb pain
· Joint pain
· Loss of appetite
· Prostration
· Exhaustion
· Fatigue
· Weakness
· Myalgia

Note that Flu symptoms usually refers to various symptoms known to a patient, but the phrase Flu signs may refer to those signs only noticeable by a doctor.

Causative Agent

Influenza A (H3N2)

Mode of Transmission

H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtype arose in pigs co-infected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported re-assortment of divergent subtypes. However, other hosts appear capable of similar co-infection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible.

As an Influenza virus, it predominately transmitted by airborne spread in aerosols but can also be transferred by direct contact with droplets. Nasal inoculation after hand contamination with the virus is also an important mode of transmission.

Direct contact is important, as the virus will survive some hours in dried mucus particularly in cold and dry environments.

Diagnosis

Laboratory diagnosis depends upon the demonstration of the virus or its components or a rising antibody titre. The following tests are available:

· Direct antigen detection
· RT-PCR for viral RNA
· Virus culture
(nasal pharyngeal aspirate preferably within 3 days of onset, other specimens, such as stool and rectal swabs may be considered.)

· Serological tests for detection of specific antibody.
(blood test within 7 days of onset and repeated at least 2 weeks after onset.)

Incubation Period

The incubation period of a case will probably be one to four days.

Pathogenesis

Infection of pigs with influenza A viruses is of substantial importance to the swine industry and to the epidemiology of human influenza. At present, three main subtypes of influenza viruses are circulating in the swine population throughout the world: subtypes H1N1, H3N2, and H1N2. In North America, influenza virus outbreaks among pigs have historically been due almost exclusively to infection with H1N1 viruses. Since 1997-1998, however, H3N2 viruses have emerged and spread widely within the swine population. Triple-reassortant H3N2 viruses containing hemagglutinin (HA), neuraminidase (NA), and PB1 polymerase genes of human influenza virus origin, the matrix (M), nucleoprotein (NP), and nonstructural (NS) genes of classical swine influenza virus origin, and the PA and PB2 polymerase genes of avian influenza virus origin have been isolated widely throughout the United States. These viruses have been associated with outbreaks of respiratory disease in pigs of all ages and abortions in pregnant sows. In addition, reassortment between these viruses and classical H1N1 viruses has led to the subsequent development of H1N2 viruses, which have also spread throughout the swine population of the United States. In contrast, an H3N2 virus in which all eight RNA segments were of human influenza virus origin was isolated from a single baby pig in 1997 on a farm in Ontario, Canada. This virus did not spread within the farm of origin and has not been recovered from pigs subsequent to its initial isolation.

Influenza A viruses have been isolated from various species, including humans, pigs, horses, birds, sea mammals, and mink. However, wild waterfowl serve as the reservoir from which all influenza viruses are thought to have emerged. Despite their common origin, influenza A viruses are generally restricted in host range. In particular, avian influenza viruses replicate poorly in humans and nonhuman primates and human influenza viruses do not replicate well in birds. In contrast, swine influenza viruses have been shown repeatedly to infect humans as zoonotic infections, and conversely, human influenza viruses have also been isolated from pigs.

The host range restriction of influenza viruses is a polygenic trait, but the HA gene is considered to be a particularly important determinant since HA is responsible for attachment of the virus to sialic acid receptors on the host cell surface. While human influenza viruses preferentially bind to sialic acid bound to galactose by α2,6 linkages, avian viruses preferentially recognize sialic acid bound by α2,3 linkages. This is consistent with the fact that human tracheal epithelial cells predominantly express α2,6-linked receptors, whereas avian intestinal cells predominantly express α2,3-linked receptors. However, avian and human influenza viruses can both infect pigs because porcine respiratory epithelial cells express both N-acetylneuraminic acid-α2,3-galactose and N-acetylneuraminic acid-α2,6-galactose. Pigs can therefore function as intermediate “mixing vessel” hosts in establishing new influenza virus lineages by supporting coinfection, replication, and reassortment among human, avian, and swine influenza viruses.

Even though influenza viruses can cross species barriers and infect pigs, it is not known what properties are necessary to allow a virus to form a stable lineage and to spread efficiently within the pig population. In particular, a wholly human H3N2 virus, A/Swine/Ontario/00130/97 (H3N2) (Sw/ONT), initially crossed the species barrier to infect a pig in Canada in 1997, but it did not infect other pigs in the herd. Its disappearance may have been due to characteristics of the virus (i.e., its replication efficiency in pigs) or epidemiological factors (i.e., the availability of susceptible animals). In contrast, triple-reassortant H3N2 viruses containing genes from human, classical swine, and avian influenza viruses have spread throughout the swine population of the United States since 1998. The critical factors that affect replication ability in pigs may include the overall constellation of genes present in the triple-reassortant viruses. However, we have also identified specific differences in the sequences of the HA genes of triple-reassortant viruses that may represent swine adaptation mutations. As an initial step in understanding the pathogenesis of these viruses in pigs, the present study was designed to define the specific characteristics of these viruses, including their infectivities, replication kinetics, and ability to induce pathological lesions under experimental infection conditions.

Pathophysiology

Influenza virus infection occurs after transfer of respiratory secretions from an infected individual to a person who is immunologically susceptible. If not neutralized by secretory antibodies, the virus invades airway and respiratory tract cells. Once within host cells, cellular dysfunction and degeneration occur, along with viral replication and release of viral progeny. Systemic symptoms result from inflammatory mediators, similar to other viruses.

Prevention

Please see Flu -Prevention.

Treatment

Please see Flu -Treatment.

Complications

The most common complication of Influenza is Pneumonia. Other complications include Bronchitis, Sinus, Ear infections, Myocarditis, and Pericarditis. Myositis is among the complications but this one rarely occurs.

References

http://www.medterms.com
Provided primary source of information.

http://wrongdiagnosis.com
Provided information on Signs and Symptoms.

http://en.wikipedia.org
Provided extra information.

http://www3.hku.hk
Provided extra information.

http://www.pubmedcentral.nih.gov
Provided information on Pathogenesis.

If you find an error, please let us know.

Prostate Cancer

Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. It occurs when cells of the prostate mutate and begin to multiply out of control. These cells may spread (metastasize) from the prostate to other parts of the body, especially the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, erectile dysfunction and other symptoms.

Rates of prostate cancer vary widely across the world. Although the rates vary widely between countries, it is least common in South and East Asia, more common in Europe, and most common in the United States. According to the American Cancer Society, prostate cancer is least common among Asian men and most common among black men, with figures for white men in-between. However, these high rates may be affected by increasing rates of detection.

Prostate cancer develops most frequently in men over fifty. This cancer can occur only in men, as the prostate is exclusively of the male reproductive tract. It is the most common type of cancer in men in the United States, where it is responsible for more male deaths than any other cancer, except lung cancer. However, many men who develop prostate cancer never have symptoms, undergo no therapy, and eventually die of other causes. Many factors, including genetics and diet, have been implicated in the development of prostate cancer.

Prostate cancer is most often discovered by physical examination or by screening blood tests, such as the PSA (prostate specific antigen) test. There is some current concern about the accuracy of the PSA test and its usefulness. Suspected prostate cancer is typically confirmed by removing a piece of the prostate (biopsy) and examining it under a microscope. Further tests, such as X-rays and bone scans, may be performed to determine whether prostate cancer has spread.

Signs and Symptoms

Early prostate cancer usually causes no symptoms. Often it is diagnosed during the workup for an elevated PSA noticed during a routine checkup. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hypertrophy. These include frequent urination, increased urination at night, difficulty starting and maintaining a steady stream of urine, blood in the urine, and painful urination. Prostate cancer may also cause problems with sexual function, such as difficulty achieving erection or painful ejaculation.

Advanced prostate cancer may cause additional symptoms as the disease spreads to other parts of the body. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis or ribs, from cancer which has spread to these bones. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.

Causes

The cause of prostate cancer isn't fully understood at present. But there are certain factors that make prostate cancer more likely, which are listed below.

* The risk of prostate cancer increases steadily with age and it is rare in men under 50.
* Your risk is higher if you have close relatives (a father, uncle or brother) who have had prostate cancer.
* If several women in your family have had breast cancer (especially if they were diagnosed at under 40 years of age) an inherited faulty gene may be present. The gene may also increase the risk of the men in that family getting prostate cancer.
* If you are African-Caribbean or African-American you are at highest risk whereas if you are Asian, you are at lower risk.
* A high fat diet may increase your risk.

Diagnosis

When a man has symptoms of prostate cancer, or a screening test indicates an increased risk for cancer, more invasive evaluation is offered.

The only test which can fully confirm the diagnosis of prostate cancer is a biopsy, the removal of small pieces of the prostate for microscopic examination. However, prior to a biopsy, several other tools may be used to gather more information about the prostate and the urinary tract. Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted down the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum.

Biopsy

If cancer is suspected, a biopsy is offered. During a biopsy a urologist obtains tissue samples from the prostate via the rectum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Fifty-five percent of men report discomfort during prostate biopsy.

Gleason score

The tissue samples are then examined under a microscope to determine whether cancer cells are present, and to evaluate the microscopic features (or Gleason score) of any cancer found.

Tumor markers

Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of malignant cells that have metastasized.

New tests being investigated

Currently, an active area of research involves non-invasive methods of prostate tumor detection. Adenoviruses modified to transfect tumor cells with harmless yet distinct genes (such as luciferase) have proven capable of early detection. So far, though, this area of research has only been tested in animal and LNCaP models.

PCA3

Another potential non-invasive methods of early prostate tumor detection is through a molecular test that detects the presence of cell-associated PCA3 mRNA in urine. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. PCA3 is not a replacement for PSA but an additional tool to help decide if, in men suspected of having prostate cancer, a biopsy is really needed. The higher the expression of PCA3 in urine, the greater the likelihood of a positive biopsy, i.e. the presence of cancer cells in the prostate. Company Diagnocure has an exclusive worldwide license for all diagnostic and therapeutic applications related to PCA3

Early prostate cancer

It was reported in April 2007 that a new blood test for early prostate cancer antigen-2 (EPCA-2) is being researched that may alert men if they have prostate cancer and how aggressive it will be.

Pathogenesis/Pathophysiolgy

Genetics play some role in risk of prostate cancer. Specifically, around 9% of prostate cancers appear to be familial.

The male hormone, testosterone, and its analogues are definitely involved in the pathogenesis of prostate cancer. The National Cancer Institute lists the following as support for the role of male sex hormones in prostate cancer.

· Neither benign prostatic hypertrophy (BPH) nor prostate cancer have been reported in men castrated prior to puberty.

· Many studies have shown that populations with higher levels of testosterone and most importantly dihydrotestosterone have higher incidences of prostate cancer. For example the highest levels are found in blacks males, intermediate levels in white males, and lowest levels in native Japanese. The incidence of prostate cancer parallels the levels.

· Deprivation of androgens (males sex hormones) leads to decreased levels of PSA, and death of prostate cancer cells.

Dietary fat appears to play a role in prostate cancer but studies are conflicting. If dietary fat is a risk factor, it appears that saturated fat from animal origins is a greater risk factor than unsaturated fat from vegetable origin. The mechanism by which fat may be involved in prostate cancer has been hypothesized. First, dietary fat increases serum levels of male sex hormones (androgens). Some studies indicate that omega 3 oils (fish oil, flaxseed oil) may actually prevent prostate cancer. Finally, many studies have found that there is a relationship between the amount of fat eaten by the mother during pregnancy and the later development of prostate cancer in her male offspring.

Previous articles have outlined the benefits of eating a Mediterranean style diet, consisting of plenty of fresh fruits and vegetables, fish, and olive oil. This type of diet has benefits for cardiovascular health, and appears to be advisable for prevention of cancers of all types.

Finally, there is some evidence that exposure to pesticides and heavy metals may be a risk factor for prostate cancer. Specifically there may be a relationship between dioxin (a contaminant of herbicides) and prostate cancer. Likewise, the metal cadmium found in NiCad batteries is suspect. Workers in plants that manufacture or recycle these batteries should take extreme precautions to prevent exposure.

Prostate cancer develops when the rates of cell division and cell death are no longer equal, leading to uncontrolled tumor growth. Following the initial transformation event, further mutations of a multitude of genes, including the genes for p53 and retinoblastoma, can lead to tumor progression and metastasis. Most prostate cancers are adenocarcinomas (95%).

Approximately 4% of cases of prostate cancer have transitional cell morphology and are thought to arise from the urothelial lining of the prostatic urethra. Few cases have neuroendocrine morphology. When present, they are believed to arise from the neuroendocrine stem cells normally present in the prostate or from aberrant differentiation programs during cell transformation.

Of cases of prostate cancer, 70% arise in the peripheral zone, 15-20% arise in the central zone, and 10-15% arise in the transitional zone. Most prostate cancers are multifocal, with synchronous involvement of multiple zones of the prostate, which may be due to clonal and nonclonal tumors.

Natural history

The natural history is still relatively unknown, and many aspects of progression are poorly understood. Symptoms or abnormal DRE findings in the pre-PSA era only brought 40-50% of patients with prostate cancer to medical attention, and these patients usually had locally advanced disease. The advent of PSA testing has helped identify patients with less-advanced, organ-confined disease.

Evidence suggests that most prostate cancers are multifocal and heterogeneous. Cancers can start in the transitional zone or, more commonly, the peripheral zone. When these cancers are locally invasive, the transitional zone tumors spread to the bladder neck, while the peripheral zone tumors extend into the ejaculatory ducts and seminal vesicles. Penetration through the prostatic capsule and along the perineural or vascular spaces is a relatively late event.

The mechanism for distant metastasis is poorly understood. The cancer spreads to bone early, occasionally without significant lymphadenopathy. Currently, 2 predominant theories have been proposed for spread, the mechanical theory and the seed-and-soil theory.

* The mechanical theory involves direct spread through the lymphatics and venous spaces into the lower lumbar spine.

* Advocates of the seed-and-soil theory believe tissue factors must be present that allow for preferential growth in certain tissues, such as the bone. Lung, liver, and adrenal metastases have also been documented. Specific tissue growth factors and extracellular matrices are possible examples.

The doubling time in early-stage disease is as slow as 2-4 years, but this changes as the tumor grows and becomes more aggressive. Larger tumors usually have a higher Gleason grade and a faster doubling time.

Natural history by stage

* T1a - Progression over 10 years (uncommon)

* T1b - Tumor-related death rate of 10% in 10 years

* T2 - Ten-year metastasis-free survival rate of 81% with grade 1, 58% with grade 2, and 26% with grade 3

* T3 - Lymph node metastasis at presentation in 50% and approximately 25% rate of 10-year disease-free survival

The natural history of clinically localized disease is variable, with lower-grade tumors having a more indolent course, while some high-grade lesions progress to metastatic disease with relative rapidity. Several studies have examined the cancer-specific and quality-of-life outcomes associated with a watchful waiting approach to localized disease.

* Albertsen et al followed patients who received no initial treatment for prostate cancer. As disease progression occurred, many received antiandrogens. Men with poorly differentiated tumors lost 6-8 years of life, while those with moderately differentiated tumors lost 4-5 years. Of all men followed for 10 years, 40% died of causes other than prostate cancer. This study was performed prior to PSA screening.

* Graversen et al compared watchful waiting with radical prostatectomy. They found no overall difference in survival, but they did find that a high Gleason score was associated with poor survival in both groups.

* Chodak et al confirmed this finding by analyzing 6 studies and finding a 34% survival rate with grade 3 tumors versus an 87% disease-specific survival rate for grade 1 and 2 tumors. The metastasis-free survival rate also significantly dropped as the grade progressed from 1 to 3.

* Johansson reported their recent update on a population-based cohort study with a mean observation period of 21 years. In this study, 223 patients with early-stage, initially untreated prostatic cancer were observed. Patients with tumor progression received hormonal treatment (orchiectomy or estrogens) if they had symptoms. Thirty-nine (17%) experienced metastatic disease, with most cancers having an indolent course during the first 10-15 years. However, further follow-up at 15-20 years revealed a substantial decrease in cumulative progression-free survival (from 45% to 36%), survival without metastases (from 76.9% to 51.2%), and prostate cancer–specific survival (from 78.7% to 54.4%). Prostate cancer mortality increased from 15 deaths per 1000 person-years during the first 15 years to 44 deaths per 1000 person-years beyond 15 years of follow-up.

Taken together, these data suggest that although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. In addition, these findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years.

Prevention

Several medications and vitamins may also help prevent prostate cancer. Two dietary supplements, vitamin E and selenium, may help prevent prostate cancer when taken daily. Estrogens from fermented soybeans and other plant sources (called phytoestrogens) may also help prevent prostate cancer. The selective estrogen receptor modulator drug toremifene has shown promise in early trials. Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride, and dutasteride, have also shown some promise. The use of these medications for primary prevention is still in the testing phase, and they are not widely used for this purpose. The problem with these medications is that they may preferentially block the development of lower-grade prostate tumors, leading to a relatively greater chance of higher grade cancers, and negating any overall survival improvement. Green tea may be protective (due to its polyphenol content), though the data is mixed. A 2006 study of green tea derivatives demonstrated promising prostate cancer prevention in patients at high risk for the disease. In 2003, an Australian research team led by Graham Giles of The Cancer Council Australia concluded that frequent masturbation by males appears to help prevent the development of prostate cancer. Recent research published in the Journal of the National Cancer Institute suggests that taking multivitamins more than seven times a week can increase the risks of contracting the disease. This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label. Scientists recommend a healthy, well balanced diet rich in fiber, and to reduce intake of meat. A 2007 study published in the Journal of the National Cancer Institute found that men eating cauliflower, broccoli, or one of the other cruciferous vegetables, more than once a week were 40% less likely to develop prostate cancer than men who rarely ate those vegetables. Scientists believe the reason for this phenomenon has to do with a phytochemical called Diindolylmethane in these vegetables that has anti-androgenic and immune modulating properties. This compound is currently under investigation by the National Cancer Institute as a natural therapeutic for prostate cancer.

Capsaicin

Capsaicin, the chemical found in peppers, has been shown to cause 80% of cancerous prostate cells to undergo apoptosis in mice. For prostate cancer cells whose growth is dependent upon testosterone, Capsaicin curbed the proliferation of such cells by freezing the cells in a non-proliferate state, and cancerous prostate cells that are androgen independent "suicided" as well.

"Capsaicin had a profound anti-proliferative effect on human prostate cancer cells in culture," said Sören Lehmann, M.D., Ph.D., visiting scientist at the Cedars-Sinai Medical Center and the UCLA School of Medicine. "It also dramatically slowed the development of prostate tumors formed by those human cell lines grown in mouse models."

Peppers which rank higher on the Scoville scale and thus have a higher piquancy contain a higher amount of Capsaicin. Habaneros, for example, have a Scoville rating of over 300,000, while red chili peppers have a rating of 5,000. While the UCLA and Samuel Oschin Comprehensive Cancer Institute studies show promising implications, the same effects have not yet been duplicated in men.

Treatment

Treatment for prostate cancer may involve watchful waiting, surgery, radiation therapy, High Intensity Focused Ultrasound (HIFU), chemotherapy, cryosurgery, hormonal therapy, or some combination. Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are the man's age, his general health, and his feelings about potential treatments and their possible side effects. Because all treatments can have significant side effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

The selection of treatment options may be a complex decision involving many factors. For example, radical prostatectomy after primary radiation failure is a very technically challenging surgery and may not be an option. This may enter into the treatment decision.

If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors who treat prostate cancer use a variety of nomograms to predict the probability of spread. Treatment by watchful waiting, HIFU, radiation therapy, cryosurgery, and surgery are generally offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for disease which has spread beyond the prostate. However, there are exceptions: radiation therapy may be used for some advanced tumors, and hormonal therapy is used for some early stage tumors. Cryotherapy, hormonal therapy, and chemotherapy may also be offered if initial treatment fails and the cancer progresses.

Complications

The list of complications that have been mentioned in various sources for Prostate Cancer includes:

* Metastatic cancer
* Bone pain

Complications and sequelae of Prostate Cancer include:

* Red cell production reduced
* Osteosclerosis
* Prostate specific antigen levels raised (plasma or serum)
* Back pain
* Bone pain
* Hematospermia
* Bone metastases
* Incontinence, urine
* Urethral stricture
* Hematuria
* Pathological fracture
* Acid phosphatase levels raised (plasma or serum)

References

http://www.wikipedia.org
Served as primary source.

http://www.alternative-cancer-treatments.com
Provided additional information.

http://hcd2.bupa.co.uk
Provided extra reference.

http://www.emedicine.com
Provided complete information and extra reference.

http://www.wrongdiagnosis.com
Provided extra references.

If you find an error, please contact us.

Breast Cancer

Compiled and Summarized by Anthony
Worldwide, breast cancer is the fifth most common cause of cancer death (after lung cancer, stomach cancer, liver cancer, and colon cancer). In 2005, breast cancer caused 502,000 deaths (7% of cancer deaths; almost 1% of all deaths) worldwide. Among women worldwide, breast cancer is the most common cause of cancer death.

In the United States, breast cancer is the third most common cause of cancer death (after lung cancer and colon cancer). In 2007, breast cancer is expected to cause 40,910 deaths (7% of cancer deaths; almost 2% of all deaths) in the U.S. Among women in the U.S., breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer). Women in the U.S. have a 1 in 8 lifetime chance of developing invasive breast cancer and a 1 in 33 chance of breast cancer causing their death. In the U.S., both incidence and death rates for breast cancer have been declining in the last few years. Nevertheless, a U.S. study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease, even though heart disease is a much more common cause of death among women.

The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world. Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males, though it is less common.

Signs and Symptoms

Early breast cancer can, in some cases, present as breast pain (mastodynia) or a painful lump. Since the advent of breast mammography, breast cancer is most frequently discovered as an asymptomatic nodule on a mammogram, before any symptoms are present. A lump under the arm or above the collarbone that does not go away may be present.

When breast cancer has invaded the dermal lymphatics - small lymph vessels of the skin, its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer. In inflammatory breast cancer, the breast cancer is blocking lymphatic vessels and this can cause pain, swelling, warmth, and redness throughout the breast, as well as an orange peel texture to the skin referred to as peau d'orange. Although there may have been no previous signs of breast cancer and the cancer might be missed in screening mammograms, Inflammatory Breast Cancer is at least locally advanced at presentation (LABC) and Stage IIIB. Immediate staging tests are required to rule out distant metastes which might already be present making it Stage IV.

Changes in the appearance or shape of the breast can raise suspicions of breast cancer.

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes at the nipple, and is a late manifestation of an underlying breast cancer.

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

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. More 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. Pleural effusions are not uncommon with metastatic breast cancer. Obviously, these symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.

Causes

Many women who develop breast cancer have no risk factors other than age and sex.

* Gender is the biggest risk because breast cancer occurs mostly in women.

* Age is another critical factor. Breast cancer may occur at any age, though the risk of breast cancer increases with age. The average woman at age 30 years has one chance in 280 of developing breast cancer in the next 10 years. This chance increases to one in 70 for a woman aged 40 years, and to one in 40 at age 50 years. A 60-year-old woman has a one in 30 chance of developing breast cancer in the next 10 years.

* White women are slightly more likely to develop breast cancer than African American women in the U.S.

* A woman with a personal history of cancer in one breast has a three- to fourfold greater risk of developing a new cancer in the other breast or in another part of the same breast. This refers to the risk for developing a new tumor and not a recurrence (return) of the first cancer.

Genetic Causes

Family history has long been known to be a risk factor for breast cancer. Both maternal and paternal relatives are important. The risk is highest if the affected relative developed breast cancer at a young age, had cancer in both breasts, or if she is a close relative. First-degree relatives, (mother, sister, daughter) are most important in estimating risk. Several second-degree relatives (grandmother, aunt) with breast cancer may also increase risk. Breast cancer in a male increases the risk for all his close female relatives. Having relatives with both breast and ovarian cancer also increases a woman's risk of developing breast cancer.

There is great interest in genes linked to breast cancer. About 5-10% of breast cancers are believed to be hereditary, as a result of mutations, or changes, in certain genes that are passed along in families.

* BRCA1 and BRCA2 are abnormal genes that, when inherited, markedly increase the risk of breast cancer to a lifetime risk estimated between 40 and 85%. Women with these abnormal genes also have an increased likelihood of developing ovarian cancer. Women who have the BRCA1 gene tend to develop breast cancer at an early age.

* Testing for these genes is expensive and may not be covered by insurance.

* The issues around testing are complicated, and women who are interested in testing should discuss this with their health-care providers.

Hormonal Causes

Hormonal influences play a role in the development of breast cancer.

* Women who start their periods at an early age (11 or younger) or experience a late menopause (55 or older) have a slightly higher risk of developing breast cancer. Conversely, being older at the time of the first menstrual period and early menopause tend to protect one from breast cancer.

* Having a child before age 30 years may provide some protection, and having no children may increase the risk for developing breast cancer.

* Oral contraceptives have not been shown to definitively increase or decrease a woman's lifetime risk of breast cancer.

* A large study conducted by the Women's Health Initiative showed an increased risk of breast cancer in postmenopausal women who were on a combination of estrogen and progesterone for several years. Therefore, women who are considering hormone therapy for menopausal symptoms need to discuss the risk versus the benefit with their health-care providers.

Lifestyle and Dietary Causes

Breast cancer seems to occur more frequently in countries with high dietary intake of fat, and being overweight or obese is a known risk factor for breast cancer, particularly in postmenopausal women.

* This link is thought to be an environmental influence rather than genetic. For example, Japanese women, at low risk for breast cancer while in Japan, increase their risk of developing breast cancer after coming to the United States.

* Several studies comparing groups of women with high- and low-fat diets, however, have failed to show a difference in breast cancer rates.

The use of alcohol is also an established risk factor for the development of breast cancer. The risk increases with the amount of alcohol consumed. Women who consume two to five alcoholic beverages per day have a risk about one and a half times that of nondrinkers for the development of breast cancer. Consumption of one alcoholic drink per day results in a slightly elevated risk.

Studies are also showing that regular exercise may actually reduce a woman's risk of developing breast cancer. Studies have not definitively established how much activity is needed for a significant reduction in risk. One study from the Women's Health Initiative (WHI) showed that as little as one and a quarter to two and a half hours per week of brisk walking reduced a woman's breast cancer risk by 18%.

Benign Breast Disease

* Fibrocystic breast changes are very common. Fibrocystic breasts are lumpy with some thickened tissue and are frequently associated with breast discomfort, especially right before the menstrual period. This condition does not lead to breast cancer.

* However, certain other types of benign breast changes, such as those diagnosed on biopsy as proliferative or hyperplastic, do predispose women to the later development of breast cancer.

Environmental Causes

Radiation treatment increases the likelihood of developing breast cancer but only after a long delay. For example, women who received radiation therapy to the upper body for treatment of Hodgkin disease before 30 years of age have a significantly higher rate of breast cancer than the general population.

Diagnosis

An abnormal area on a mammogram, a lump, or other changes in the breast can be caused by cancer or by other, less serious problems. To find out the cause of any of these signs or symptoms, a woman's doctor does a careful physical exam and asks about her personal and family medical history. In addition to checking general signs of health, the doctor may do one or more of the breast exams described below.

* Palpation. The doctor can tell a lot about a lump—its size, its texture, and whether it moves easily—by palpation, carefully feeling the lump and the tissue around it. Benign lumps often feel different from cancerous ones.

* Mammography. X-rays of the breast can give the doctor important information about a breast lump. If an area on the mammogram looks suspicious or is not clear, additional x-rays may be needed.

* Ultrasonography. Using high-frequency sound waves, ultrasonography can often show whether a lump is solid or filled with fluid. This exam may be used along with mammography.

Based on these exams, the doctor may decide that no further tests are needed and no treatment is necessary. In such cases, the doctor may need to check the woman regularly to watch for any changes. Often, however, the doctor must remove fluid or tissue from the breast to make a diagnosis.

Aspiration or needle biopsy. The doctor uses a needle to remove fluid or a small amount of tissue from a breast lump. This procedure may show whether a lump is a fluid-filled cyst (not cancer) or a solid mass (which may or may not be cancer). Using special techniques, tissue can be removed with a needle from an area that is suspicious on a mammogram but cannot be felt.

If tissue is removed in a needle biopsy, it goes to a lab to be checked for cancer cells. Clear fluid removed from a cyst may not need to be checked by a lab.

Surgical biopsy. The surgeon cuts out part or all of a lump or suspicious area. A pathologist examines the tissue under a microscope to check for cancer cells.

Pathogenesis/Pathophysiology

In a normal state, cells proliferate in response to external proliferation-promoting signals to fulfill a function such as replacing lost cells or repairing injured tissues. Once the goal has been reached, a set of proliferation-repressing signals is activated. These signals allow the cells to exit the proliferation cycle (cell cycle) by returning to the dormant state (G0), by differentiating, or by dying (apoptosis). Each of these functions is carried out by a complex system of interacting proteins. Constitutive expression by mutation or another genetic change of any component of the proliferation-promoting system may result in uncontrolled proliferation. The constitutively expressed component is called an oncogene.

Conversely, the loss by mutation or deletion of a proliferation-repressing gene results in an inability to stop the cell cycle and, thereby, continuous proliferation, possibly leading to cancer. The lost gene is called a tumor suppressor gene. Likewise, constitutive expression of antiapoptotic genes may result in immortalization of the cell, paving the way for further genetic changes and eventually cancer formation. Loss of proapoptotic genes may lead to similar results. Thus, autonomous proliferation and immortality shared by all cancers are the final result of successive genetic changes, which may be different from one cancer to another.

Breast cancer is not an exception in that regard. It is the result of multiple genetic changes that are different from those of other malignancies and that confer to this cancer its characteristic phenotype.

Cell-cycle deregulation in breast cancer

Estrogen and progesterone induce cyclin D1 and c-myc expression. Although both sex hormones provide directionality by shifting the CDKI p21 from CDK2 to CDK4, progesterone promotes maturation by inducing p27, while only estrogen allows multiple cycles. Recent studies have reported common amplification of cyclin D1 (a third of breast cancers), inactivation of p16, and mutation of TP53 in breast cancer.

c-myc overexpression is one of the most common genetic alterations encountered in persons with breast cancer (a third of patients). Depending on the availability of its different partners, it may result in proliferation and chromosomal instability (Myc-Max) or differentiation (Myc-Mad), probably by sequestering Myc and reducing its availability. Amplification of the c-myc gene is associated with a poor prognosis and a high S-phase.

Estrogen receptor (ER)–positive breast cancer cells undergo apoptosis after withdrawal of estrogen, suggesting that this hormone functions not only as a mitogen but also as a survival factor. The antiapoptotic factor Bcl-2 is commonly overexpressed in ER-positive breast cancers.

ER negativity is observed in a third of primary breast cancers and a third of recurrences of ER-positive primaries. The ER gene is usually intact with no identifiable deletions or mutations. Although the exact mechanism of this lack of expression is not known, hypermethylation used normally by the genome to silence certain genes is a possible explanation. Methylation of cytosine-rich areas (called CpG islands) of the ER-gene promoter region has been described in the majority of ER-negative breast cancers and in a small fraction of ER-positive breast cancers. Demethylation of these areas with specific agents (eg, 5-azacytidine) restores ER expression and its function in vitro.

A progesterone receptor (PR) is present in approximately 50% of all ER-positive tumors. Its presence depends on the expression of functional ER, which explains its absence in almost all ER-negative breast cancers. The mitogenic effect of progesterone in breast cancer may depend on the induction of local growth hormone production in the hyperplastic mammary epithelium. However, high doses of progestins have proven inhibitory effects on breast cancer growth mediated by the down-regulation of G1-phase CDKs and cyclin D1 leading to cell differentiation.

Regarding adhesion-dependent cell regulation, the transmembrane glycoproteins, ie, epithelial cadherins (E-cadherins), mediate with their extracellular domain cell-to-cell interactions, thus stabilizing the cell in the epithelial tissue. Their intracellular domain interacts with and controls the transcription factors B-catenins. A mutation or the absence of E-cadherins results in cell detachment, increased motility and invasiveness, and release of B-catenins, which up-regulates c-myc expression.

Expression of E-cadherins is down-regulated in breast cancer. Another family of adhesion molecules, the integrins, is involved in cell-to-matrix interactions. Integrins signal through the Fak-Src pathway, which activates PI3K and AKT, resulting in enhanced survival, proliferation, and motility. The main components of this pathway (Fak, PI3K, and AKT) are inhibited by PTEN (ie, phosphatase on chromosome 10 gene product, mutated in Cowden disease), which results in the suppression of survival and apoptosis.

The epidermal growth factor (EGF) receptor family plays a critical role in mammary tumorigenesis. Other than the EGF receptor itself, 3 other members of this family have been described, including c-erb-B2 (HER2, HER2/neu), c-erb-B3, and c-erb-B4; the latter is called a kinase-dead receptor because it does not carry a kinase function on the cytoplasmic domain of the receptor, which is in contrast to the other members of the family.

These receptors interact with many ligands, including EGF, transforming growth factor (TGF)–alpha, hergulin (or Neu differentiation factor), heparin-binding EGF-like growth factor, beta-cellulin, and epiregulin. Upon binding of a ligand with its cognate receptor, a homodimerization or heterodimerization process occurs, followed by autophosphorylation of the intracellular domain and activation of the intrinsic catalytic domain.

Transmission of the signal is operated via phosphorylation of adaptor proteins (GRB2-SOS, Shc, IRS-1/2, STAT) docked or recruited to the cytoplasmic domain of the receptor, followed by activation of the RAS-GTP protein, then 1 of 3 pathways to the nucleus (ie, Raf/MEK/ERK-1/2, MEKK1/MEK4/7/JNK, PI3K/AKT/GSK).

Transmission of the signal from adaptor proteins to the nucleus without mediation by RAS is possible through Fak/Src or Rho/Rac/CDC42 pathways. In addition, phospholipase C-gamma is activated by direct interaction with the phosphorylated c-erb-B-2; however, its intracellular pathway is not fully known. The final result is the induction of transcription factors (ie, Myc, NF-kB, ATF, Ets, AP-1, EIK, SRF) that drive the cell cycle by up-regulating cyclins and inhibiting CDKIs and proapoptotic signals.

Once the biological message has been executed, the complex ligand receptor is internalized and destroyed in the lysosomes. The pattern of heterodimerization, the intracellular pathway used, and the rate of internalization and destruction of the receptor depend on the specific ligand bound to the receptor.

Although c-erb-B2 does not have a specific ligand, its role in the signal transmission from the epidermal growth factor receptor is crucial. Cell lines lacking c-erb-B2 are resistant to the tumorigenic effect of EGF, while those with a kinase-deficient or carboxyl terminal–truncated EGF receptor with intact c-erb-B2 can still execute all the functions of the wild type.

The discovery of the role of HER2 in breast cancer was one of the landmarks in breast cancer research in the last 2 decades. HER2 is overexpressed in 20-30% of breast cancers. Tumor cells overexpressing HER2/neu may have up to 2 million copies of the receptor on their surface compared with 20,000-50,000 copies in normal breast epithelial cells. Because of this abundance of HER2/neu, many heterodimers contain HER2/neu, resulting in potent intracellular signaling and malignant growth.

Despite persistent controversy regarding certain aspects of its biology, prognostic value, and methods of evaluation, HER2 overexpression or amplification is generally accepted to be correlated with a high histologic grade, the absence of hormone receptor expression, aneuploidy, a high proliferation index, tumor size, and a poor clinical outcome. Its role as a predictor of response to chemotherapy and hormonal therapy (HT) is not clearly defined.

Certain clinical studies using tamoxifen showed not only a lack of response, but also a detrimental effect in the group of patients overexpressing HER2. Retrospectively reviewed chemotherapy data showed longer disease-free survival and overall survival in HER2 overexpressors who received high doses of doxorubicin-containing chemotherapy compared with HER2-negative patients. Available data concerning the interaction between cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and HER2 overexpression are inconclusive and do not allow the formation of final conclusions. Taxanes seem to have high efficacy in patients overexpressing HER2 (relative risk, 65%) compared with the HER2-negative group (relative risk, 35%).

The IGF family consists of IGF-1, IGF-2, IGF receptor-1, IGF receptor-2, and IGF-binding proteins. The members of this family play an important role in normal mammary development and tumorigenesis. Both IGF-1 and IGF-2 bind to IGF receptor-1, whose strong mutagenic effect is synergistic with estrogen. In breast cancer, IGF receptor-1 and IGF-1 and IGF-2 are overexpressed in epithelial cells and stromal cells, respectively. Paradoxically, this overexpression correlates with a good prognosis, perhaps reflecting simple hormone dependence or association. IGF receptor-2 plays a tumor-suppressing role by down-regulating IGF-2.

The TGF-beta family consists of 3 TGF-beta and 2 interdependent serine-threonine kinase receptors. In normal mammary epithelial cells, TGF-beta blocks the expression of cyclin A, an S-phase–promoting protein and (to a lesser degree) cyclins D and E involved in the G1 phase and induces the expression of the CDKI p15, which results in cell-cycle arrest and, potentially, apoptosis. This explains its role in postlactational mammary gland regression.

Expression of TGF-beta in breast cancer is increased and seems to correlate with disease progression rather than tumor suppression. Mutation of TGF-beta receptors (type I and II) or any of the downstream molecules (Smad4) involved in intracellular signal transduction renders breast cancer cells resistant to its suppressive effects. However, its role in promoting angiogenesis and invasion and in suppressing the immune system becomes advantageous for the cancer cells, which acquire a proliferative advantage by losing sensitivity to TGF-beta and developing a way to escape the host immunosurveillance.

Mutated BRCA1 and BRCA2, breast cancer susceptibility genes, are proven risk factors for breast cancer. More than 500 mutations have been described in the BRCA1 gene (band 17q21), and 250 have been described in the BRCA2 gene (band 13q12-13). The mutations occurring at either end of the BRCA1 gene are associated with more aggressive tumors; those occurring at the 5` extremity are associated with breast and ovarian cancers, while those closer to the 3` end are associated with only breast cancer.

The biological function of the BRCA1 gene product is not well known. Accumulated evidence suggests that BRCA1 is a nuclear protein involved in other genes' expression, in cell cycle progression, and in the response to DNA damage. DNA damage results in activation and interaction of BRCA1, BRCA2, RAD51, and TP53 with subsequent expression of p21, which leads to a cell cycle pause until the damage is repaired. The mutation or absence of BRCA1 results in failure to repair the damaged DNA, and the cell cycle continues to accumulate further mutations, eventually leading to tumorigenesis. BRCA2 seems to play a role similar to that of BRCA1 in the cell cycle, other genes' expression, and DNA damage repair.

Prevention

The most important risk factors for the development of breast cancer are sex, age, and genetics. Because women can do nothing about these risks, regular screening is recommended in order to allow early detection and thus prevent death from breast cancer.

Regular screening includes breast self-examination, clinical breast examination, and mammography.

Breast self-examination (BSE) is cheap and easy. Routine monthly examination may be helpful. Previously considered critical, more recent studies suggest that self breast exam may be less valuable than previously thought, especially for women who are having routine clinical breast examination and/or mammography.

* For women who are menstruating, the best time for examination is immediately after the monthly period.

* For women who are not menstruating or whose periods are extremely irregular, picking a certain date each month seems to work best.

* Instruction in the technique of breast self-examination can be obtained from your health-care provider or from any one of several organizations interested in breast cancer.

Clinical breast examination: The American Cancer Society recommends a breast examination by a trained health-care provider once every three years starting at age 20 years, and then yearly after age 40 years.

Mammograms are recommended every one to two years starting at age 40 years. For women at high risk for the development of breast cancer, mammogram screening may start earlier, generally 10 years prior to the age at which the youngest close relative developed breast cancer.

Obesity after menopause and excessive alcohol intake may increase the risk of breast cancer slightly. Physically active women may have a lower risk. All women are encouraged to maintain normal body weight, especially after menopause and to limit excess alcohol intake. Hormone replacement should be limited in duration if it is medically required.

In women who are genetically at high risk for the development of breast cancer, tamoxifen has been shown to significantly decrease the incidence of the disease. Side effects should be carefully discussed with your health-care provider prior to embarking on therapy. A second drug, raloxifene (Evista), which is now being used for the treatment of osteoporosis, also blocks the effects of estrogen and appears to prevent breast cancer. Initial studies showed that both tamoxifen and raloxifene were able to reduce the risk of invasive breast cancer, but raloxifene did not have this protective effect against noninvasive cancer. Studies are ongoing to further characterize the effectiveness and indications for use of raloxifene as a breast cancer preventive drug.

Occasionally, a woman at very high risk for development of breast cancer will decide to have a preventive or prophylactic mastectomy to avoid developing breast cancer. Additionally, removal of the ovaries has shown to reduce the risk of developing breast cancer in women who have the BRCA1 mutation and who have their ovaries surgically removed before they reach age 40.

Treatment

The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. In February 2007, the MammaPrint test became the first breast cancer predictor to win formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.

Also see.

Complications

The list of complications that have been mentioned in various sources for Breast Cancer includes:

Complications and sequelae of Breast Cancer include:

* Cachexia
* Cerebral metastases
* Lymphangitis carcinomatosa
* Breast lump
* Opsoclonus
* Lung metastases
* Brachial plexus neuropathy
* Back pain
* Liver metastases
* Bone metastases
* Prostate specific antigen levels raised (plasma or serum)
* Bone pain
* CEA raised
* Renal metastases
* Mastalgia
* Pleural effusion
* Lymphadenopathy
* Leucoerythroblastic anemia
* Cutaneous metastasis
* Osteosclerosis
* Nipple discharge

References

http://www.wikipedia.org
Served as primary source.

http://www.emedicinehealth.com
Served as secondary source.

http://healthlink.mcw.edu
Served as extra reference.

http://www.emedicine.com
Provided information on Pathogenesis/Pathophysiology.

http://www.wrongdiagnosis.com
Provided extra information and reference.

Uterine Fibroid

Compiled and Summarized by Alex
Uterine fibroids are noncancerous growths of the uterus that often appear during childbearing years. Also called fibromyomas, leiomyomas or myomas, uterine fibroids aren't associated with an increased risk of uterine cancer and almost never develop into cancer.

As many as three out of four women have uterine fibroids, but most are unaware of them because they often cause no symptoms. The doctor may discover them incidentally during a pelvic exam or prenatal ultrasound.

In general, uterine fibroids cause no problems and seldom require treatment. Medical therapy and surgical procedures can shrink or remove fibroids if there is no discomfort or troublesome symptoms. Rarely, fibroids can require emergency treatment if they cause sudden, sharp pelvic pain.

Signs and Symptoms

Uterine fibroids are often asymptomatic. Rapidly enlarging tumors may cause pelvic pain. They are a common cause of heavy or irregular menstrual bleeding. In women of child bearing age, these tumors may produce infertility. Excessive blood loss can lead to signs of anemia, including fatigue, shortness of breath, rapid heart rate and pallor.

Causes

Uterine fibroids develop from the smooth muscular tissue of the uterus (myometrium). A single cell reproduces repeatedly, eventually creating a pale, firm, rubbery mass distinct from neighboring tissue.

Fibroids range in size from seedlings, undetectable by the human eye, to bulky masses that can distort and enlarge the uterus. They can be single or multiple, in extreme cases expanding the uterus so much that it reaches the rib cage.

Doctors don't know the cause of uterine fibroids, but research and clinical experience point to several factors:

· Genetic alterations. Many fibroids contain alterations in genes that code for uterine muscle cells.

· Hormones. Estrogen and progesterone, two hormones that stimulate development of the uterine lining in preparation for pregnancy, appear to promote the growth of fibroids. Fibroids contain more estrogen and estrogen receptors than do normal uterine muscle cells.

· Other chemicals. Substances that help the body maintain tissues, such as insulin-like growth factor, may affect fibroid growth.

Diagnosis

Uterine fibroids are frequently found incidentally during a routine pelvic exam. The doctor may feel irregularities in the shape of the uterus through the abdomen, suggesting the presence of fibroids.

Ultrasound

If confirmation is needed, the doctor may obtain an ultrasound — a painless exam that uses sound waves to obtain a picture of the uterus — to confirm the diagnosis and to map and measure fibroids. A doctor or technician moves the ultrasound device (transducer) over the abdomen (transabdominal) or places it inside the vagina (transvaginal) to obtain images of the uterus.

Transvaginal ultrasound provides more detail because the probe is closer to the uterus. Transabdominal ultrasound visualizes a larger anatomic area. Sometimes, fibroids are discovered during an ultrasound conducted for a different purpose, such as during a prenatal ultrasound.

Other imaging tests

If traditional ultrasound doesn't provide enough information, the doctor may order other imaging studies, such as:

· Hysterosonography. This ultrasound variation uses sterile saline to expand the uterine cavity, making it easier to obtain interior images of the uterus. This test may be useful if there is heavy menstrual bleeding despite normal results from traditional ultrasound.

· Hysterosalpingography. This technique uses a dye to highlight the uterine cavity and fallopian tubes on X-ray images. The doctor may recommend it if infertility is a concern. In addition to revealing fibroids, it can help the doctor determine if the fallopian tubes are open.

· Hysteroscopy. The doctor inserts a small, lighted telescope called a hysteroscope through the cervix into the uterus. The tube releases a gas or liquid to expand the uterus, allowing the doctor to examine the walls of the uterus and the openings of the fallopian tubes. A hysteroscopy can be performed in the doctor's office.

Imaging techniques that may occasionally be necessary include computerized tomography (CT) and magnetic resonance imaging (MRI).

Other tests

If the client is experiencing abnormal vaginal bleeding, the doctor may want to conduct other tests to investigate potential causes. He or she may order a complete blood count (CBC) to determine if there is iron deficiency anemia because of chronic blood loss. The doctor may also order blood tests to rule out bleeding disorders and to determine the levels of reproductive hormones produced by the ovaries.

Pathogenesis

For complete detail. See link.

Pathophysiology

Smooth-muscle tumors of uterine origin encompass a broad family of neoplasms. The leiomyoma, by far the most common of all the neoplasms, generally is hormone sensitive, with rates of growth semiquantitatively related to estrogen and progesterone receptor levels. Several forms of degenerative change can occur in the leiomyoma. The most common is hyaline degeneration, which is important in that it should not be mistaken for the coagulative tumor cell necrosis seen in leiomyosarcoma. Red degeneration (necrobiosis) is a form of degeneration that occurs characteristically but not exclusively in pregnancy, and the process is often the cause of pain and fever. Several forms of treatment have been used medically in the treatment of leiomyoma. Gonadotropin-releasing hormone analogs or agonists or selective arterial embolization with polyvinylformaldehyde particles may lead to substantial degeneration or infarction of the leiomyoma, respectively. Several variants of leiomyoma, the cellular and symplastic leiomyomas, are important to recognize, as they can be misinterpreted as sarcoma. In addition, there are two unusual growth patterns of leiomyoma that are important to recognize. Both the benign metastasizing leiomyoma and disseminated peritoneal leiomyomatosis are found outside the uterus, and neither is malignant. Recent studies offer insights into their origin and hormonal influences. From a diagnostic and therapeutic point of view, the leiomyosarcoma, while rare, is clinically of great import. Coagulative necrosis, cytologic atypia, and mitotic counts are all important in diagnosing the condition.

Prevention

Although researchers continue to study the causes of fibroid tumors, little scientific advice is available on how to prevent them. Preventing uterine fibroids may not be possible, but you can take comfort in the fact that only a small percentage of these tumors require treatment.

Treatment

There's no single best approach to uterine fibroid treatment. Many treatment options exist. In most cases, the best action to take after discovering fibroids is simply to be aware they are there.

Watchful waiting

If you're like most women with uterine fibroids, you have no signs or symptoms. In your case, watchful waiting (expectant management) could be the best course. Fibroids aren't cancerous. They rarely interfere with pregnancy. They usually grow slowly and tend to shrink after menopause when levels of reproductive hormones drop. This is the best treatment option for a large majority of women with uterine fibroids.

Medications

Medications for uterine fibroids target hormones that regulate menstrual cycle, treating symptoms such as heavy menstrual bleeding and pelvic pressure. They don't eliminate fibroids, but may shrink them. Medications include:

· Gonadotropin-releasing hormone (Gn-RH) agonists. To trigger a new menstrual cycle, a control center in the brain called the hypothalamus manufactures gonadotropin-releasing hormone (Gn-RH). The substance travels to the pituitary gland, a tiny gland also located at the base of the brain, and sets in motion events that stimulate the ovaries to produce estrogen and progesterone.

Medications called Gn-RH agonists (Lupron, Synarel, others) act at the same sites that Gn-RH does. But when taken as therapy, a Gn-RH agonist produces the opposite effect to that of the natural hormone. Estrogen and progesterone levels fall, menstruation stops, fibroids shrink and anemia often improves.

· Androgens. The ovaries and the adrenal glands, located above your kidneys, produce androgens, the so-called male hormones. Given as medical therapy, androgens can relieve fibroid symptoms.

Danazol, a synthetic drug similar to testosterone, has been shown to shrink fibroid tumors, reduce uterine size, stop menstruation and correct anemia. However, occasional unpleasant side effects such as weight gain, dysphoria (feeling depressed, anxious or uneasy), acne, headaches, unwanted hair growth and a deeper voice, make many women reluctant to take this drug.

· Other medications. Oral contraceptives or progestins can help control menstrual bleeding, but they don't reduce fibroid size. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are not hormonal medications, are effective for heavy vaginal bleeding unrelated to fibroids, but they don't reduce bleeding caused by fibroids.

Hysterectomy

This operation — the removal of the uterus — remains the only proven permanent solution for uterine fibroids. But hysterectomy is major surgery. It ends the ability to bear children, and if elected to have ovaries removed also, it brings on menopause and the question of whether you'll take hormone replacement therapy.

Myomectomy

In this surgical procedure, the surgeon removes the fibroids, leaving the uterus in place. If you want to bear children, you might choose this option. With myomectomy, as opposed to a hysterectomy, there is a risk of fibroid recurrence. There are several ways a myomectomy can be done:

· Abdominal myomectomy. If having multiple fibroids, very large or very deep fibroids, the doctor may use an open abdominal surgical procedure to remove the fibroids.

· Laparoscopic myomectomy. If the fibroids are small and few in number, the client and the doctor may opt for a laparoscopic procedure, which uses slender instruments inserted through small incisions in the abdomen to remove the fibroids from the uterus. The doctor views the abdominal area on a remote monitor via a small camera attached to one of the instruments.

· Hysteroscopic myomectomy. This procedure may be an option if the fibroids are contained inside the uterus (submucosal). A long, slender scope (hysteroscope) is passed through the vagina and cervix and into the uterus. The doctor can see and remove the fibroids through the scope. This procedure is best performed by a doctor experienced in this technique.

Variations of myomectomy — in which uterine fibroids are destroyed without actually removing them — include:

· Myolysis. In this laparoscopic procedure, an electric current destroys the fibroids and shrinks the blood vessels that feed them.

· Cryomyolysis. In a procedure similar to myolysis, cryomyolysis uses liquid nitrogen to freeze the fibroids.

The safety, effectiveness and associated risk of fibroid recurrence of myolysis and cryomyolysis have yet to be determined.

· Endometrial ablation. This treatment, performed with a hysteroscope, uses heat to destroy the lining of the uterus, either ending menstruation or reducing the menstrual flow. Endometrial ablation is effective in stopping abnormal bleeding, but doesn't affect fibroids outside the interior lining of the uterus.

Uterine artery embolization

Small particles injected into the arteries supplying the uterus cut off blood flow to fibroids, causing them to shrink. This technique is proving effective in shrinking fibroids and relieving the symptoms they can cause. Advantages over surgery include:

· No incision
· Shorter recovery time

Complications may occur if the blood supply to the ovaries or other organs is compromised.

Focused ultrasound surgery

MRI-guided focused ultrasound surgery (FUS), approved by the Food and Drug Administration in October 2004, is a newer treatment option for women with fibroids. Unlike other fibroid treatment options, FUS is noninvasive and preserves the uterus.

This procedure is performed while the client is inside of a specially crafted MRI scanner that allows doctors to visualize the anatomy, and then locate and destroy (ablate) fibroids inside the uterus without making an incision. Focused high-frequency, high-energy sound waves are used to target and destroy the fibroids. A single treatment session is done in an on- and off-again fashion, sometimes spanning several hours. Initial results with this technology are promising, but its long-term effectiveness is not yet known.

Notes to consider before deciding

Before making a decision, consider the pros and cons of all available treatment options in relation to your particular situation. Remember, most women don't need any treatment for uterine fibroids.

Complications

Although uterine fibroids usually aren't dangerous, they can cause discomfort and may lead to complications such as anemia from heavy blood loss. In rare instances, fibroid tumors can grow out of the uterus on a stalk-like projection. If the fibroid twists on this stalk, a sudden, sharp, severe pain in the lower abdomen may develop. If so, seeking medical care is strongly recommended. Surgery may be needed.

Pregnancy and fibroids

Because uterine fibroids typically develop during the childbearing years, women with fibroids are often concerned about their chances of a successful pregnancy.

Fibroids usually don't interfere with conception and pregnancy, but they can occasionally affect fertility. They may distort or block the fallopian tubes, or interfere with the passage of sperm from the cervix to the fallopian tubes. Submucosal fibroids may prevent implantation and growth of an embryo.

Research indicates that pregnant women with fibroids are at slightly increased risk of miscarriage, premature labor and delivery, abnormal fetal position, and separation of the placenta from the uterine wall. But not all studies confirm these associations. Furthermore, complications vary based on the number, size and location of fibroids. Multiple fibroids and large submucosal fibroids that distort the uterine cavity are the type most likely to cause problems. A more common complication of fibroids in pregnancy is localized pain, typically between the first and second trimesters. This is usually easily treated with pain relievers.

In most cases, fibroids don't interfere with pregnancy and treatment isn't necessary. It was once believed that fibroids grew faster during pregnancy, but multiple studies suggest otherwise. Most fibroids remain stable in size, although some increase or decrease slightly, usually in the first trimester.

If there are fibroids and the patient experienced repeated pregnancy losses, the doctor may recommend removing one or more fibroids to improve the chances of carrying a baby to term, especially if no other causes of miscarriage can be found and the fibroids distort the shape of the uterine cavity.

Doctors usually don't remove fibroids in conjunction with a Caesarean section because of the high risk of excessive bleeding.

References:

http://www.mayoclinic.com
Served as primary source.

http://www.myelectronicmd.com
Served as reference.

http://www.ehponline.org
Source for Pathophysiology.

If you find an error, please let us know.

Diabetes Mellitus

Compiled and Summarized by Anthony
Diabetes mellitus (IPA: [ˌdaɪəˈbiːtiːz] or [ˌdaɪəˈbiːtəs], [məˈlaɪtəs] or [ˈmɛlətəs]), often simply diabetes (Greek: Διαβήτης), is a syndrome characterized by disordered metabolism and inappropriately high blood sugar (hyperglycemia) resulting from either low levels of the hormone insulin or from abnormal resistance to insulin's effects coupled with inadequate levels of insulin secretion to compensate. The characteristic symptoms are excessive urine production (polyuria), excessive thirst and increased fluid intake (polydipsia), and blurred vision; these symptoms are likely absent if the blood sugar is only mildly elevated.

The World Health Organization recognizes three main forms of diabetes mellitus: type 1, type 2, and gestational diabetes (occurring during pregnancy), which have similar signs, symptoms, and consequences, but different causes and population distributions. While, ultimately, all forms are due to the beta cells of the pancreas being unable to produce sufficient insulin to prevent hyperglycemia, the causes are different. Type 1 diabetes is usually due to autoimmune destruction of the pancreatic beta cells, which produce insulin. Type 2 diabetes is characterized by insulin resistance in target tissues, this causes a need for abnormally high amounts of insulin and diabetes develops when the beta cells cannot meet this demand. Gestational diabetes is similar to type 2 diabetes in that it involves insulin resistance; the hormones of pregnancy can cause insulin resistance in women genetically predisposed to developing this condition.

Gestational diabetes typically resolves with delivery of the child, however types 1 and 2 diabetes are chronic conditions. All types have been treatable since insulin became medically available in 1921. Type 1 diabetes, in which insulin is not secreted by the pancreas, is directly treatable only with injected or inhaled insulin, although dietary and other lifestyle adjustments are part of management. Type 2 may be managed with a combination of dietary treatment, tablets and injections and, frequently, insulin supplementation. While insulin was originally produced from natural sources such as porcine pancreas, most insulin used today is produced through genetic engineering, either as a direct copy of human insulin, or human insulin with modified molecules that provide different onset and duration of action. Insulin can also be delivered continuously by a specialized pump which subcutaneously provides insulin through a changeable catheter.

Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease (doubled risk), chronic renal failure, retinal damage (which can lead to blindness), nerve damage (of several kinds), and microvascular damage, which may cause impotence and poor healing. Poor healing of wounds, particularly of the feet, can lead to gangrene, which may require amputation. Adequate treatment of diabetes, as well as increased emphasis on blood pressure control and lifestyle factors (such as not smoking and keeping a healthy body weight), may improve the risk profile of most aforementioned complications. In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly, the leading cause of non-traumatic amputation in adults, and diabetic nephropathy is the main illness requiring renal dialysis.

Signs and Symptoms

The classical triad of diabetes symptoms is polyuria, polydipsia and polyphagia, which are, respectively, frequent urination; increased thirst and consequent increased fluid intake; and increased appetite. Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children. However, in type 2 diabetes the symptoms develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause weight loss (despite normal or increased eating) and irreducible fatigue. These symptoms can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled.

When the glucose concentration in the blood is raised beyond the renal threshold, reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits the reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells, causing dehydration and increased thirst.

Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes. Blurred vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected in cases of rapid vision change whereas type 2 is generally more gradual, but should still be suspected.

Patients (usually with type 1 diabetes) may also present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by the smell of acetone on the patient's breath; a rapid, deep breathing known as Kussmaul breathing; polyuria; nausea; vomiting and abdominal pain; and any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy). In severe DKA, coma may follow, progressing to death. Diabetic ketoacidosis is a medical emergency and requires hospital admission.

A rarer but equally severe possibility is hyperosmolar nonketotic state, which is more common in type 2 diabetes and is mainly the result of dehydration due to loss of body water. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a vicious circle in regard to the water loss.

Cause

Drugs such as steroids, Dilantin, and others may elevate the blood sugar through a variety of mechanisms. Certain other drugs, such as alloxan, streptozocin, and thiazide diuretics, are toxic to the beta cells of the pancreas and can cause diabetes. Certain syndromes (for example, Prader-Willi, Down's, Progeria, and Turner's) may result in a hyperglycemic state; if this state is prolonged, the result can be permanent diabetes.

Diabetes resulting in an insulin-dependent state is classified as Type 1 diabetes. While Type 1 diabetes affects only between 5 to10 percent of the diabetic population, its effects on the body can be worse than other forms of diabetes. In the past, Type 1 has been known as juvenile or juvenile-onset diabetes (because it is usually diagnosed in those under thirty), brittle diabetes, unstable diabetes, and ketosis-prone diabetes. People in this classification more frequently exhibit the classic symptoms, usually with ketones present in blood and urine. A blood-sugar level of 800 mg/dl (44 mmol) or more, especially if ketones are not present, indicates a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (a state in which the body is extremely dry (dehydrated), the chemicals in the body are concentrated, and the blood sugar is high).

As stated before, diabetes is a syndrome or group of diseases (rather than one disease), leading to the prolonged hyperglycemic state. Type 1 is most associated with the killing of the beta cells, most likely by the body's own immune system. Either the immune system cannot kill an infecting agent, which then kills the beta cells, or the immune system itself goes "wild," attacking the body's own tissue and destroying the beta cells. The cells of the islets of Langerhans are inflamed, resulting from an infectious-disease process (for example, mumps) or, more commonly, from an autoimmune (allergic to self) response.

The autoimmune process results in the circulation of antibodies that may either cause or be caused by beta-cell death. If it is found that the antibodies cause beta-cell destruction (the body fighting what it now considers foreign to itself), the body's response to the Type 1 diabetes is much less severe (i.e., easier to control) with treatment. Until then, the outcome is a lack of available insulin. While the onset is said to be sudden, changes resulting in decreased insulin availability may have occurred over a longer period of time. In short, insulin-dependent diabetes mellitus is an inherited defect of the body's immune system, resulting in destruction of the insulin-producing beta cells of the pancreas.

Heredity is a major cause of diabetes. If both parents have Type 2 diabetes, there is a chance that nearly all of their children will have diabetes. If both parents have Type 1 diabetes, fewer than 20 percent of their children will develop Type 1 diabetes. In identical twins, if one twin develops Type 2 diabetes, the chance is nearly 100 percent that the other twin will also develop it. In Type 1 diabetes, however, only 40 to 50 percent of the second twins will develop the disease, indicating that while inheritance is important, environmental factors (for example, too much food, too much stress, viral infection, and so forth) are also involved in the development of Type 1 diabetes.

Diagnosis

The diagnosis of type 1 diabetes, and many cases of type 2, is usually prompted by recent-onset symptoms of excessive urination (polyuria) and excessive thirst (polydipsia), often accompanied by weight loss. These symptoms typically worsen over days to weeks; about a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening; detection of hyperglycemia during other medical investigations; and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that is frequently caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:

· fasting plasma glucose level at or above 126 mg/dL (7.0 mmol/l).
· plasma glucose at or above 200 mg/dL (11.1 mmol/l) two hours after a 75 g oral glucose load as in a glucose tolerance test.
· random plasma glucose at or above 200 mg/dL (11.1 mmol/l).

A positive result, in the absence of clinical symptoms of diabetes, should be confirmed by another of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete. According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/l) is considered diagnostic for diabetes mellitus.

Patients with fasting glucose levels between 110 and 125 mg/dL (6.1 and 7.0 mmol/l) are considered to have impaired fasting glycemia. Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/l two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus as well as cardiovascular disease.

While not used for diagnosis, an elevated level of glucose irreversibly bound to hemoglobin (termed glycosylated hemoglobin or HbA1c) of 6.0% or higher (the 2003 revised U.S. standard) is considered abnormal by most labs; HbA1c is primarily used as a treatment-tracking test reflecting average blood glucose levels over the preceding 90 days (approximately). However, some physicians may order this test at the time of diagnosis to track changes over time. The current recommended goal for HbA1c in patients with diabetes is <7.0%, which is considered good glycemic control, although some guidelines are stricter (<6.5%). People with diabetes who have HbA1c levels within this range have a significantly lower incidence of complications from diabetes, including retinopathy and diabetic nephropathy.

Pathogenesis

For IDDM or Type I DM, see link.
For NIDDM or Type 2 DM, see link.

Pathophysiology

Insulin is the principal hormone that regulates uptake of glucose from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.

Much of the carbohydrate in food is converted within a few hours to the monosaccharide glucose, the principal carbohydrate found in blood and used by the body as fuel. Some carbohydrates are not so converted. Notable examples include fruit sugar (fructose), usable as cellular fuel but it is not converted to glucose, and which therefore does not participate in the insulin/glucose metabolic regulatory mechanism. Additionally, the carbohydrate cellulose (though it is actually many glucose molecules in long chains) is not converted to glucose, as humans and many animals have no digestive pathway capable of breaking up cellulose.

Insulin is released into the blood by beta cells (β-cells), found in the Islets of Langerhans in the pancreas, in response to rising levels of blood glucose after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Insulin is also the principal control signal for conversion of glucose to glycogen for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone glucagon which acts in an opposite manner to insulin. Glucose thus recovered by the liver re-enters the bloodstream; muscle cells lack the necessary export mechanism.

Higher insulin levels increase many anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat burning metabolic phase).

If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, then glucose will not be absorbed properly by those body cells that require it nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.

Prevention

Type 1 diabetes risk is known to depend upon a genetic predisposition based on HLA types (particularly types DR3 and DR4), an unknown environmental trigger (suspected to an infection in most cases), and an uncontrolled autoimmune response that attacks the insulin producing beta cells. Some research has suggested that breastfeeding decreased the risk; various other nutritional risk factors are being studied, but no firm evidence has been found.

Type 2 diabetes risk can be reduced in many cases by making changes in diet and increasing physical activity. The American Diabetes Association (ADA) recommends maintaining a healthy weight, getting at least 2½ hours of exercise per week (a brisk sustained walk appears sufficient), having a modest fat intake, and eating a good amount of fiber and whole grains. The ADA does not recommend alcohol consumption as a preventative, but it is interesting to note that moderate alcohol intake may reduce the risk (though heavy consumption clearly increases damage to body systems significantly). There is inadequate evidence that eating foods of low glycemic index is clinically helpful.

Some studies have shown delayed progression to diabetes in predisposed patients through prophylactic use of metformin, rosiglitazone, or valsartan. In patients on hydroxychloroquine for rheumatoid arthritis, incidence of diabetes was reduced by 77%. Breastfeeding might also be correlated with the prevention of type 2 of the disease in mothers.

Treatment

Diabetes mellitus is currently a chronic disease, without a cure, and medical emphasis must necessarily be on managing/avoiding possible short-term as well as long-term diabetes-related problems. There is an exceptionally important role for patient education, dietetic support, sensible exercise, self glucose monitoring, with the goal of keeping both short-term blood glucose levels, and long term levels as well, within acceptable bounds. Careful control is needed to reduce the risk of long term complications. This can be achieved with combinations of diet, exercise and weight loss (type 2), various oral diabetic drugs (type 2 only), and insulin use (type 1 and increasingly for type 2 not responding to oral medication). In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications should be undertaken to control blood pressure and cholesterol by exercising more, smoking cessation, consuming an appropriate diet, wearing diabetic socks, and if necessary, taking any of several drugs to reduce pressure.

In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care of a patient in a team approach. Optometrists, podiatrists/chiropodists, dietitians, physiotherapists, clinical nurse specialists (eg, Certified Diabetes Educators and DSNs (Diabetic Specialist Nurse)), or nurse practitioners may jointly provide multidisciplinary expertise. In countries where patients must provide their own health care, the impact of out-of-pocket costs of diabetic care can be high. In addition to the medications and supplies needed, patients are often advised to receive regular consultation from a physician (eg, at least every three to six months).

Complications

People with diabetes may experience many serious, long-term complications. Some of these complications begin within months of the onset of diabetes, although most tend to develop after a few years. Most of the complications are progressive. The more tightly a person with diabetes is able to control the levels of sugar in the blood, the less likely it is that these complications will develop or become worse.

High sugar levels cause narrowing of both the small and large blood vessels. Complex sugar-based substances build up in the walls of small blood vessels, causing them to thicken and leak. As they thicken, they supply less blood, especially to the skin and nerves. Poor control of blood sugar levels also tends to cause the levels of fatty substances in the blood to rise, resulting in atherosclerosis and decreased blood flow in the larger blood vessels. Atherosclerosis is between 2 and 6 times more common in people with diabetes than in people who do not have the disease and tends to occur at younger ages.

Over time, elevated levels of sugar in the blood and poor circulation can harm the heart, brain, legs, eyes, kidneys, nerves, and skin, resulting in angina, heart failure, strokes, leg cramps on walking (claudication), poor vision, renal failure, damage to nerves (neuropathy), and skin breakdown. Heart attacks and strokes are more common among people with diabetes.

Poor circulation to the skin can lead to ulcers and infections, and all wounds heal slowly. People with diabetes are particularly likely to have ulcers and infections of the feet and legs. Too often, these wounds heal slowly or not at all, and amputation of the foot or part of the leg may be needed.

People with diabetes often develop bacterial and fungal infections, typically of the skin. When the levels of sugar in the blood are high, white blood cells cannot effectively fight infections. Any infection that develops tends to be more severe.

Damage to the blood vessels of the eye can cause loss of vision (diabetic retinopathy. Laser surgery can seal the leaking blood vessels of the eye and prevent permanent damage to the retina. Therefore, people with diabetes should have yearly eye examinations to check for damage.

The kidneys can malfunction, resulting in kidney failure that may require dialysis or kidney transplantation. Doctors usually check the urine of people with diabetes for abnormally high levels of protein (albumin), which is an early sign of kidney damage. At the earliest sign of kidney complications, the person is often given angiotensin-converting enzyme (ACE) inhibitors, drugs that slow the progression of kidney disease.

Damage to nerves can manifest in several ways. If a single nerve malfunctions, an arm or leg may suddenly become weak. If the nerves to the hands, legs, and feet become damaged (diabetic polyneuropathy), sensation may become abnormal, and tingling or burning pain and weakness in the arms and legs may develop. Damage to the nerves of the skin makes repeated injuries more likely because the person cannot sense changes in pressure or temperature.

References

http://www.wikipedia.org
Served as primary source.

http://www.merck.com
Served as secondary source and reference.

http://www.gpnotebook.co.uk
Provided information on Pathogenesis.

http://nursing-resource.com/

If you find an error, please let us know.