<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Dental abscess and can you explain it in depth? [/INST] A dental abscess is a localized collection of pus associated with a tooth. The most common type of dental abscess is a periapical abscess, and the second most common is a periodontal abscess. In a periapical abscess, usually the origin is a bacterial infection that has accumulated in the soft, often dead, pulp of the tooth. This can be caused by tooth decay, broken teeth or extensive periodontal disease (or combinations of these factors). A failed root canal treatment may also create a similar abscess.
A dental abscess is a type of odontogenic infection, although commonly the latter term is applied to an infection which has spread outside the local region around the causative tooth.

Classification
The main types of dental abscess are:

Periapical abscess: The result of a chronic, localized infection located at the tip, or apex, of the root of a tooth.
Periodontal abscess: begins in a periodontal pocket (see: periodontal abscess)
Gingival abscess: involving only the gum tissue, without affecting either the tooth or the periodontal ligament (see: periodontal abscess)
Pericoronal abscess: involving the soft tissues surrounding the crown of a tooth (see: Pericoronitis)
Combined periodontic-endodontic abscess: a situation in which a periapical abscess and a periodontal abscess have combined (see: Combined periodontic-endodontic lesions).

Signs and symptoms
The pain is continuous and may be described as extreme, growing, sharp, shooting, or throbbing. Putting pressure or warmth on the tooth may induce extreme pain. The area may be sensitive to touch and possibly swollen as well.  This swelling may be present at either the base of the tooth, the gum, and/or the cheek, and sometimes can be reduced by applying ice packs.
An acute abscess may be painless but still have a swelling present on the gum. It is important to get anything that presents like this checked by a dental professional as it may become chronic later.
In some cases, a tooth abscess may perforate bone and start draining into the surrounding tissues creating local facial swelling. In some cases, the lymph glands in the neck will become swollen and tender in response to the infection. It may even feel like a migraine as the pain can transfer from the infected area. The pain does not normally transfer across the face, only upwards or downwards as the nerves that serve each side of the face are separate.
Severe aching and discomfort on the side of the face where the tooth is infected is also fairly common, with the tooth itself becoming unbearable to touch due to extreme amounts of pain.

Complications
If left untreated, a severe tooth abscess may become large enough to perforate bone and extend into the soft tissue eventually becoming osteomyelitis and cellulitis respectively. From there it follows the path of least resistance and may spread either internally or externally. The path of the infection is influenced by such things as the location of the infected tooth and the thickness of the bone, muscle and fascia attachments.
External drainage may begin as a boil which bursts allowing pus drainage from the abscess, intraorally (usually through the gum) or extraorally </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Angular cheilitis and can you explain it in depth? [/INST] Angular cheilitis (AC) is inflammation of one or both corners of the mouth. Often the corners are red with skin breakdown and crusting. It can also be itchy or painful. The condition can last for days to years. Angular cheilitis is a type of cheilitis (inflammation of the lips).Angular cheilitis can be caused by infection, irritation, or allergies. Infections include by fungi such as Candida albicans and bacteria  such as Staph. aureus. Irritants include poorly fitting dentures, licking the lips or drooling, mouth breathing resulting in a dry mouth, sun exposure, overclosure of the mouth, smoking, and minor trauma. Allergies may include substances like toothpaste, makeup, and food. Often a number of factors are involved. Other factors may include poor nutrition or poor immune function. Diagnosis may be helped by testing for infections and patch testing for allergies.Treatment for angular cheilitis is typically based on the underlying causes along with the use of a barrier cream. Frequently an antifungal and antibacterial cream is also tried. Angular cheilitis is a fairly common problem, with estimates that it affects 0.7% of the population. It occurs most often in people in their 30s to 60s, and is also relatively common in children. In the developing world, iron, vitamin B12, and other vitamin deficiencies are a common cause.

Signs and symptoms
Angular cheilitis is a fairly non specific term which describes the presence of an inflammatory lesion in a particular anatomic site (i.e. the corner of the mouth). As there are different possible causes and contributing factors from one person to the next, the appearance of the lesion is somewhat variable. The lesions are more commonly symmetrically present on both sides of the mouth, but sometimes only one side may be affected. In some cases, the lesion may be confined to the mucosa of the lips, and in other cases the lesion may extend past the vermilion border (the edge where the lining on the lips becomes the skin on the face) onto the facial skin. Initially, the corners of the mouth develop a gray-white thickening and adjacent erythema (redness). Later, the usual appearance is a roughly triangular area of erythema, edema (swelling) and breakdown of skin at either corner of the mouth. The mucosa of the lip may become fissured (cracked), crusted, ulcerated or atrophied. There is not usually any bleeding. Where the skin is involved, there may be radiating rhagades (linear fissures) from the corner of the mouth. Infrequently, the dermatitis (which may resemble eczema) can extend from the corner of the mouth to the skin of the cheek or chin. If Staphylococcus aureus is involved, the lesion may show golden yellow crusts. In chronic angular cheilitis, there may be suppuration (pus formation), exfoliation (scaling) and formation of granulation tissue.Sometimes contributing factors can be readily seen, such as loss of lower face height from poorly made or worn dentures, which results in mandibular overclosure ("collapse of jaws"). If there is a nutritional deficiency underlying the condition, various other signs and symptoms such as glossitis (swollen tongue) may be present. In people with angular cheilitis who wear dentures, often there may be erythematous mucosa underneath the denture (normally the upper denture), an appearance consistent with denture-related stomatitis. Typically the lesions give symptoms of soreness, pain, pruritus (itching) or burning or a raw feeling.

Causes
Angular cheilitis is thought to be multifactorial disorder of infectious origin, with many local and systemic predisposing factors. The sores in angular cheilitis are often infected with fungi (yeasts), bacteria, or a combination thereof; this may represent a secondary, opportunistic infection by these pathogens. Some studies have linked the initial onset of angular cheilitis with nutritional deficiencies, especially of the B (B2-riboflavin) vitamin and iron (which causes iron deficiency anemia), which in turn may be evidence of malnutrition or malabsorption. Angular cheilitis can be a manifestation of contact dermatitis, which is considered in two groups; irritational and allergic.

Infection
The involved organisms are:

Candida species alone (usually Candida albicans), which accounts for about 20% of cases,
Bacterial species, either:
Staphylococcus aureus alone, which accounts for about 20% of cases,
β-hemolytic streptococci alone. These types of bacteria have been detected in between 8–15% of cases of angular cheilitis, but less commonly are they present in isolation,
Or a combination of the above organisms, (a polymicrobial infection) with about 60% of cases involving both C. albicans and S. aureus.Candida can be detected in 93% of angular cheilitis lesions. This organism is found in the mouths of  about 40% of healthy individuals, and it is considered by some to be normal commensal component of the oral microbiota. However, Candida shows dimorphism, namely a yeast form which is thought to be relatively harmless and a pathogenic hyphal form which is associated with invasion of host tissues. Potassium hydroxide preparation is recommended by some to help distinguish between the harmless and the pathogenic forms, and thereby highlight which cases of angular cheilitis are truly caused by Candida. The mouth may act as a reservoir of Candida that reinfects the sores at the corners of the mouth and prevents the sores from healing.
A lesion caused by recurrence of a latent herpes simplex infection can occur in the corner of the mouth. This is herpes labialis (a cold sore), and is sometimes termed "angular herpes simplex". A cold sore at the corner of the mouth behaves similarly to elsewhere on the lips, and follows a pattern of vesicle (blister) formation followed by rupture leaving a crusted sore which resolves in about 7–10 days, and recurs in the same spot periodically, especially during periods of stress. Rather than utilizing antifungal creams, angular herpes simplex is treated in the same way as a cold sore, with topical antiviral drugs such as aciclovir.

Irritation contact dermatitis
22% of cases of angular cheilitis are due to irritants. Saliva contains digestive enzymes, which may have a degree of digestive action on tissues if they are left in contact. The corner of the mouth is normally exposed to saliva more than any other part of the lips. Reduced lower facial height (vertical dimension or facial support) is usually caused by edentulism (tooth loss), or wearing worn down, old dentures or ones which are not designed optimally. This results in overclosure of the mandible (collapse of the jaws), which extenuates the angular
skin folds at the corners of the mouth, in effect creating an intertriginous skin crease. The tendency of saliva to pool in these areas is increased, constantly wetting the area, which may cause tissue maceration and favors the development of a yeast infection. As such, angular cheilitis is more commonly seen in edentulous people (people without any teeth). It is by contrast uncommon in persons who retain their natural teeth.  Angular cheilitis is also commonly seen in denture wearers. Angular cheilitis is present in about 30% of people with denture-related stomatitis. It is thought that reduced vertical dimension of the lower face may be a contributing factor in up to 11% of elderly persons with angular cheilitis and in up to 18% of denture wearers who have angular cheilitis. Reduced vertical dimension can also be caused by tooth migration, wearing orthodontic appliances, and elastic tissue damage caused by ultraviolet light exposure and smoking.Habits or conditions that keep the corners of the mouth moist might include chronic lip licking, thumb sucking (or sucking on other objects such as pens, pipes, lollipops), dental cleaning (e.g. flossing), chewing gum, hypersalivation, drooling and mouth breathing. Some consider habitual lip licking or picking to be a form of nervous tic, and do not consider this to be true angular cheilitis, instead calling it perlèche (derived from the French word pourlècher meaning "to lick ones lips"), or "factitious cheilitis" is applied to this habit. The term "cheilocandidiasis" describes exfoliative (flaking) lesions of the lips and the skin around the lips, and is caused by a superficial candidal infection due to chronic lip licking. Less severe cases occur during cold, dry weather, and is a form of chapped lips. Individuals may lick their lips in an attempt to provide a temporary moment of relief, only serving to worsen the condition.The sunscreen in some types of lip balm degrades over time into an irritant. Using expired lipbalm can initiate mild angular cheilitis, and when the person applies more lipbalm to alleviate the cracking, it only aggravates it. Because of the delayed onset of contact dermatitis and the recovery period lasting days to weeks, people typically do not make the connection between the causative agent and the symptoms.

Nutritional deficiencies
Several different nutritional deficiency states of vitamins or minerals have been linked to AC. It is thought that in about 25% of people with AC, iron deficiency or deficiency of B vitamins are involved. Nutritional deficiencies may be a more common cause of AC in Third World countries. Chronic iron deficiency may also cause koilonychia (spoon shaped deformity of the fingernails) and glossitis (inflammation of the tongue). It is not completely understood how iron deficiency causes AC, but it is known that it causes a degree of immunocompromise (decreased efficiency of the immune system) which may in turn allow an opportunistic infection of candida. Vitamin B2 deficiency (ariboflavinosis) may also cause AC, and other conditions such as redness of mucous membranes, magenta colored glossitis (pink inflammation of the tongue). Vitamin B5 deficiency may also cause AC, along with glossitis, and skin changes similar to seborrhoeic dermatitis around the eyes, nose and mouth. Vitamin B12 deficiency is sometimes responsible for AC, and commonly occurs together with folate deficiency (a lack of folic acid), which also causes glossitis and megaloblastic anemia. Vitamin B3 deficiency (pellagra) is another possible cause, and in which other association conditions such as dermatitis, diarrhea, dementia and glossitis can occur. Biotin (vitamin B7) deficiency has also been reported to cause AC, along with hair loss (alopecia) and dry eyes. Zinc deficiency is known to cause AC. Other symptoms may include diarrhea, alopecia and dermatitis. Acrodermatitis enteropathica is an autosomal recessive genetic disorder causing impaired absorption of zinc, and is associated with AC.In general, these nutritional disorders may be caused by malnutrition, such as may occur in alcoholism or in poorly considered diets, or by malabsorption secondary to gastrointestinal disorders (e.g. Coeliac disease or chronic pancreatitis) or gastrointestinal surgeries (e.g. pernicious anemia caused by ileal resection in Crohns disease).

Systemic disorders
Some systemic disorders are involved in angular cheilitis by virtue of their association with malabsorption and the creation of nutritional deficiencies described above. Such examples include people with anorexia nervosa.  Other disorders may cause lip enlargement (e.g. orofacial granulomatosis), which alters the local anatomy and extenuates the skin folds at the corners of the mouth. More still may be involved because they affect the immune system, allowing normally harmless organisms like Candida to become pathogenic and cause an infection. Xerostomia (dry mouth) is thought to account for about 5% of cases of AC. Xerostomia itself has many possible causes, but commonly the cause may be side effects of medications, or conditions such as Sjögrens syndrome. Conversely, conditions which cause drooling or sialorrhoea (excessive salivation) can cause angular cheilitis by creating a constant wet environment in the corners of the mouth. About 25% of people with Down syndrome appear to have AC. This is due to relative macroglossia, an apparently large tongue in a small mouth, which may constantly stick out of the mouth causing maceration of the corners of the mouth with saliva. Inflammatory bowel diseases (such as Crohns disease or ulcerative colitis) can be associated with angular cheilitis. In Crohns, it is likely the result of malabsorption and immunosuppressive therapy which gives rise to the sores at the corner of the mouth. Glucagonomas are rare pancreatic endocrine tumors which secrete glucagon, and cause a syndrome of dermatitis, glucose intolerance, weight loss and anemia. AC is a common feature of glucagonoma syndrome. Infrequently, angular cheilitis may be one of the manifestations of chronic mucocutaneous candidiasis, and sometimes cases of oropharyngeal or esophageal candidiasis may accompany angular cheilitis. Angular cheilitis may be present in human immunodeficiency virus infection, neutropenia, or diabetes. Angular cheilitis is more common in people with eczema because their skin is more sensitive to irritants. Other conditions possibly associated include plasma cell gingivitis, Melkersson–Rosenthal syndrome, or sideropenic dysphagia (also called Plummer–Vinson syndrome or Paterson–Brown–Kelly syndrome).

Drugs
Several drugs may cause AC as a side effect, by various mechanisms, such as creating drug-induced xerostomia. Various examples include isotretinoin, indinavir, and sorafenib. Isotretinoin (Accutane), an analog of vitamin A, is a medication which dries the skin. Less commonly, angular cheilitis is associated with primary hypervitaminosis A, which can occur when large amounts of liver (including cod liver oil and other fish oils) are regularly consumed or as a result from an excess intake of vitamin A in the form of vitamin supplements. Recreational drug users may develop AC. Examples include cocaine, methamphetamine, heroin, and hallucinogens.

Allergic contact dermatitis
Allergic reactions may account for about 25–34% of cases of generalized cheilitis (i.e., inflammation not confined to the angles of the mouth). It is unknown how frequently allergic reactions are responsible for cases of angular cheilitis, but any substance capable of causing generalized allergic cheilitis may present involving the corners of the mouth alone.
Examples of potential allergens include substances that may be present in some types of lipstick, toothpaste, acne products, cosmetics, chewing gum, mouthwash, foods, dental appliances, and materials from dentures or mercury containing amalgam fillings. It is usually impossible to tell the difference between irritant contact dermatitis and allergic contact dermatitis without a patch test.

Loss of lower facial height
Severe tooth wear or ill fitting dentures may cause wrinkling at the corners of the lip that creates a favorable environment for the condition. This can be corrected with onlays or crowns on the worn teeth to restore height or new dentures with "taller" teeth. The loss of vertical dimension has been associated with angular cheilitis in older individuals with an increase in facial laxity.

Diagnosis
Angular cheilitis is normally a diagnosis made clinically. If the sore is unilateral, rather than bilateral, this suggests a local factor (e.g., trauma) or a split syphilitic papule. Angular cheilitis caused by mandibular overclosure, drooling, and other irritants is usually bilateral.The lesions are normally swabbed to detect if Candida or pathogenic bacterial species may be present. Persons with angular cheilitis who wear dentures often also will have their denture swabbed in addition. A complete blood count (full blood count) may be indicated, including assessment of the levels of iron, ferritin, vitamin B12 (and possibly other B vitamins), and folate.

Classification
Angular cheilitis could be considered to be a type of cheilitis or stomatitis. Where Candida species are involved, angular cheilitis is classed as a type of oral candidiasis, specifically a primary (group I) Candida-associated lesion. This form angular cheilitis which is caused by Candida is sometimes termed "Candida-associated angular cheilitis", or less commonly, "monilial perlèche". Angular cheilitis can also be classified as acute (sudden, short-lived appearance of the condition) or chronic (lasts a long time or keeps returning), or refractory (the condition persists despite attempts to treat it).

Management
There are four aspects to the treatment of angular cheilitis. Firstly, potential reservoirs of infection inside the mouth are identified and treated. Oral candidiasis, especially denture-related stomatitis is often found to be present where there is angular cheilitis, and if it is not treated, the sores at the corners of the mouth may often recur. This involves having dentures properly fitted and disinfected. Commercial preparations are marketed for this purpose, although dentures may be left in dilute (1:10 concentration) household bleach overnight, but only if they are entirely plastic and do not contain any metal parts, and with rinsing under clean water before use. Improved denture hygiene is often required thereafter, including not wearing the denture during sleep and cleaning it daily. For more information, see Denture-related stomatitis.
Secondly, there may be a need to increase the vertical dimension of the lower face to prevent overclosure of the mouth and formation of deep skin folds. This may require the construction of a new denture with an adjusted bite. Rarely, in cases resistant to normal treatments, surgical procedures such as collagen injections (or other facial fillers such as autologous fat or crosslinked hyaluronic acid) are used in an attempt to restore the normal facial contour. Other measures which seek to reverse the local factors that may be contributing to the condition include improving oral hygiene, stopping smoking or other tobacco habits and use of a barrier cream (e.g. zinc oxide paste) at night.Thirdly, treatment of the infection and inflammation of the lesions themselves is addressed. This is usually with topical antifungal medication, such as clotrimazole, amphotericin B, ketoconazole, or nystatin cream. Some antifungal creams are combined with corticosteroids such as hydrocortisone or triamcinolone to reduce inflammation, and certain antifungals such as miconazole also have some antibacterial action. Diiodohydroxyquinoline is another topical therapy for angular cheilitis </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Retinoblastoma and can you explain it in depth? [/INST] Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children.Though most children survive this cancer, they may lose their vision in the affected eye(s) or need to have the eye removed.Almost half of children with retinoblastoma have a hereditary genetic defect associated with retinoblastoma. In other cases, it is caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein).

Signs and symptoms
Retinoblastoma is universally known as the most intrusive intraocular cancer among children. The chance of survival and preservation of the eye depends fully on the severity. Retinoblastoma is extremely rare as there are only about 200 to 300 cases every year in the United States. Looking at retinoblastoma globally, only 1 in about 15,000 children have this malignancy but these numbers continuously increase.Intraocular malignancies are more curable rather than extraocular malignancies due to early diagnosis and an early treatment prognosis. During infant screenings, if they incorporate an eye screening like they do a hearing screening, it can be detected at an earlier age, therefore, preventing its spread. Leucocoria is the primary indication of retinoblastoma and is when the cancer is still intraocular, meaning inside the eye. When light is reflected by the white tumor, the view of the red retina is blocked. Retinoblastoma can be curable after the initial sign and up to six months, if the tumor is intraocular. If you do not visit an ophthalmologist with signs of leucocoria within a reasonable amount of time, the delay in the diagnosis could lead to a more severe prognosis. Due to a delay in the diagnosis, it could result in proptosis which is then considered extraocular, the most severe.The most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cats eye reflex. Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding.Depending on the position of the tumors, they may be visible during a simple eye exam using an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only with an examination under anesthetic (EUA). A white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats disease.The presence of the photographic fault red eye in only one eye and not in the other may be a sign of retinoblastoma. A clearer sign is "white eye" or "cats eye" (leukocoria).

Cause
Mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body. Alterations in RB1 or MYCN can give rise to retinoblastoma.

RB1
In children with the heritable genetic form of retinoblastoma, a mutation occurs in the RB1 gene on chromosome 13. RB1 was the first tumor suppressor gene cloned. Although RB1 interacts with over 100 cell proteins, its negative regulator effect on the cell cycle principally arises from binding and inactivation of the transcription factor E2F, thus repressing the transcription of genes which are required for the S phase.The defective RB1 gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. The expression of the RB1 allele is autosomal dominant with 90% penetrance.Inherited forms of retinoblastomas are more likely to be bilateral. In addition, inherited uni- or bilateral retinoblastomas may be associated with pineoblastoma and other malignant midline supratentorial primitive neuroectodermal tumors (PNETs) with a dismal outcome; retinoblastoma concurrent with a PNET is known as trilateral retinoblastoma. A 2014 meta-analysis showed that 5-year survival of trilateral retinoblastoma increased from 6% before 1995 to 57% by 2014, attributed to early detection and improved chemotherapy.The development of retinoblastoma can be explained by the two-hit model. According to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors. The first mutational event can be inherited (germline or constitutional), which will then be present in all cells in the body. The second “hit” results in the loss of the remaining normal allele (gene) and occurs within a particular retinal cell. In the sporadic, nonheritable form of retinoblastoma, both mutational events occur within a single retinal cell after fertilization (somatic events); sporadic retinoblastoma tends to be unilateral.
Several methods have been developed to detect the RB1 gene mutations.  Attempts to correlate gene mutations to the stage at presentation have not shown convincing evidence of a correlation.

MYCN
Not all retinoblastoma cases are with RB1 inactivation. There are cases reported with only one RB1 mutation or even two functional RB1 alleles, which indicates other oncogenic lesions of retinoblastoma. Somatic amplification of the MYCN oncogene is responsible for some cases of nonhereditary, early-onset, aggressive, unilateral retinoblastoma. MYCN can act as a transcription factor and promotes proliferation by regulating the expression of cell cycle genes. Although MYCN amplification accounted for only 1.4% of retinoblastoma cases, researchers identified it in 18% of infants diagnosed at less than 6 months of age. Median age at diagnosis for MYCN retinoblastoma was 4.5 months, compared with 24 months for those who had nonfamilial unilateral disease with two RB1 gene mutations.

Diagnosis
Screening for retinoblastoma should be part of a "well baby" screening for newborns during the first 3 months of life, to include:
The red reflex: checking for a normal reddish-orange reflection from the eyes retina with an ophthalmoscope or retinoscope from about 30 cm or 1 foot, usually done in a dimly lit or dark room
The corneal light reflex or Hirschberg test: checking for symmetrical reflection of beam of light in the same spot on each eye when a light is shined into each cornea, to help determine whether the eyes are crossed
Eye examination: checking for any structural abnormalities

Classification
The two forms of the disease are a heritable form and nonheritable form (all cancers are considered genetic in that mutations of the genome are required for their development, but this does not imply that they are heritable, or transmitted to offspring). Around 55% of children with retinoblastoma have the nonheritable form. If no history of the disease exists within the family, the disease is labeled "sporadic", but this does not necessarily indicate that it is the nonheritable form. Bilateral retinoblastomas are commonly heritable, while unilateral retinoblastomas are commonly nonheritable.In about two-thirds of cases, only one eye is affected (unilateral retinoblastoma); in the other third, tumors develop in both eyes (bilateral retinoblastoma). The number and size of tumors on each eye may vary. In certain cases, the pineal gland or the suprasellar or parasellar region (or in very rare cases other midline intracranial locations) is also affected (trilateral retinoblastoma). The position, size, and quantity of tumors are considered when choosing the type of treatment for the disease.

Differential diagnosis
1. Persistent hyperplastic primary vitreous is a congenital developmental anomaly of the eye resulting from failure of the embryological, primary vitreous, and hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and may present with whitening of the pupil.
2. Coats disease is a typically unilateral disease characterised by abnormal development of blood vessels behind the retina, leading to blood vessel abnormalities in the retina and retinal detachment to mimic retinoblastoma.
3. Toxocariasis is a parasitic disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment.
4. Retinopathy of prematurity is associated with low-birth-weight infants who receive supplemental oxygen in the period immediately after birth, and it involves damage to the retinal tissue and may lead to retinal detachment.If the eye examination is abnormal, further testing may include imaging studies, such as computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound. CT and MRI can help define the structure abnormalities and reveal any calcium depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain.

Morphology
Gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes, Homer Wright rosettes,  and fleurettes from photoreceptor differentiation.

Genetic testing
Identifying the RB1 gene mutation that led to a childs retinoblastoma can be important in the clinical care of  the affected individual and in the care of (future) siblings and offspring. It may run in the family.

Bilaterally affected individuals  and 13-15% of unilaterally affected individuals, are expected to show an RB1 mutation in blood.  By identifying the RB1 mutation in the affected individual, (future) siblings, children, and other relatives can be tested for the mutation; if they do not carry the mutation, child relatives are not at risk of retinoblastoma, so need not undergo the trauma and expense of examinations under anaesthetic.  For the 85% of unilaterally affected  patients found not to carry either of their eye tumor RB1 mutations  in blood, neither molecular  testing nor clinical surveillance of siblings is required.
If  the  RB1 mutation of an affected individual is identified, amniotic cells in an at-risk pregnancy can be tested for the family  mutation;  any fetus that carries the mutation can be delivered early, allowing early treatment of any eye tumors, leading to better visual outcomes.
For cases of unilateral retinoblastoma where no eye tumor  is available for testing, if no RB1 mutation is detected in blood after high-sensitivity molecular testing (i.e. >93% RB1 mutation detection sensitivity),  the risk of a germline RB1 mutation is reduced to less than 1%, a level at which only clinic examination (and not examinations under anaesthetic) is recommended for the affected individual and their future offspring (National Retinoblastoma Strategy, Canadian Guidelines for Care).

Imaging
Traditional ultrasound B scan can detect calcifications in the tumour while high-frequency ultrasound B scan is able to provide higher resolution than the traditional ultrasound and determine the proximity of the tumour with front portion of the eye. MRI scan can detect high-risk features such as optic nerve invasion; choroidal invasion, scleral invasion, and intracranial invasion. CT scan is generally avoided because radiation can stimulate the formation of more eye tumours in those with RB1 genetic mutation.

Staging
In order to properly diagnose retinoblastoma, there must be guidelines to follow to properly classify the risk of the tumor. The Reese Ellsworth Classification System, by Dr. Algernon Reese and Dr. Robert Ellsworth, is universally used to determine the size, location, and multi-focality of the tumor. The system was originally used to decide the best treatment result by using external beam radiotherapy, as well as, the likeliness of salvaging the globe of the eye. Due to chemotherapy not being part of the Reese Ellsworth Classification System, there needed to be an updated classification system to foresee the treatment outcomes of chemotherapy. The International Classification for Intraocular Retinoblastoma is now the current system being used, and it was created by Murphree and associates. According to Reese and Ellsworth, there were different groups that had various features in order to classify the globe salvage as very favorable to the category of very unfavorable. In order to salvage the affected eye, the disc diameter had to be around 4DD and behind the equator to have higher favorability. If the tumor was around ten in disc diameter and involved roughly 50% of the retina, it was considered unfavorable to salvage the globe which could result in enucleation. According to Murphree, the different groups were classified from very low risk to very high risk which was determined by features of the given tumor. Very low risk means that the tumor has to be less than 3mm and there must be no seeding of the vitreous or sub-retinal area. When a patient is very high risk, the tumor presents itself with multiple features and is going to have to be treated with conservative treatment modalities or enucleation.
International Classification for Intraocular Retinoblastoma

Treatment
The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist. Correct treatment also depends on the mutation type, whether it is a germline RB1 mutation, a sporadic RB1 mutation or MYCN amplification with functional RB1. Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies).
The various treatment modalities for retinoblastoma includes:
Enucleation of the eye – Most patients with unilateral disease present with advanced intraocular disease, so usually undergo enucleation, which results in a cure rate of 95%. In bilateral Rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision.
External beam radiotherapy (EBR) – The most common indication for EBR is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pityriasis rosea and can you explain it in depth? [/INST] Pityriasis rosea is a type of skin rash. Classically, it begins with a single red and slightly scaly area known as a "herald patch". This is then followed, days to weeks later, by an eruption of many smaller scaly spots; pinkish with a red edge in people with light skin and greyish in darker skin. About 20% of cases show atypical deviations from this pattern. It usually lasts less than three months and goes away without treatment. Sometimes malaise or a fever may occur before the start of the rash or itchiness, but often there are few other symptoms.While the cause is not entirely clear, it is believed to be related to human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7). It does not appear to be contagious. Certain medications may result in a similar rash. Diagnosis is based on the symptoms.Evidence for specific treatment is limited. About 1.3% of people are affected at some point in time. It most often occurs in those between the ages of 10 and 35. The condition was described at least as early as 1798.

Signs and symptoms
The symptoms of this condition include:

Recent upper respiratory tract infections in 8–69% of patients have been reported by some studies.
Occasionally, prodromal flu-like symptoms, including headache, joint pain, mild fever, and fatigue, as well as gastrointestinal symptoms such as nausea, diarrhea, or vomiting, and feeling generally unwell, precede other symptoms.
In most cases, a single, 2 to 10 cm (1" to 4") oval red "herald" patch appears, classically on the trunk or neck, having an appearance similar to ringworm. Occasionally, the herald patch may occur in a hidden position (in the armpit, for example) and not be noticed immediately. The herald patch may also appear as a cluster of smaller oval spots, and be mistaken for acne. Rarely, it does not become present at all.
After the herald patch appears, usually some days or weeks later, a rash of many small (5–10 mm; 1⁄4" to 1⁄2") pink or red, flaky, oval or round spots appear. They are mostly situated on the trunk and upper limbs. They follow the skins cleavage lines, which on the upper chest and back produce a characteristic "christmas-tree" distribution.
In 6% of cases an "inverse" distribution may occur, with rash mostly on the extremities. In children, presentation can be atypical or inverse, and the course is typically milder.
About one in four people with PR have mild to severe symptomatic itching. (Moderate itching due to skin over-dryness is much more common, especially if soap is used to cleanse the affected areas.) The itching is often non-specific, and worsens if scratched. This tends to fade as the rash develops and does not usually last through the entire course of the disease.About a fifth of cases have an atypical form, with significant variations in symptoms including the size, distribution, morphology, and evolution of the lesions. In addition to typical papules and scales, forms appearing as very large plaques (pityriasis rosea gigantea), urticaria, large blisters, patches resembling erythema multiforme, oral lesions, and various other appearances have been noted. A vesicular form can mimic chicken pox. Variations in distribution include inverted forms, with rashes on the face or extremities without appearing on the trunk, as well as more uncommon versions localized to the armpits, groin, or extremities (pityriasis rosea circinata et marginata of Vidal) or unilateral spread.

Causes
The cause of pityriasis rosea is not certain, but its clinical presentation and immunologic reactions suggest a viral infection as a cause. Some believe it to be a  reactivation of herpes viruses 6 and 7, which cause roseola in infants, though some investigations have found no evidence of this.

Diagnosis
Experienced practitioners may make the diagnosis clinically. Classical symptoms are usually straightforward to recognize, but the wide range of atypical forms may cause difficulty for the clinician in diagnosing some cases. Misdiagnosis by nondermatologists is not uncommon. If the diagnosis is in doubt, tests may be performed to rule out similar conditions such as Lyme disease, ringworm, guttate psoriasis, nummular or discoid eczema, drug eruptions, other viral exanthems. The clinical appearance of pityriasis rosea in some cases is similar to that of secondary syphilis, and rapid plasma reagin testing should be performed if there is any clinical concern for syphilis. A biopsy of the lesions will show extravasated erythrocytes within dermal papillae and dyskeratotic cells within the dermis.A set of validated diagnostic criteria for pityriasis rosea is as follows:
A patient is diagnosed as having pityriasis rosea if:

On at least one occasion or clinical encounter, the patient has all the essential clinical features and at least one of the optional clinical features, and
On all occasions or clinical encounters related to the rash, the patient does not have any of the exclusional clinical features.The essential clinical features are the following:
Discrete circular or oval lesions,
Scaling on most lesions, and
Peripheral collarette scaling with central clearance on at least two lesions.The optional clinical features are the following:
Truncal and proximal limb distribution, with less than 10% of lesions distal to mid-upper-arm and mid-thigh,
Orientation of most lesions along skin cleavage lines, and
A herald patch (not necessarily the largest) appearing at least two days before eruption of other lesions, from history of the patient or from clinical observation.The exclusional clinical features are the following:
Multiple small vesicles at the centre of two or more lesions,
Two or more lesions on palmar or plantar skin surfaces, and
Clinical or serological evidence of secondary syphilis.

Treatment
The condition usually resolves on its own, and treatment is not required. Oral antihistamines or topical steroids may be used to decrease itching. Steroids do provide relief from itching, and improve the appearance of the rash, but they also cause the new skin that forms (after the rash subsides) to take longer to match the surrounding skin color. While no scarring has been found to be associated with the rash, scratching should be avoided </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Bowel obstruction and can you explain it in depth? [/INST] Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs and symptoms include abdominal pain, vomiting, bloating and not passing gas. Mechanical obstruction is the cause of about 5 to 15% of cases of severe abdominal pain of sudden onset requiring admission to hospital.Causes of bowel obstruction include adhesions, hernias, volvulus, endometriosis, inflammatory bowel disease, appendicitis, tumors, diverticulitis, ischemic bowel, tuberculosis and intussusception. Small bowel obstructions are most often due to adhesions and hernias while large bowel obstructions are most often due to tumors and volvulus. The diagnosis may be made on plain X-rays; however, CT scan is more accurate. Ultrasound or MRI may help in the diagnosis of children or pregnant women.The condition may be treated conservatively or with surgery. Typically intravenous fluids are given, a tube is placed through the nose into the stomach to decompress the intestines, and pain medications are given. Antibiotics are often given. In small bowel obstruction about 25% require surgery. Complications may include sepsis, bowel ischemia and bowel perforation.About 3.2 million cases of bowel obstruction occurred in 2015 which resulted in 264,000 deaths. Both sexes are equally affected and the condition can occur at any age. Bowel obstruction has been documented throughout history, with cases detailed in the Ebers Papyrus of 1550 BC and by Hippocrates.

Signs and symptoms
Depending on the level of obstruction, bowel obstruction can present with abdominal pain, swollen abdomen, abdominal distension, and constipation. Bowel obstruction may be complicated by dehydration and electrolyte abnormalities due to vomiting; respiratory compromise from pressure on the diaphragm by a distended abdomen, or aspiration of vomitus; bowel ischemia or perforation from prolonged distension or pressure from a foreign body.In small bowel obstruction, the pain tends to be colicky (cramping and intermittent) in nature, with spasms lasting a few minutes. The pain tends to be central and mid-abdominal. Vomiting may occur before constipation.In large bowel obstruction, the pain is felt lower in the abdomen and the spasms last longer. Constipation occurs earlier and vomiting may be less prominent. Proximal obstruction of the large bowel may present as small bowel obstruction.

Causes
Small bowel obstruction
Causes of small bowel obstruction include:
Adhesions from previous abdominal surgery (most common cause)
Barbed sutures
Pseudoobstruction
Hernias containing bowel
Crohns disease causing adhesions or inflammatory strictures
Neoplasms, benign or malignant
Intussusception
Volvulus
Superior mesenteric artery syndrome, a compression of the duodenum by the superior mesenteric artery and the abdominal aorta
Ischemic strictures
Foreign bodies (e.g. gallstones in gallstone ileus, swallowed objects such as expandable water toys)
Intestinal atresiaAfter abdominal surgery, the incidence of small bowel obstruction from any cause is 9%. In those where the cause of the obstruction was clear, adhesions are the single most common cause (more than half).

Large bowel obstruction
Causes of large bowel obstruction include:
Neoplasms / cancer
Diverticulitis / Diverticulosis
Hernias
Inflammatory bowel disease
Colonic volvulus (sigmoid, caecal, transverse colon)
Adhesions
Constipation
Fecal impaction
Fecaloma
Colon atresia
Intestinal pseudoobstruction
Endometriosis
Narcotic induced (especially with the large doses given to cancer or palliative care patients)

Outlet obstruction
Outlet obstruction is a sub-type of large bowel obstruction and refers to conditions affecting the anorectal region that obstruct defecation, specifically conditions of the pelvic floor and anal sphincters. Outlet obstruction can be classified into four groups.
Functional outlet obstruction
Inefficient inhibition of the internal anal sphincter
Short-segment Hirschsprungs disease
Chagas disease
Hereditary internal sphincter myopathy
Inefficient relaxation of the striated pelvic floor muscles
Anismus (pelvic floor dyssynergia)
Multiple sclerosis
Spinal cord lesions
Mechanical outlet obstruction
Internal intussusception
Enterocele
Dissipation of force vector
rectocele
Descending perineum
Rectal prolapse
Impaired rectal sensitivity
Megarectum
Rectal hyposensitivity

Diagnosis
The main diagnostic tools are blood tests, X-rays of the abdomen, CT scanning, and ultrasound. If a mass is identified, biopsy may determine the nature of the mass.Radiological signs of bowel obstruction include bowel distension and the presence of multiple (more than six) gas-fluid levels on supine and erect abdominal radiographs. Ultrasounds may be as useful as CT scanning to make the diagnosis.Contrast enema or small bowel series or CT scan can be used to define the level of obstruction, whether the obstruction is partial or complete, and to help define the cause of the obstruction. The appearance of water-soluble contrast in the cecum on an abdominal radiograph within 24 hours of it being given by mouth predicts resolution of an adhesive small bowel obstruction with sensitivity of 97% and specificity of 96%.Colonoscopy, small bowel investigation with ingested camera or push endoscopy, and laparoscopy are other diagnostic options.

Differential diagnosis
Differential diagnoses of bowel obstruction include:

Ileus
Pseudo-obstruction or Ogilvies syndrome
Intra-abdominal sepsis
Pneumonia or other systemic illness

Treatment
Some causes of bowel obstruction may resolve spontaneously; many require operative treatment. In adults, frequently the surgical intervention and the treatment of the causative lesion are required. In malignant large bowel obstruction, endoscopically placed self-expanding metal stents may be used to temporarily relieve the obstruction as a bridge to surgery, or as palliation. Diagnosis of the type of bowel obstruction is normally conducted through initial plain radiograph of the abdomen, luminal contrast studies, computed tomography scan, or ultrasonography prior to determining the best type of treatment.Further research is needed to find out if parenteral nutrition is of benefit to people with an inoperable blockage of the bowel caused by advanced cancer.

Small bowel obstruction
In the management of small bowel obstructions, a commonly quoted surgical aphorism is: "never let the sun rise or set on small-bowel obstruction" because about 5.5% of small bowel obstructions are ultimately fatal if treatment is delayed. Improvements in radiological imaging of small bowel obstructions allow for confident distinction between simple obstructions, that can be treated conservatively, and obstructions that are surgical emergencies (volvulus, closed-loop obstructions, ischemic bowel, incarcerated hernias, etc.).A small flexible tube (nasogastric tube) may be inserted through the nose into the stomach to help decompress the dilated bowel. This tube is uncomfortable but relieves the abdominal cramps, distention, and vomiting. Intravenous therapy is utilized and the urine output is monitored with a catheter in the bladder.Most people with SBO are initially managed conservatively because in many cases, the bowel will open up. Some adhesions loosen up and the obstruction resolves. The patient is examined several times a day, and X-ray images are made to ensure he or she is not getting clinically worse.Conservative treatment involves insertion of a nasogastric tube, correction of dehydration and electrolyte abnormalities </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Uterine prolapse and can you explain it in depth? [/INST] Uterine prolapse is when the uterus descends towards or through the opening of the vagina. Symptoms may include vaginal fullness, pain with sex, trouble urinating, urinary incontinence, and constipation. Often it gets worse over time. Low back pain and vaginal bleeding may also occur.Risk factors include pregnancy, childbirth, obesity, constipation, and chronic coughing. Diagnosis is based on examination. It is a form of pelvic organ prolapse, together with bladder prolapse, large bowel prolapse, and small bowel prolapse.Preventive efforts include managing chronic breathing problems, not smoking, and maintaining a healthy weight. Mild cases may be treated with a pessary together with hormone replacement therapy. More severe cases may require surgery such as a vaginal hysterectomy. About 14% of women are affected. It occurs most commonly after menopause.

Causes
The most common cause of uterine prolapse is trauma during childbirth, in particular multiple or difficult births. About 50% of women who have had children develop some form of pelvic organ prolapse in their lifetime. It is more common as women get older, particularly in those who have gone through menopause. This condition is surgically correctable.

Pathophysiology
The uterus (womb) is normally held in place by a hammock of muscles and ligaments </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Occupational asthma and can you explain it in depth? [/INST] Occupational asthma is new onset asthma or the recurrence of previously quiescent asthma directly caused by exposure to an agent at workplace. It is an occupational lung disease and a type of work-related asthma. Agents that can induce occupational asthma can be grouped into sensitizers and irritants.Sensitizer-induced occupational asthma is an immunologic form of asthma which occurs due to inhalation of specific substances (i.e., high-molecular-weight proteins from plants and animal origins, or low-molecular-weight agents that include chemicals, metals and wood dusts) and occurs after a latency period of several weeks to years.Irritant-induced (occupational) asthma is a non-immunologic form of asthma that results from a single or multiple high dose exposure to irritant products. It is usually develops early after exposure; however can also develop insidiously over a few months after a massive exposure to a complex mixture of alkaline dust and combustion products, as shown in the World Trade Center disaster. Unlike those with sensitizer-induced occupational asthma, subjects with irritant-induced occupational asthma do not develop work-related asthma symptoms after re-exposure to low concentrations of the irritant that initiated the symptoms. Reactive airways dysfunction syndrome (RADS) is a severe form of irritant induced asthma where respiratory symptoms usually develop in the minutes or hours after a single accidental inhalation of a high concentration of irritant gas, aerosol, vapor, or smoke.Another type of work-related asthma is work-exacerbated asthma (WEA) which is asthma worsened by workplace conditions but not caused by it. WEA is present in about a fifth of patients with asthma and a wide variety of conditions at work, including irritant chemicals, dusts, second-hand smoke, common allergens that may be present at work, as well as other "exposures" such as emotional stress, worksite temperature, and physical exertion can exacerbate asthma symptoms in these patients. Both occupational asthma and work-exacerbated asthma can be present in an individual.
A number of diseases have symptoms that mimic occupational asthma, such as asthma due to nonoccupational causes, chronic obstructive pulmonary disease (COPD), irritable larynx syndrome, hyperventilation syndrome, hypersensitivity pneumonitis, and bronchiolitis obliterans.

Signs and symptoms
Like other types of asthma, it is characterized by airway inflammation, reversible airways obstruction, and bronchospasm, but it is caused by something in the workplace environment. Symptoms include shortness of breath, tightness of the chest, coughing, sputum production and wheezing. Some patients may also develop upper airway symptoms such as itchy eyes, tearing, sneezing, nasal congestion and rhinorrhea.Symptoms may develop over many years as in sensitizer induced asthma or may occur after a single exposure to a high-concentration agent as in case of RADS.

Risk factors
At present, over 400 workplace substances have been identified as having asthmagenic or allergenic properties. Agents such as flour, diisocyanates, latex, persulfate salts, aldehydes, animals, wood dusts, metals, enzymes usually account for the majority cases, however, the distribution of causal agents may vary widely across geographic areas, depending on the pattern of industrial activities. For example, in France the industries most affected are bakeries and cake-shops, automobile industry and hairdressers, whereas in Canada the principal cause is wood dust, followed by isocyanates. Furthermore, the most common cause of occupational asthma in the workplace are isocyanates. Isocyanates are used in the production of motor vehicles and in the application of orthopaedic polyurethane and fibreglass casts.The occupations most at risk are: adhesive handlers (e.g. acrylate), animal handlers and veterinarians (animal proteins), bakers and millers (cereal grains), carpet makers (gums), electronics workers (soldering resin), forest workers, carpenters and cabinetmakers (wood dust), hairdressers (e.g. persulfate), health care workers (latex and chemicals such as glutaraldehyde), janitors and cleaning staff (e.g. chloramine-T), pharmaceutical workers (drugs, enzymes), seafood processors, shellac handlers (e.g. amines), solderers and refiners (metals), spray painters, insulation installers, plastics and foam industry workers (e.g. diisocyanates), textile workers (dyes) and users of plastics and epoxy resins (e.g. anhydrides)The following tables show occupations that are known to be at risk for occupational asthma, the main reference for these is the Canadian Centre for Occupational Health and Safety.

Diagnosis
To diagnose occupational asthma it is necessary to confirm the symptoms of asthma and establish the causal connection with the work environment.  Various diagnostic tests can be used to aid in diagnoses of work related asthma.A spirometer is a device used to measure timed expired and inspired volumes, and can be used to help diagnose asthma.
Peak expiratory flow rate (PEFR) is a hand held device which measures  how fast a person can exhale and is a reliable test for occupational asthma. Serial PEFR can be measured to see if there is a difference in ability to exhale at work compared to that in a controlled environment.
A non-specific bronchial hyperreactivity test can be used to support the diagnose occupational asthma. It involves measuring the forced expiratory volume in 1 second (FEV-1) of the patient before and after exposure to methacholine or mannitol. Presence of airway responsiveness i.e. significant drop in FEV-1 can be seen in patients with occupational asthma.Specific inhalation challenges test consist of exposing the subjects to the suspected occupational agent in the laboratory and/or at the workplace and assess for asthma symptoms as well as a reduction in FEV1.Other tests such as skin prick test, serum immunologic testing and measurement of sputum eosinophils can also be useful in establishing the diagnosis of occupational asthma.

Prevention
Several forms of preventive measures have been suggested to prevent development of occupational asthma and also detect risk or disease early to allow intervention and improve outcomes. These include: comprehensive programs, education and training, medical examinations, use of medications, reduction of exposures and elimination of exposures.

Asthma symptoms and airway hyperresponsiveness can persist for several years after removal from the offending environment </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Asbestosis and can you explain it in depth? [/INST] Asbestosis is long-term inflammation and scarring of the lungs due to asbestos fibers. Symptoms may include shortness of breath, cough, wheezing, and chest tightness. Complications may include lung cancer, mesothelioma, and pulmonary heart disease.Asbestosis is caused by breathing in asbestos fibers. It requires a relatively large exposure over a long period of time, which typically only occur in those who directly work with asbestos. All types of asbestos fibers are associated with an increased risk. It is generally recommended that currently existing and undamaged asbestos be left undisturbed. Diagnosis is based upon a history of exposure together with medical imaging. Asbestosis is a type of interstitial pulmonary fibrosis.There is no specific treatment. Recommendations may include influenza vaccination, pneumococcal vaccination, oxygen therapy, and stopping smoking. Asbestosis affected about 157,000 people and resulted in 3,600 deaths in 2015. Asbestos use has been banned in a number of countries in an effort to prevent disease.Statistics from the Health and Safety Executive showed that in 2019, there were 490 asbestosis deaths.

Signs and symptoms
The signs and symptoms of asbestosis typically manifest after a significant amount of time has passed following asbestos exposure, often several decades under current conditions in the US. The primary symptom of asbestosis is generally the slow onset of shortness of breath, especially with physical activity. Clinically advanced cases of asbestosis may lead to respiratory failure. When a stethoscope is used to listen to the lungs of a person with asbestosis, they may hear inspiratory "crackles".
The characteristic pulmonary function finding in asbestosis is a restrictive ventilatory defect. This manifests as a reduction in lung volumes, particularly the vital capacity (VC) and total lung capacity (TLC). The TLC may be reduced through alveolar wall thickening; however, this is not always the case. Large airway function, as reflected by FEV1/FVC, is generally well preserved. In severe cases, the drastic reduction in lung function due to the stiffening of the lungs and reduced TLC may induce right-sided heart failure (cor pulmonale). In addition to a restrictive defect, asbestosis may produce reduction in diffusion capacity and a low amount of oxygen in the blood of the arteries.

Cause
The cause of asbestosis is the inhalation of microscopic asbestos mineral fibers suspended in the air. In the 1930s, E. R. A. Merewether found that greater exposure resulted in greater risk.

Pathogenesis
Asbestosis is the scarring of lung tissue (beginning around terminal bronchioles and alveolar ducts and extending into the alveolar walls) resulting from the inhalation of asbestos fibers. There are two types of fibers: amphibole (thin and straight) and serpentine (curly). All forms of asbestos fibers are responsible for human disease as they are able to penetrate deeply into the lungs.  When such fibers reach the alveoli (air sacs) in the lung, where oxygen is transferred into the blood, the foreign bodies (asbestos fibers) cause the activation of the lungs local immune system and provoke an inflammatory reaction dominated by lung macrophages that respond to chemotactic factors activated by the fibers. This inflammatory reaction can be described as chronic rather than acute, with a slow ongoing progression of the immune system attempting to eliminate the foreign fibers. Macrophages phagocytose (ingest) the fibers and stimulate fibroblasts to deposit connective tissue.
Due to the asbestos fibers natural resistance to digestion, some macrophages are killed and others release inflammatory chemical signals, attracting further lung macrophages and fibrolastic cells that synthesize fibrous scar tissue, which eventually becomes diffuse and can progress in heavily exposed individuals. This tissue can be seen microscopically soon after exposure in animal models.   Some asbestos fibers become layered by an iron-containing proteinaceous material (ferruginous body) in cases of heavy exposure where about 10% of the fibers become coated.  Most inhaled asbestos fibers remain uncoated.  About 20% of the inhaled fibers are transported by cytoskeletal components of the alveolar epithelium to the interstitial compartment of the lung where they interact with macrophages and mesenchymal cells. The cytokines, transforming growth factor beta and tumor necrosis factor alpha, appear to play major roles in the development of  scarring inasmuch as the process can be blocked in animal models by preventing the expression of the growth factors. The result is fibrosis in the interstitial space, thus asbestosis.
This fibrotic scarring causes alveolar walls to thicken, which reduces elasticity and gas diffusion, reducing oxygen transfer to the blood as well as the removal of carbon dioxide.  This can result in shortness of breath, a common symptom exhibited by individuals with asbestosis. Those with asbestosis may be more vulnerable to tumor growth (mesothelioma) because asbestos decreases the cytotoxicity of natural killer cells and impairs the functioning of T helper cells, which detect abnormal cell growth.

Diagnosis
According to the American Thoracic Society (ATS), the general diagnostic criteria for asbestosis are:
Evidence of structural pathology consistent with asbestosis, as documented by imaging or histology
Evidence of causation by asbestos as documented by the occupational and environmental history, markers of exposure (usually pleural plaques), recovery of asbestos bodies, or other means
Exclusion of alternative plausible causes for the findingsThe abnormal chest x-ray and its interpretation remain the most important factors in establishing the presence of pulmonary fibrosis. The findings usually appear as small, irregular parenchymal opacities, primarily in the lung bases. Using the ILO Classification system, "s", "t", and/or "u" opacities predominate. CT or high-resolution CT (HRCT) are more sensitive than plain radiography at detecting pulmonary fibrosis (as well as any underlying pleural changes). More than 50% of people affected with asbestosis develop plaques in the parietal pleura, the space between the chest wall and lungs. Once apparent, the radiographic findings in asbestosis may slowly progress or remain static, even in the absence of further asbestos exposure. Rapid progression suggests an alternative diagnosis.
Asbestosis resembles many other diffuse interstitial lung diseases, including other pneumoconiosis. The differential diagnosis includes idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, sarcoidosis, and others. The presence of pleural plaques may provide supportive evidence of causation by asbestos. Although lung biopsy is usually not necessary, the presence of asbestos bodies in association with pulmonary fibrosis establishes the diagnosis. Conversely, interstitial pulmonary fibrosis in the absence of asbestos bodies is most likely not asbestosis. Asbestos bodies in the absence of fibrosis indicate exposure, not disease.

Treatment
There is no cure available for asbestosis. Oxygen therapy at home is often necessary to relieve the shortness of breath and correct underlying low blood oxygen levels. Supportive treatment of symptoms includes respiratory physiotherapy to remove secretions from the lungs by postural drainage, chest percussion, and vibration. Nebulized medications may be prescribed in order to loosen secretions or treat underlying chronic obstructive pulmonary disease. Immunization against pneumococcal pneumonia and annual influenza vaccination is administered due to increased sensitivity to the diseases. Those with asbestosis are at increased risk for certain cancers. If the person smokes, quitting the habit reduces further damage. Periodic pulmonary function tests, chest x-rays, and clinical evaluations, including cancer screening/evaluations, are given to detect additional hazards.

Society and culture
Legal issues
The death of English textile worker Nellie Kershaw in 1924 from pulmonary asbestosis was the first case to be described in medical literature, and the first published account of disease attributed to occupational asbestos exposure. However, her former employers (Turner Brothers Asbestos) denied that asbestosis even existed because the medical condition was not officially recognised at the time. As a result, they accepted no liability for her injuries and paid no compensation, either to Kershaw during her final illness or to her family after her death. Even so, the findings of the inquest into her death were highly influential insofar as they led to a parliamentary enquiry by the British Parliament. The enquiry formally acknowledged the existence of asbestosis, recognised that it was hazardous to health and concluded that it was irrefutably linked to the prolonged inhalation of asbestos dust. Having established the existence of asbestosis on a medical and judicial basis, the report resulted in the first Asbestos Industry Regulations being published in 1931, which came into effect on 1 March 1932.The first lawsuits against asbestos manufacturers occurred in 1929.  Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the link between asbestos, asbestosis and mesothelioma became known (some reports seem to place this as early as 1898 in modern times).  The liability resulting from the sheer number of lawsuits and people affected has reached billions of U.S. dollars.  The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.
To date, about 100 companies have declared bankruptcy at least partially due to asbestos-related liability. In accordance with Chapter 11 and § 524(g) of the U.S. federal bankruptcy code, a company may transfer its liabilities and certain assets to an asbestos personal injury trust, which is then responsible for compensating present and future claimants. Since 1988, 60 trusts have been established to pay claims with about $37 billion in total assets. From 1988 through 2010, analysis from the United States Government Accountability Office indicates that trusts have paid about 3.3 million claims valued at about $17.5 billion.

Notable people
This is a partial list of notable people who have died from lung fibrosis associated with asbestos:

Bernie Banton, social justice advocate
Paul Gleason, Breakfast Club actor
Stephen Jay Gould, Harvard University professor, paleontologist, evolutionary biologist, and historian
Nellie Kershaw, first person diagnosed with asbestos-related disease, 1924
John MacDougall, politician
Steve McQueen, actor
Theodore Sturgeon, writer

References
External links

"Asbestos Toxicity". ATSDR Case Studies in Environmental Medicine. U.S. Department of Health and Human Services.
"Asbestos health and safety". British Government Health and Safety Executive.
"Asbestos Exposure" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Toxic multinodular goitre and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Anorectal abscess and can you explain it in depth? [/INST] Anorectal abscess (also known as an anal/rectal abscess, or perianal/perirectal abscess) is an abscess adjacent to the anus.  Most cases of perianal abscesses are sporadic, though there are certain situations which elevate the risk for developing the disease, such as diabetes mellitus, Crohns disease, chronic corticosteroid treatment and others. It arises as a complication of paraproctitis. Ischiorectal, inter- and intrasphincteric abscesses have been described.

Signs and symptoms
Pain in the perianal area is the most common symptom of an anorectal abscess. The pain may be dull, aching, or throbbing. It is worst when the person sits down and right before a bowel movement. After the individual has a bowel movement, the pain usually lessens. Other signs and symptoms of anorectal abscess include constipation, drainage from the rectum, fever and chills, or a palpable mass near the anus.

The condition can become extremely painful, and usually worsens over the course of just a few days. The pain may be limited and sporadic at first, but may worsen to a constant pain which can become very severe when body position is changed (e.g., when standing up, rolling over, and so forth). Depending upon the exact location of the abscess, there can also be excruciating pain during bowel movements, though this is not always the case. This condition may occur in isolation, but is frequently indicative of another underlying disorder, such as Crohns disease.

Complications
If left untreated, an anal fistula will almost certainly form, connecting the rectum to the skin. This requires more intensive surgery. Furthermore, any untreated abscess may (and most likely will) continue to expand, eventually becoming a serious systemic infection.

Cause
Abscesses are caused by a high-density infection of (usually) common bacteria which collect in one place or another for any variety of reasons.  Anal abscesses, without treatment, are likely to spread and affect other parts of the body, particularly the groin and rectal lumen.  All abscesses can progress to serious generalized infections requiring lengthy hospitalizations if not treated.
Historically, many rectal abscesses are caused by bacteria common in the digestive system, such as E. coli. While this still continues often to be the case, there has recently been an increase in the causative organism being staphylococcus, as well as the difficult to treat community-acquired methicillin-resistant S. aureus. Because of the increasing appearance of more exotic bacteria in anal abscesses, microbiological examination will always be performed on the surgical exudate to determine the proper course of any antibiotic treatment.

Diagnosis
Diagnosis of anorectal abscess begins with a medical history and physical exam. Imaging studies which can help determine the diagnosis in cases of a deep non-palpable perirectal abscess include pelvic CT scan, MRI or trans-rectal ultrasound. These studies are not necessary, though, in cases which the diagnosis can be made upon physical exam.

Classification
Anorectal abscesses are classified according to their anatomic location and the following are the most common types: perianal abscess, ischiorectal abscess, intersphincteric abscess and supralevator abscess.
Perianal abscess, which represents the most common type of anorectal abscesses accounting for about 60% of reported cases, are superficial collections of purulent material just beneath the skin of the anal canal.Ischiorectal abscess is formed when suppuration transverses the external anal sphincter into the ischiorectal space.Intersphincteric abscess results from suppuration contained between the internal and external anal sphincters.Supralevator abscess forms from cephalad extension of the intersphincteric abscess above the levator ani or from caudal extension of a suppurative abdominal process like appendicitis, diverticular or gynaecologic sepsis.

Differential diagnosis
This condition is often initially misdiagnosed as hemorrhoids, since this is almost always the cause of any sudden anal discomfort. The presence of the abscess, however, is suspected when the pain quickly worsens over one or two days and usual hemorrhoid treatments are ineffective in bringing relief.  Furthermore, any serious abscess will eventually begin to cause signs and symptoms of general infection, including fever and nighttime chills.
A physician can rule out a hemorrhoid with a simple visual inspection, and usually appreciate an abscess by touch.

Treatment
Anal abscesses are rarely treated with a simple course of antibiotics </s>