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Monday, February 3, 2020

CANCER




      
      
    Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.


    The major types of cancer are carcinoma, sarcoma, melanoma, lymphoma, and leukemia. Carcinomas -- the most commonly diagnosed cancers -- originate in the skin, lungs, breasts, pancreas, and other organs and glands. Lymphomas are cancers of lymphocytes. Leukemia is cancer of the blood. It does not usually form solid tumors. Sarcomas arise in bone, muscle, fat, bloodvessels, cartilage, or other soft or connective tissues of the body. They are relatively uncommon. Melanomas are cancers that arise in the cells that make the pigment in skin.


    Cancer has been recognized for thousands of years as a human ailment, yet only in the past century has medical science understood what cancer really is and how it progresses. Cancer specialists, called oncologists, have made remarkable advances in cancer diagnosis, prevention, and treatment. Today, more people diagnosed with cancer are living longer. However, some forms of the disease remain frustratingly difficult to treat. Modern treatment can significantly improve quality of life and may extend survival.


Signs and symptoms

When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancer's type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer can be difficult to diagnose and can be considered a "great imitator.


Local symptoms

Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that can lead to symptoms such as coughing up blood (lung cancer), anemia or rectal bleeding (colon cancer), blood in the urine (bladder cancer), or abnormal vaginal bleeding (endometrial or cervical cancer). Although localized pain may occur in advanced cancer, the initial tumor is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.


Systemic symptoms

Systemic symptoms may occur due to the body's response to the cancer. This may include fatigue, unintentional weight loss, or skin changes. Some cancers can cause a systemic inflammatory state that leads to ongoing muscle loss and weakness, known as cachexia.


Some types of cancer such as Hodgkin disease, leukemias and cancers of the liver or kidney can cause a persistent fever.


Some systemic symptoms of cancer are caused by hormones or other molecules produced by the tumor, known as paraneoplastic syndromes. Common paraneoplastic syndromes include hypercalcemia which can cause altered mental state, constipation and dehydration, or hyponatremia that can also cause altered mental status, vomiting, headache or seizures.



METASTASIS


Cancer can spread from its original site by local spread, lymphatic spread to regional lymph nodes or by hematogenous spread via the blood to distant sites, known as metastasis. When cancer spreads through the blood, it may spread through the body but is more likely to travel to certain areas depending on the cancer type. The symptoms of metastatic cancers depend on the tumor location and can include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard), enlarged liver or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.


CAUSES


The majority of cancers, some 90–95% of cases, are due to genetic mutations from environmental and lifestyle factors. The remaining 5–10% are due to inherited genetics. Environmental refers to any cause that is not inherited genetically, such as lifestyle, economic, and behavioral factors and not merely pollution. Common environmental factors that contribute to cancer death include tobacco (25–30%), diet and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), lack of physical activity, and pollution. Psychological stress does not appear to be a risk factor for the onset of cancer, though it may worsen outcomes in those who already have cancer.


It is not generally possible to prove what caused a particular cancer because the various causes do not have specific fingerprints. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional organ donors, cancer is generally not a transmissible disease.


CHEMICALS

Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.


Tobacco smoke, for example, causes 90% of lung cancer. It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.


Tobacco is responsible for about one in five cancer deaths worldwide and about one in three in the developed world. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.


In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers. Cancer from work-related substance exposures may cause between 2 and 20% of cases, causing at least 200,000 deaths. Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.


DIET AND EXERCISE

Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths. In the United States, excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths. A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system. More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.


Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer. Aflatoxin B1, a frequent food contaminant, causes liver cancer. Betel nut chewing can cause oral cancer. National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet while colon cancer is more common in the United States. Immigrant cancer profiles mirror those of their new country, often within one generation.


INFECTION

Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion ranges from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.


Oncoviruses (viruses that can cause cancer) include human papillomavirus (cervical cancer), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma. Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).

RADIATION
Radiation exposure such as ultraviolet radiation and radioactive material is a risk factor for cancer. Many non-melanoma skin cancers are due to ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.

Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.

Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.


Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources has been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer. Evidence, however, has not supported a concern. This includes that studies have not found a consistent link between mobile phone radiation and cancer risk.

HEREDITY
The vast majority of cancers are non-hereditary (sporadic). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer. Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer, among others.

Statistically for cancers causing most mortality, the relative risk of developing colorectal cancer when a first-degree relative (parent, sibling or child) has been diagnosed with it is about 2. The corresponding relative risk is 1.5 for lung cancer, and 1.9 for prostate cancer. For breast cancer, the relative risk is 1.8 with a first-degree relative having developed it at 50 years of age or older, and 3.3 when the relative developed it when being younger than 50 years of age.

Taller people have an increased risk of cancer because they have more cells than shorter people. Since height is genetically determined to a large extent, taller people have a heritable increase of cancer risk.


PHYSICAL AGENTS
Some substances cause cancer primarily through their physical, rather than chemical, effects. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs.  Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are believed to have similar effects.  Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite and tridymite). Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.

Physical trauma resulting in cancer is relatively rare.  Claims that breaking bones resulted in bone cancer, for example, have not been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer. One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. Frequent consumption of scalding hot tea may produce esophageal cancer. Generally, it is believed that cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma. However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.

Chronic inflammation has been hypothesized to directly cause mutation. Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment. Oncogenes build up an inflammatory pro-tumorigenic microenvironment.

HORMONES
Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.

Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry and have a correspondingly higher level of prostate cancer. Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.

Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones. On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer. Osteosarcoma may be promoted by growth hormones.  Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.

Autoimmune diseases

There is an association between celiac disease and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies.[79] Rates of gastrointestinal cancers are increased in people with Crohn's disease and ulcerative colitis, due to chronic inflammation. Also, immunomodulators and biologic agents used to treat these diseases may promote developing extra-intestinal malignancies.





DIAGNOSIS

Radiation exposure such as ultraviolet radiation and radioactive material is a risk factor for cancer. Many non-melanoma skin cancers are due to ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.

Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.

Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.


Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources has been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer. Evidence, however, has not supported a concern. This includes that studies have not found a consistent link between mobile phone radiation and cancer risk.

Chemotherapy medications


Albumin-bound or nab-paclitaxel  -   Abraxane

Adriamycin - doxorubicin

Carboplatin     : Paraplatin

Cyclophosphamide  :  Cytoxan

Daunorubicin        : Cerubidine, DaunoXome

Doxorubicin      : DOXIL

Epirubicin   :   Ellence

Fluorouracil also called 5-fluorouracil or 5-FU  -- Adrucil

Gemcitabine     --Gemzar

Eribulin)

Ixabepilone)

Methotrexate

Mutamycin

Mitoxantrone     : Novantrone

Vinorelbine   --Navelbine

Taclitaxel  ----Taxol

Docetaxel    --  Taxotere

Thiotepa

Vincristine

Capecitabine




Sunday, February 2, 2020

CORONA VIRUS










            A new coronavirus, designated 2019-nCoV, was identified in Wuhan, the capital of China's Hubei province, after people developed pneumonia without a clear cause and for which existing treatments were not effective. The virus has shown evidence of human-to-human transmission, with its transmission rate escalating in mid-January 2020 and several countries across Europe, North America and especially the Asia-Pacific reporting cases. Its incubation period is between 2 to 14 days, but there is evidence that it may still be contagious during this period and possibly for several days after recovery. Symptoms include fever, coughing and breathing difficulties, and it can be fatal.

   As of 2 February 2020, approximately 14,569 cases have been confirmed, including in every province-level division of China. The first confirmed death occurred on 9 January and since then 305 deaths have been confirmed. A larger number of people may have been infected, but not detected (especially mild cases). The first local transmission of the virus outside China occurred in Vietnam from a father to his son, whereas the first local transmission not involving family occurred in Germany, on 22 January, when a German man contracted the disease from a Chinese business visitor at a meeting near Munich. The first death outside China was reported in the Philippines, when a 44-year old man confirmed to have contracted the virus passed away on 1 February.

     In response, cities with a combined population over 57 million people, comprised of Wuhan and 15 others cities in the surrounding Hubei province, were placed on full or partial lockdown, involving the termination of all urban public transport and outward transport by train, air and long-distance buses. Many New Year events and tourist attractions have been closed to prevent mass gatherings, including the Forbidden City in Beijing and traditional temple fairs. Hong Kong also raised its infectious disease response level to the highest level and declared an emergency, closing its schools until March and cancelling its New Year celebrations.

    A number of countries have issued warnings against travel to Wuhan and Hubei province.Travelers who have visited Mainland China have been asked to monitor their health for at least two weeks and contact their healthcare provider to report any symptoms of the virus. Anyone who suspects that they are carrying the virus are advised to wear a protective mask and seek medical advice by ringing a doctor rather than directly visiting a clinic in person. The travel sector has been providing refunds and no-fee cancellations for reservations in China or by people from China. Airports and train stations have implemented temperature checks, health declarations and information signage in an attempt to identify carriers of the virus.


PREVENTION

There is currently no vaccine to prevent 2019-nCoV infection. The best way to prevent infection is to avoid being exposed to this virus. However, as a reminder, CDC always recommends everyday preventive actions to help prevent the spread of respiratory viruses, including:

    Wash your hands often with soap and water for at least 20 seconds. Use an alcohol-based hand sanitizer that contains at least 60% alcohol if soap and water are not available.
    Avoid touching your eyes, nose, and mouth with unwashed hands.
    Avoid close contact with people who are sick.
    Stay home when you are sick.
    Cover your cough or sneeze with a tissue, then throw the tissue in the trash.
    Clean and disinfect frequently touched objects and surfaces.

These are everyday habits that can help prevent the spread of several viruses. CDC does have






TREATMENT

There is no specific antiviral treatment recommended for 2019-nCoV infection. People infected with 2019-nCoV should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions.
People who think they may have been exposed to 2019-nCoV should contact your healthcare provider immediately.

Sunday, December 15, 2019

Duloxetine



C18H19NOS





Duloxetine, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, and neuropathic pain. It is taken by mouth.


PHARMACOLOGY


Duloxetine inhibits the reuptake of serotonin and norepinephrine (NE) in the central nervous system. Duloxetine increases dopamine (DA) specifically in the prefrontal cortex, where there are few DA reuptake pumps, via the inhibition of NE reuptake pumps (NET), which is believed to mediate reuptake of DA and NE. Duloxetine has no significant affinity for dopaminergic, cholinergic, histaminergic, opioid, glutamate, and GABA reuptake transporters, however, and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NE transporters. Duloxetine undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity.

Major depressive disorder is believed to be due in part to an increase in pro-inflammatory cytokines within the central nervous system. Antidepressants including ones with a similar mechanism of action as duloxetine, i.e. serotonin metabolism inhibition, cause a decrease in proinflammatory cytokine activity and an increase in anti-inflammatory cytokines; this mechanism may apply to duloxetine in its effect on depression but research on cytokines specific to duloxetine therapy is lacking.


The analgesic properties of duloxetine in the treatment of diabetic neuropathy and central pain syndromes such as fibromyalgia are believed to be due to sodium ion channel blockade.

Absorption: Duloxetine is acid labile, and is formulated with enteric coating to prevent degradation in the stomach. Duloxetine has good oral bioavailability, averaging 50% after one 60 mg dose. There is an average 2-hour lag until absorption begins with maximum plasma concentrations occurring about 6 hours post dose. Food does not affect the Cmax of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours.

Distribution: Duloxetine is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein. Volume of distribution is 1640L.

Metabolism: Duloxetine undergoes predominately hepatic metabolism via two cytochrome P450 isozymes, CYP2D6 and CYP1A2. Circulating metabolites are pharmacologically inactive.


Elimination: Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state is usually achieved after 3 days. Only trace amounts (<1%) of unchanged duloxetine are present in the urine and most of the dose (approx. 70%) appears in the urine as metabolites of duloxetine with about 20% excreted in the feces.





Common side effects include dry mouth, nausea, feeling tired, dizziness, agitation, sexual problems, and increased sweating. Severe side effects include an increased risk of suicide, serotonin syndrome, mania, and liver problems. Antidepressant withdrawal syndrome may occur if stopped. There are concerns that use during the later part of pregnancy can harm the baby. It is a serotonin–norepinephrine reuptake inhibitor. How it works is not entirely clear.
Duloxetine was approved for medical use in the United States in 2004. It is available as a generic medication.