<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Necrophilia and explain in detail? [/INST] Necrophilia, also known as necrophilism, necrolagnia, necrocoitus, necrochlesis, and thanatophilia, is sexual attraction towards or a sexual act involving corpses. It is classified as a paraphilia by the World Health Organization (WHO) in its International Classification of Diseases (ICD) diagnostic manual, as well as by the American Psychiatric Association in its Diagnostic and Statistical Manual (DSM).

Origins of term
Various terms for the crime of corpse-violation animate sixteenth- through nineteenth-century works on law and legal medicine. The plural term "nécrophiles" was coined by Belgian physician Joseph Guislain in his lecture series, Leçons Orales Sur Les Phrénopathies, given around 1850, about the contemporary necrophiliac François Bertrand:
It is within the category of the destructive madmen [aliénés destructeurs] that one needs to situate certain patients to whom I would like to give the name of necrophiliacs [nécrophiles]. The alienists have adopted, as a new form, the case of Sergeant Bertrand, the disinterrer of cadavers on whom all the newspapers have recently reported. However, dont think that we are dealing here with a form of phrenopathy which appears for the first time. The ancients, in speaking about lycanthropy, have cited examples to which one can more or less relate the case which has just now attracted the public attention so strongly.
Psychiatrist Bénédict Morel popularised the term about a decade later when discussing Bertrand.

History
In the ancient world, sailors returning corpses to their home country were often accused of necrophilia. Singular accounts of necrophilia in history are sporadic, though written records suggest the practice was present within Ancient Egypt. Herodotus writes in The Histories that, to discourage intercourse with a corpse, ancient Egyptians left deceased beautiful women to decay for "three or four days" before giving them to the embalmers. Herodotus also alluded to suggestions that the Greek tyrant Periander had defiled the corpse of his wife, employing a metaphor: "Periander baked his bread in a cold oven." Acts of necrophilia are depicted on ceramics from the Moche culture, which reigned in northern Peru from the first to eighth century CE. A common theme in these artifacts is the masturbation of a male skeleton by a living woman. Hittite law from the 16th century BC through to the 13th century BC explicitly permitted sex with the dead. In what is now Northeast China, the ethnic Xianbei emperor Murong Xi (385–407) of the Later Yan state had intercourse with the corpse of his beloved empress Fu Xunying, after the latter was already cold and put into the coffin.In Renaissance Italy, following the reputed moral collapse brought about by the Black Death and before the Roman Inquisition of the Counter-Reformation, literature was replete with sexual references; these include necrophilia, as in the epic poem Orlando Innamorato by Matteo Maria Boiardo, first published in 1483. In a notorious modern example, American serial killer Jeffrey Dahmer was a necrophiliac. Dahmer wanted to create a sex slave who would mindlessly consent to whatever he wanted. When his attempts failed, and his male victim died, he would keep the corpse until it decomposed beyond recognition,  masturbating and performing sexual intercourse on the body. He would perform sexual activities before and after murdering his victims. Dahmer explained that he only killed his victims because he did not want them to leave.
More modern necrophiliacs include Scottish serial killer Dennis Nilsen, and English David Fuller, who is considered the worst offender of this kind in English legal history.Havelock Ellis, in his 1903 volume of Studies of the Psychology of Sex, believed that necrophilia was related to algolagnia, in that both involve the transformation of a supposed negative emotion, such as anger, fear, disgust, or grief, into sexual desire.

Classification
In the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), recurrent, intense sexual interest in corpses can be diagnosed under Other Specified Paraphilic Disorder (necrophilia) when it causes marked distress or impairment in important areas of functioning.Forensic Psychologist Anil Aggrawal introduced a ten tier classification of necrophiliacs based on increasing severity of disorder.
Additionally, criminologist Lee Mellors typology of homicidal necrophiliacs consists of eight categories (A–H) and is based on the combination of two behavioural axes: destructive (offender mutilates the corpse for sexual reasons) – preservative (offender does not), and cold (offender used the corpse sexually two hours or more after death) – warm (offender used the corpse sexually less than two hours after death). This renders four categories (A-D) to which Mellor adds an additional four (E-H):

Category A (cold/destructive), e.g. Ted Bundy, Jeffrey Dahmer
Category B (cold/preservative), e.g. Gary Ridgway, Dennis Nilsen, Carl Tanzler
Category C (warm/destructive) e.g. Andrei Chikatilo, Joseph Vacher
Category D (warm/preservative) e.g. Robert Yates, Earle Nelson
Category E (dabblers) e.g. Richard Ramirez, Mark Dixie
Category F (catathymic — impulsively and explosively lashing out)
Category G (exclusive necromutilophiles) e.g. Robert Napper, Peter Sutcliffe
Category H (sexual cannibals & vampires) e.g. Albert Fish, Peter KürtenDabblers have transitory opportunistic sexual relations with corpses, but do not prefer them. Catathymic necrophiliacs commit postmortem sex acts only while in a sudden impulsive state. Exclusive necromutilophiles derive pleasure purely from mutilating the corpse, while sexual cannibals and vampires are sexually aroused by eating human body parts. Category A, C, and F offenders may also cannibalise or drink the blood of their victims.

Research
Humans
Necrophilia is often assumed to be rare, but no data for its prevalence in the general population exists. Some necrophiliacs only fantasise about the act, without carrying it out.  In 1958, Klaf and Brown commented that, although rarely described, necrophiliac fantasies may occur more often than is generally supposed.Rosman and Resnick (1989) reviewed 123 cases of necrophilia. The sample was divided into genuine necrophiliacs, who had a persistent attraction to corpses, and pseudo-necrophiliacs, who acted out of opportunity, sadism, or transient interest.  Of the total, 92% were male and 8% were female. 57% of the genuine necrophiliacs had occupational access to corpses, with morgue attendants, hospital orderly, and cemetery employees being the most common jobs. The researchers theorised that either of the following situations could be antecedents to necrophilia:
The necrophiliac develops poor self-esteem, perhaps due in part to a significant loss;
(a) They are very fearful of rejection by others and they desire a sexual partner who is incapable of rejecting them; and/or
(b) They are fearful of the dead, and transform their fear—by means of reaction formation—into a desire.
They develop an exciting fantasy of sex with a corpse, sometimes after exposure to a corpse.

Motives
The most common motive for necrophiliacs is the possession of a partner who is unable to resist or reject them. However, in the past, necrophiliacs have expressed having more than one motive.The authors reported that of their sample of 34 genuine necrophiliacs:
68% were motivated by a desire for a non-resisting and non-rejecting partner
21% were motivated by a want for a reunion with a lost partner
15% were motivated by sexual attraction to dead people
15% were motivated by a desire for comfort or to overcome feelings of isolation
12% were motivated by a desire to remedy low self-esteem by expressing power over a corpseLesser common motives include:

Unavailability of a living partner
Compensation for a fear of women
Belief that sex with a living woman is a mortal sin
Need to achieve a feeling of total control over a sexual partner
Compliance with a command hallucination
Performance of a series of destructive acts
Expression of polymorphous perverse sexual desires
Need to perform limitless sexual activityIQ data was limited, but not abnormally low. About half of the sample had a personality disorder, and 11% of true necrophiliacs were psychotic. Rosman and Resnick concluded that their data challenged the conventional view of necrophiliacs as generally psychotic, mentally deficient, or unable to obtain a consenting partner.

Other animals
Necrophilia has been observed in mammals, birds, reptiles and frogs. In 1960, Robert Dickerman described necrophilia in ground squirrels, which he termed "Davian behaviour" in reference to a limerick about a necrophiliac miner named Dave. The label is still used for necrophilia in animals. Certain species of arachnids and insects practice sexual cannibalism, where the female cannibalises her male mate before, during, or after copulation.
Kees Moeliker made an observation while he was sitting in his office at the Natural History Museum Rotterdam, when he heard the distinctive thud of a bird hitting the glass facade of the building. Upon inspection, he discovered a drake (male) mallard lying dead outside the building. Next to the downed bird, a second drake mallard was standing close by. As Moeliker observed the couple, the living drake pecked at the corpse of the dead one for a few minutes then mounted the corpse and began copulating with it. The act of necrophilia lasted for about 75 minutes, in which time, according to Moeliker, the living drake took two short breaks before resuming with copulating behaviour. Moeliker surmised that at the time of the collision with the window the two mallards were engaged in a common pattern in duck behaviour called "attempted rape flight". "When one died the other one just went for it and didnt get any negative feedback – well, didnt get any feedback," according to Moeliker. Necrophilia had previously only been reported in heterosexual mallard pairs.In a short paper known as "Sexual Habits of the Adélie Penguin", deemed too shocking for contemporary publication, George Murray Levick described "little hooligan bands" of penguins mating with dead females in the Cape Adare rookery, the largest group of Adélie penguins, in 1911 and 1912. This is nowadays ascribed to lack of experience of young penguins; a dead female, with eyes half-closed, closely resembles a compliant female. A gentoo penguin was observed attempting to have intercourse with a dead penguin in 1921.A male New Zealand sea lion was once observed attempting to copulate with a dead female New Zealand fur seal in the wild. The sea lion nudged the seal repeatedly, then mounted her and made several pelvic thrusts. Approximately ten minutes later, the sea lion became disturbed by the researchers presence, dragged the corpse of the seal into the water, and swam away while holding it. A male sea otter was observed holding a female sea otter underwater until she drowned before repeatedly copulating with her carcass. Several months later, the same sea otter was again observed copulating with the carcass of a different female. Copulation with a dead female pilot whale by a captive male pilot whale has been observed, and possible sexual behaviour between two male humpback whales, one dead, has also been reported.In 1983, a male rock dove was observed to be copulating with the corpse of a dove that shortly before had its head crushed by a car. In 2001, a researcher laid out sand martin corpses to attract flocks of other sand martins. In each of six trials, 1–5 individuals from flocks of 50–500 were observed attempting to copulate with the dead sand martins. This occurred one to two months after the breeding season; since copulation outside the breeding season is uncommon among birds, the researcher speculated that the lack of resistance by the corpses stimulated the behaviour. Charles Brown observed at least ten cliff swallows attempt to copulate with a road-killed cliff swallow in the space of 15 minutes. He commented, "This isnt the first time Ive seen cliff swallows do this; the bright orange rump sticking up seems to be all the stimulus these birds need." Necrophilia has also been reported in the European swallow, grey-backed sparrow-lark, Starks lark, and the snow goose. A Norwegian television report showed a male hybrid between a black grouse and western capercaillie kill a male black grouse before attempting to copulate with it. In 2015, due to work done by the University of Washington, it was found that crows would commit necrophilia on dead crow corpses in about 4% of encounters with corpses.

Necrophilia has been documented in various lizard species, including  Ameiva ameiva, the leopard lizard, and Holbrookia maculata. There are two reports of necrophilic behaviour in the sleepy lizard (Tiliqua rugosa). In one, the partner of a male lizard got caught in fencing wire and died. The male continued to display courtship behaviour towards his partner two days after her death. This lizards necrophilia was believed to stem from its strong monogamous bond. In one study of black and white tegu lizards, two different males were observed attempting to court and copulate with a single female corpse on two consecutive days. On the first day, the corpse was freshly dead, but by the second day it was bloating and emitting a strong putrid odor. The researcher attributed the behaviour to sex pheromones still acting on the carcass.Male garter snakes often copulate with dead females. One case has been reported in the Bothrops jararaca snake with a dead South American rattlesnake. The prairie rattlesnake (Crotalus viridis) and Helicops carinicauda snake have both been seen attempting to mate with decapitated females, presumably attracted by still-active sex pheromones. Male crayfish sometimes copulate with dead crayfish of either sex, and in one observation with a dead crayfish of a different species.In anurans, it has been observed in the foothill yellow-legged frog, the yellow fire-bellied toad, the common frog, the Oregon spotted frog, the common Asian Toad, Dendropsophus columbianus, and Rhinella jimi. The film Cane Toads: An Unnatural History shows a male toad copulating with a female toad that had been run over by a car for eight hours. Necrophilic amplexus in frogs may occur because males will mount any pliable object the size of an adult female. If the mounted object is a live frog not appropriate for mating, it will vibrate its body or vocalise a call to be released. Dead frogs cannot do this, so they may be held for hours. The Amazonian frog Rhinella proboscidea sometimes practices what has been termed "functional necrophilia": a male grasps the corpse of a dead female and squeezes it until its oocytes are ejected before fertilising them.

Treatment
Treatment for necrophilia is similar to that prescribed for most paraphilias. Besides advocating treatment of the associated psychopathology, there is little known on the treatment of necrophilia. There has not been a sufficient number of necrophiliacs to establish any effective treatments. However, based on the available data, clinicians are suggested to:

Determine whether or not a patient has necrophilia
Treat any psychopathology that is associated with necrophilia
Establish psycho-therapeutic rapport
Provide male patients with heightened sex drives with anti-androgens
Help patients find a normal sexual relationship
Help divert the necrophilic fantasies to a living object via desensitization

Case studies
Jeffrey Dahmer
Serial killer Jeffrey Dahmer (1960–1994) was known to perform oral sex or masturbate, or both, upon the corpses of his victims before dismembering them. In unguarded, taped interviews with his defense attorney, Wendy Patrickus, Jeffrey Dahmer explicitly stated that he had sex with his victims before and after their deaths. He explained that he wanted to remain with the person as long as possible, preserving some of his victims selected organs, skeletal tissue and bones.

Ted Bundy
Ted Bundy (1946–1989) was an American serial killer who raped and murdered at least 30 young women during the 1970s. He also confessed to participating in necrophilic acts, claiming to have chosen secluded disposal sites for his victims bodies specifically for post-mortem sexual intercourse.

Karen Greenlee
In 1987, Karen Greenlee gave a detailed interview called “The Unrepentant Necrophile” for Jim Mortons (edited by Adam Parafrey) book Apocalypse Culture. In this interview, she stated that she had a preference for younger men and was attracted to the smell of blood and death. She considered necrophilia an addiction. The interview was held in her apartment, which was apparently a small studio filled with books, necrophilic drawings, and satanic adornments. She also had written a confession letter in which she claimed to have abused 20–40 male corpses.

Dennis Nilsen
Dennis Nilsen (1945–2018) was a Scottish serial killer who had developed an association between death and intimacy, later finding posing as a corpse a source of sexual arousal. In 1978, Nilsen committed his first murder and had intercourse with the victims corpse, keeping the body for months before disposal. Nilsen was reported to have sexually abused the corpses of various victims until his arrest.

Legality
Australia
Necrophilia is not explicitly mentioned in Australian law; however, under the Crimes Act 1900 – Sect 81C, penalised for misconduct with regard to corpses is any person who:(a) indecently interferes with any dead human body, or
(b) improperly interferes with, or offers any indignity to, any dead human body or human remains (whether buried or not), and

shall be liable to imprisonment for two years.

Brazil
Article 212 of the Brazilian Penal Code (federal Decree-Law No 2.848) states as follows:
Art. 212 – To abuse a cadaver or its ashes:Penalty: detention, from 1 to 3 years, plus fine.
Although sex with a corpse is not explicitly mentioned, a person who has sex with a corpse may be convicted of a crime under the above Article. The legal asset protected by such Article is not the corpses objective honour, but the feeling of good memories, respect, and veneration that living people keep about the deceased person: these persons are considered passive subjects of the corpses violation.

India
Section 297 of the Indian Penal Code entitled "Trespassing on burial places, etc.", states as follows:
Whoever, with the intention of wounding the feelings of any person, or of insulting the religion of any person, or with the knowledge that the feelings of any person are likely to be wounded, or that the religion of any person is likely to be insulted thereby,
commits any trespass in any place of worship or on any place of sculpture, or any place set apart from the performance of funeral rites or as a depository for the remains of the dead, or offers any indignity to any human corpse, or causes disturbance to any persons assembled for the performance of funeral ceremonies, shall be punished with imprisonment of either description for a term which may extend to one year, or with fine, or with both.
Although sex with a corpse is not explicitly mentioned, a person who has sex with a corpse may be convicted under the above section. Section 377 of the Indian Penal Code can also be invoked.

Philippines
There are no laws which explicitly prohibit sexual acts on corpses. The closest applicable law is the provision in the Revised Penal Code which only criminalizes "defamation to blacken the memory of one who is dead". There were at least efforts to introduce bills criminalizing sexual acts on corpses during the 15th Congress; one by which penalizes sexual acts of males of corpses of women, and another which covers sexual intercourse, anal sex, and oral sex done on corpses. Both proposals penalizes the act with fine and imprisonment.

New Zealand
Under Section 150 of the New Zealand Crimes Act 1961, it is an offence for there to be "misconduct in respect to human remains". Subsection (b) elaborates that this applies if someone "improperly or indecently interferes with or offers indignity to any dead human body or human remains, whether buried or not". This statute is therefore applicable to sex with corpses and carries a potential two-year prison sentence, although there is no relevant case law.

South Africa
Section 14 of the Criminal Law (Sexual Offences and Related Matters) Amendment Act, 2007 prohibits the commission of a sexual act with a corpse. Until codified by the act it was a common law offence.

Sweden
Section 16, § 10 of the Swedish Penal Code criminalises necrophilia, but it is not explicitly mentioned. Necrophilia falls under the regulations against abusing a corpse or grave (Brott mot griftefrid), which carries a maximum sentence of two years in prison. One person has been convicted of necrophilia. He was sentenced to psychiatric care for that and other crimes, including arson.

United Kingdom
Sexual penetration of a corpse was made illegal under the Sexual Offences Act 2003, carrying a maximum sentence of two years imprisonment. Prior to 2003, necrophilia was not illegal; however, exposing a naked corpse in public was classed as a public nuisance (R v. Clark [1883] 15 Cox 171).

United States
There is no federal legislation specifically barring sex with a corpse. Multiple states have their own laws:

See also
Incidents of necrophilia
Necrophilia in popular culture
Vulnerability and care theory of love
Death during consensual sex
Somnophilia
Paraphilias

Footnotes
Sources
Aggrawal, Anil (2010). Necrophilia: Forensic and Medico-legal Aspects. Boca Raton, Florida: CRC Press. ISBN 978-1420089127.
Aggrawal, Anil (19 April 2016). Necrophilia: Forensic and Medico-legal Aspects. CRC Press. ISBN 978-1-4200-8913-4.
Finbow, Steve (2014). Grave Desire: A Cultural History of Necrophilia. Winchester, UK: Zero Books. ISBN 978-1-7827-9342-7.
Lee Mellor (2016) Homicide: A Forensic Psychology Casebook. CRC Press. ISBN 9781498731522.
Purcell, Catherine; Arrigo, Bruce A. (7 June 2006). The Psychology of Lust Murder: Paraphilia, Sexual Killing, and Serial Homicide </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Eccrine nevus and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Patellar tendinitis and explain in detail? [/INST] Patellar tendinitis, also known as jumpers knee, is an overuse injury of the tendon that straightens the knee. Symptoms include pain in the front of the knee. Typically the pain and tenderness is at the lower part of the kneecap, though the upper part may also be affected. Generally there is no pain when the person is at rest. Complications may include patellar tendon rupture.Risk factors include being involved in athletics and being overweight. It is particularly common in athletes who are involved in jumping sports such as basketball and volleyball. The underlying mechanism involves small tears in the tendon connecting the kneecap with the shinbone. Diagnosis is generally based on symptoms and examination. Other conditions that can appear similar include infrapatellar bursitis, chondromalacia patella and patellofemoral syndrome.Treatment often involves resting the knee and physical therapy. Evidence for treatments, including rest, however is poor. Recovery can take between months and persist over years. It is relatively common with about 14% of athletes currently affected; however research reflects that more than half of athletes with this injury end their careers as a result. Males are more commonly affected than females. The term "jumpers knee" was coined in 1973.

Signs and symptoms
People report anterior knee pain, often with an aching quality. The symptom onset is insidious. Rarely is a discrete injury described. Usually, the problem is below the kneecap but it may also be above. Jumpers knee can be classified into 1 of 4 stages, as follows:Stage 1 – Pain only after activity, without functional impairment
Stage 2 – Pain during and after activity, although the person is still able to perform satisfactorily in his or her sport
Stage 3 – Prolonged pain during and after activity, with increasing difficulty in performing at a satisfactory level
Stage 4 – Complete tendon tear requiring surgical repair
It begins as inflammation in the patellar tendon where it attaches to the patella and may progress by tearing or degenerating the tendon. People present with an ache over the patella tendon. Most people are between 10 and 16 years old.  Magnetic resonance imaging can reveal edema (increased T2 signal intensity) in the proximal aspect of the patellar tendon.

Causes
It is an overuse injury from repetitive overloading of the extensor mechanism of the knee. The microtears exceed the bodys healing mechanism unless the activity is stopped.Among the risk factors for patellar tendonitis are low ankle dorsiflexion, weak gluteal muscles, and muscle tightness, particularly in the calves, quadriceps muscle, and hamstrings.It may be associated with stiff ankle movement and ankle sprains.

Diagnosis
Diagnosis is generally based on symptoms and a physical examination. Ultrasound or magnetic resonance imaging may help clarify how severe the problem is.

Treatment
Evidence for treatment is poor.  In the early stages rest, ice, compression, and elevation may be tried </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Primary cutaneous immunocytoma and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Orbital lymphoma and explain in detail? [/INST] Orbital lymphoma is a common type of non-Hodgkin lymphoma that occurs near or on the eye. Common symptoms include decreased vision and uveitis. Orbital lymphoma can be diagnosed via a biopsy of the eye and is usually treated with radiotherapy or in combination with chemotherapy.

Types
There are two main types of intraocular lymphomas: primary central nervous system involvement (PCNSL) and primary central nervous system with ocular involvement (PCNSLO). The difference between PCNSL and PCNSLO is that PNSCL involves the central nervous system, while PCNSLO does not. 56-86% of orbital lymphomas are classified PCNSL and 15-25% are classified PCNSLO.PCNSLO is common in people who are severely immunosuppressed.
Symptoms of this form of ocular lymphoma include painless decreased vision, sensitivity to light, a red eye, and floaters </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Subacute sclerosing panencephalitis and explain in detail? [/INST] Subacute sclerosing panencephalitis (SSPE)—also known as Dawson disease—is a rare form of chronic, progressive brain inflammation caused by slow infection with certain defective strains of hypermutated measles virus. The condition primarily affects children, teens, and young adults. It has been estimated that about 2 in 10,000 people who get measles will eventually develop SSPE. However, a 2016 study estimated that the rate for unvaccinated infants under 15 months was as high as 1 in 609. No cure for SSPE exists, and the condition is almost always fatal. SSPE should not be confused with acute disseminated encephalomyelitis, which can also be caused by the measles virus, but has a very different timing and course.SSPE is caused by the wild-type virus, not by vaccine strains.

Signs and symptoms
SSPE is characterized by a history of primary measles infection, followed by an asymptomatic period that lasts 7 years on average but can range from 1 month to 27 years. After the asymptomatic period, progressive neurological deterioration occurs, characterized by behavior change, intellectual problems, myoclonic seizures, blindness, ataxia, and eventually death.

Progression
Symptoms progress through the following 4 stages:
Stage 1: There may be personality changes, mood swings, or depression. Fever, headache, and memory loss may also be present. This stage may last up to 6 months.
Stage 2: This stage may involve jerking, muscle spasms, seizures, loss of vision, and dementia.
Stage 3: Jerking movements are replaced by writhing (twisting) movements and rigidity. At this stage, complications may result in blindness or death.
Stage 4: Progressive loss of consciousness into a persistent vegetative state, which may be preceded by or concomitant with paralysis, occurs in the final stage, during which breathing, heart rate, and blood pressure are affected. Death usually occurs as a result of fever, heart failure, or the brain’s inability to control the autonomic nervous system.

Pathogenesis
A large number of nucleocapsids are produced in the neurons and the glial cells. In these cells the viral genes that encode envelope proteins have restricted expression. As a result, infectious particles like the M protein are not produced, and the virus is able to survive persistently without evoking an immune response. Eventually the infection will lead to SSPE.

Diagnosis
According to the Merck Manual: "SSPE is suspected in young patients with dementia and neuromuscular irritability. EEG, CT or MRI, CSF examination, and measles serologic testing are done. EEG shows periodic complexes with high-voltage diphasic waves occurring synchronously throughout the recording. CT or MRI may show cortical atrophy or white matter lesions. CSF examination usually reveals normal pressure, cell count, and total protein content; however, CSF globulin is almost always elevated, constituting up to 20 to 60% of CSF protein. Serum and CSF contain elevated levels of measles virus antibodies. Anti-measles IgG appears to increase as the disease progresses.
If test results are inconclusive, brain biopsy may be needed."

Treatment
If the diagnosis is made during stage 1 it may be possible to treat the disease with oral isoprinosine (Inosiplex) and intraventricular interferon alfa, but the response to these drugs varies from patient to patient, and the only accepted treatments are supportive measures such as anticonvulsants. Following onset of stage 2, the disease is invariably fatal.

Prognosis
In the classic presentation of the disease death occurs in 1 to 3 years, but faster and slower progressions can occur </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Speech disorder and explain in detail? [/INST] Speech disorders or speech impairments are a type of communication disorder in which normal speech is disrupted. This can mean stuttering, lisps, etc. Someone who is unable to speak due to a speech disorder is considered mute. Speech is a complex process that requires precise timing, nerve and muscle control, and as a result is susceptible to impairments. Speech disorders affect roughly 11.5% of the US population, and may be caused by a stroke, an accident or birth defect.

Classification
Classifying speech into normal and disordered is more problematic than it first seems. By strict classification, only 5% to 10% of the population has a completely normal manner of speaking (with respect to all parameters) and healthy voice; all others have one disorder or another.
There are three different levels of classification when determining the magnitude and type of a speech disorder and the proper treatment or therapy:
Sounds the patient can produce
Phonemic – can be produced easily; used meaningfully and constructively
Phonetic – produced only upon request; not used consistently, meaningfully, or constructively; not used in connected speech
Stimulate sounds
Easily stimulated
Stimulate after demonstration and probing (i.e. with a tongue depressor)
Cannot produce the sound
Cannot be produced voluntarily
No production ever observed

Types of disorder
Apraxia of speech may result from stroke or progressive illness, and involves inconsistent production of speech sounds and rearranging of sounds in a word ("potato" may become "topato" and next "totapo"). Production of words becomes more difficult with effort, but common phrases may sometimes be spoken spontaneously without effort.
Cluttering, a speech and fluency disorder characterized primarily by a rapid rate of speech, which makes speech difficult to understand.
Developmental verbal dyspraxia also known as childhood apraxia of speech.
Dysarthria is a weakness or paralysis of speech muscles caused by damage to the nerves or brain. Dysarthria is often caused by strokes, Parkinsons disease, ALS, head or neck injuries, surgical accident, or cerebral palsy.
Aphasia
Dysprosody is an extremely rare neurological speech disorder. It is characterized by alterations in intensity, in the timing of utterance segments, and in rhythm, cadence, and intonation of words. The changes to the duration, the fundamental frequency, and the intensity of tonic and atonic syllables of the sentences spoken, deprive an individuals particular speech of its characteristics. The cause of dysprosody is usually associated with neurological pathologies such as brain vascular accidents, cranioencephalic traumatisms, and brain tumors.
Muteness is the complete inability to speak.
Speech sound disorders involve difficulty in producing specific speech sounds (most often certain consonants, such as /s/ or /r/), and are subdivided into articulation disorders (also called phonetic disorders) and phonemic disorders. Articulation disorders are characterized by difficulty learning to produce sounds physically. Phonemic disorders are characterized by difficulty in learning the sound distinctions of a language, so that one sound may be used in place of many </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pulmonary-renal syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Subacute bacterial endocarditis and explain in detail? [/INST] Subacute bacterial endocarditis, abbreviated SBE, is a type of endocarditis (more specifically, infective endocarditis). Subacute bacterial endocarditis can be considered a form of type III hypersensitivity.

Signs and symptoms
Among the signs of subacute bacterial endocarditis are:
Malaise
Weakness
Excessive sweat
Fever

Causes
It is usually caused by a form of Viridans group streptococcus bacteria that normally live in the mouth (Streptococcus mutans, mitis, sanguis or milleri).Other strains of streptococci can cause subacute endocarditis as well. These include streptococcus intermedius, which can cause
acute or subacute infection (about 15% of cases pertaining to infective endocarditis).Enterococci from urinary tract infections and coagulase negative staphylococci can also be causative agents.

Mechanism
The mechanism of subacute bacterial endocarditis could be due to malformed stenotic valves which in the company of bacteremia, become infected, via adhesion and subsequent colonization of the surface area. This causes an inflammatory response, with recruitment of matrix metalloproteinases, and destruction of collagen.Underlying structural valve disease is usually present in patients before developing subacute endocarditis, and is less likely to lead to septic emboli than is acute endocarditis, but subacute endocarditis has a relatively slow process of infection and, if left untreated, can worsen for up to one year before it is fatal. In cases of subacute bacterial endocarditis, the causative organism (streptococcus viridans) needs a previous heart valve disease to colonize. On the other hand, in cases of acute bacterial endocarditis, the organism can colonize on the healthy heart valve, causing the disease.

Diagnosis
Diagnosis of subacute bacterial endocarditis can be done by collecting three blood culture specimens over a 24-hour period for analysis, also it can usually be indicated by the existence of:

Oslers nodes
Roths spots
Nail clubbing

Treatment
The standard treatment is with a minimum of four weeks of high-dose intravenous penicillin with an aminoglycoside such as gentamicin.
The use of high-dose antibiotics is largely based upon animal models.Leo Loewe of Brooklyn Jewish Hospital was the first to successfully treat subacute bacterial endocarditis with penicillin. Loewe reported at the time seven cases of subacute bacterial endocarditis in 1944.

See also
Endocarditis

References
Further references
Goolsby, Mary Jo; Grubbs, Laurie (2011-04-28). Advanced Assessment: Interpreting Findings and Formulating Differential Diagnoses. F.A </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Peripheral ossifying fibroma and explain in detail? [/INST] A peripheral ossifying fibroma, also known as ossifying fibrous epulis, is “a gingival nodule which is composed of a cellular fibroblastic connective tissue stroma which is associated with the formation of randomly dispersed foci of mineralised products, which consists of bone, cementum-like tissue, or a dystrophic calcification. The lesion is considered part of an ossifying fibroma, but that is usually considered to be a jaw tumor.  Because of its overwhelming incidence on the gingiva, the condition is associated with two other diseases, though not because they occur together.  Instead, the three are associated with each other because they appear frequently on gingiva: pyogenic granuloma and peripheral giant cell granuloma.  Some researchers believe peripheral ossifying fibromas to be related to pyogenic fibromas and, in some instances, are the result of a pyogenic granuloma which has undergone fibrosis and calcification.
The term peripheral ossifying fibroma has been criticized as this lesion is not related to the ossifying fibroma of bone and is not a fibroma. This term is used in America, however in Britain, this lesion would be termed a fibrous epulis containing bone.

Signs and symptoms
The color of peripheral ossifying fibromas ranges from red to pink, and is frequently ulcerated.  It can be sessile or pedunculated with the size usually being less than 2 cm </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Oculomotor apraxia and explain in detail? [/INST] Oculomotor apraxia (OMA) is the absence or defect of controlled, voluntary, and purposeful eye movement. It was first described in 1952 by the American ophthalmologist David Glendenning Cogan. People with this condition have difficulty moving their eyes horizontally and moving them quickly. The main difficulty is in saccade initiation, but there is also impaired cancellation of the vestibulo-ocular reflex. Patients have to turn their head in order to compensate for the lack of eye movement initiation in order to follow an object or see objects in their peripheral vision, but they often exceed their target. There is controversy regarding whether OMA should be considered an apraxia, since apraxia is the inability to perform a learned or skilled motor action to command, and saccade initiation is neither a learned nor a skilled action.

Symptoms
Absence of fast phase nystagmus on horizontal optokinetic testing
Problems in nerve function involved in eye movement control, called neuropathy
Inability to visually follow objects
Head thrusts to compensate for the inability to accomplish voluntary horizontal gaze.

Related developmental problems
Even though OMA is not always associated with developmental issues, children with this condition often have hypotonia, decreased muscle tone, and show developmental delays. Some common delays are seen in speech, reading and motor development

Causes
OMA is a neurological condition. Although some brain imaging studies of people with OMA reveal a normal brain, some MRI studies have revealed unusual appearance of some brain areas, in particular the corpus callosum, cerebellum, and/or fourth ventricle. Oculomotor apraxia can be acquired or congenital. Sometimes no cause is found, in which case it is described as idiopathicA person may be born with the parts of the brain for eye movement control not working, or may manifest poor eye movement control in childhood. If any part of the brain that controls eye movement becomes damaged, then OMA may develop.  One of the potential causes is bifrontal hemorrhages. In this case, OMA is associated with bilateral lesions of the frontal eye fields (FEF), located in the caudal middle frontal gyrus. The FEF control voluntary eye movements, including saccades, smooth pursuit and vergence. OMA can also be associated with bilateral hemorrhages in the parietal eye fields (PEF). The PEF surround the posterior, medial segment of the intraparietal sulcus. They have a role in reflexive saccades, and send information to the FEF. Since the FEF and PEF have complementary roles in voluntary and reflexive production of saccades, respectively, and they get inputs from different areas of the brain, only bilateral lesions to both the FEF and PEF will cause persistent OMA.  Patients with either bilateral FEF or bilateral PEF damage (but not both FEF and PEF) have been shown to regain at least some voluntary saccadic initiation some time after their hemorrhages. Other causes of OMA include brain tumors and cardiovascular problems,.

Ataxia with oculomotor apraxia
A subgroup of genetically recessive ataxias associated with OMA has been identified, with an onset during childhood. These are ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia 2 (AOA2), and ataxia telangiectasia. These are autosomal recessive disorders and the associated gene products are involved in DNA repair. Both horizontal and vertical eye movements are affected in these disorders. Although people with either type may have some mild cognitive problems, such as difficulty with concentration or performing multi-step activities, intellectual function is usually not affected.

Type 1
Ataxia-oculomotor apraxia type 1 (AOA1) usually has an onset of symptoms during childhood. It is an autosomal recessive cerebellar ataxia (ARCA) associated with hypoalbuminemia and hypercholesterolemia. Mutations in the gene APTX, which encodes for aprataxin, have been identified to be responsible for AOA1. Elevated creatine kinase is occasionally present, in addition to a sensorimotor axonal neuropathy, as shown by nerve conduction velocity studies. In addition, MRI studies have shown cerebellar atrophy, mild brainstem atrophy, and, in advanced cases, cortical atrophyThe aprataxin protein APTX can remove obstructive termini from DNA strand breaks that interfere with DNA repair. APTX is recruited to DNA single-strand breaks by XRCC1 protein, where it functions as a nick sensor to scan the single-strand breaks for 5’-AMP obstructive termini that are intermediates in failed DNA ligase reactions.  The removal of these obstructions allows DNA repair of the break to be completed.  It is not yet clear which specific single-strand breaks are the neurodegenerative agents in AOA1 patients that lack functional aprataxin protein.  However single-strand breaks with 5’-AMP termini appear to be the most likely candidate lesion.

Type 2
Ataxia-oculomotor apraxia type 2 (AOA2), also known as spinocerebellar ataxia with axonal neuropathy type 2, has its onset during adolescence </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Haemophilia and explain in detail? [/INST] Haemophilia, or hemophilia (from Ancient Greek  αἷμα (haîma) blood, and  φιλία (philía) love of), is a mostly inherited genetic disorder that impairs the bodys ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain. Those with a mild case of the disease may have symptoms only after an accident or during surgery. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a decreased level of consciousness.There are two main types of haemophilia: haemophilia A, which occurs due to low amounts of clotting factor VIII, and haemophilia B, which occurs due to low levels of clotting factor IX. They are typically inherited from ones parents through an X chromosome carrying a nonfunctional gene. Rarely a new mutation may occur during early development or haemophilia may develop later in life due to antibodies forming against a clotting factor. Other types include haemophilia C, which occurs due to low levels of factor XI, Von Willebrand disease, which occur due to low level of a substance called von Willebrand factor in their blood, and parahaemophilia, which occurs due to low levels of factor V. Acquired haemophilia is associated with cancers, autoimmune disorders, and pregnancy. Diagnosis is by testing the blood for its ability to clot and its levels of clotting factors.Prevention may occur by removing an egg, fertilizing it, and testing the embryo before transferring it to the uterus. Human embryos in research can be regarded as the technical object/process. Missing blood clotting factors are replaced to treat haemophilia. This may be done on a regular basis or during bleeding episodes. Replacement may take place at home or in hospital. The clotting factors are made either from human blood or by recombinant methods. Up to 20% of people develop antibodies to the clotting factors which makes treatment more difficult. The medication desmopressin may be used in those with mild haemophilia A. Studies of gene therapy are in early human trials.Haemophilia A affects about 1 in 5,000–10,000, while haemophilia B affects about 1 in 40,000, males at birth. As haemophilia A and B are both X-linked recessive disorders, females are rarely severely affected. Some females with a nonfunctional gene on one of the X chromosomes may be mildly symptomatic. Haemophilia C occurs equally in both sexes and is mostly found in Ashkenazi Jews. In the 1800s haemophilia B was common within the royal families of Europe. The difference between haemophilia A and B was determined in 1952.

Signs and symptoms
Characteristic symptoms vary with severity. In general symptoms are internal or external bleeding episodes, which are called "bleeds". People with more severe haemophilia experience more severe and more frequent bleeds, while people with mild haemophilia usually experience more minor symptoms except after surgery or serious trauma. In cases of moderate haemophilia symptoms are variable which manifest along a spectrum between severe and mild forms.In both haemophilia A and B, there is spontaneous bleeding but a normal bleeding time, normal prothrombin time, normal thrombin time, but prolonged partial thromboplastin time. Internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces. This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement. Bleeding into soft tissues such as muscles and subcutaneous tissues is less severe but can lead to damage and requires treatment.Children with mild to moderate haemophilia may not have any signs or symptoms at birth, especially if they do not undergo circumcision. Their first symptoms are often frequent and large bruises and haematomas from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints, soft tissue, and muscles may also occur. Children with mild haemophilia may not have noticeable symptoms for many years. Often, the first sign in very mild haemophiliacs is heavy bleeding from a dental procedure, an accident, or surgery. Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs.

Complications
Severe complications are much more common in cases of severe and moderate haemophilia. Complications may arise from the disease itself or from its treatment:
Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb.
Joint damage from haemarthrosis (haemophilic arthropathy), potentially with severe pain, disfigurement, and even destruction of the joint and development of debilitating arthritis.
Transfusion transmitted infection from blood transfusions that are given as treatment.
Adverse reactions to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective.
Intracranial haemorrhage is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation, nausea, loss of consciousness, brain damage, and death.Haemophilic arthropathy is characterized by chronic proliferative synovitis and cartilage destruction. If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans. The hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more likely to easily rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis.  In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in  cartilage and bone destruction.

Genetics
Typically, females possess two X-chromosomes, and males have one X and one Y-chromosome. Since the mutations causing the disease are X-linked recessive, a female carrying the defect on one of her X-chromosomes may not be affected by it, as the equivalent dominant allele on her other chromosome should express itself to produce the necessary clotting factors, due to X inactivation. Therefore, heterozygous females are just carriers of this genetic disposition. However, the Y-chromosome in the male has no gene for factors VIII or IX. If the genes responsible for production of factor VIII or factor IX present on a males X-chromosome are deficient there is no equivalent on the Y-chromosome to cancel it out, so the deficient gene is not masked and the disorder will develop.Since a male receives his single X-chromosome from his mother, the son of a healthy female silently carrying the deficient gene will have a 50% chance of inheriting that gene from her and with it the disease; and if his mother is affected with haemophilia, he will have a 100% chance of being a haemophiliac. In contrast, for a female to inherit the disease, she must receive two deficient X-chromosomes, one from her mother and the other from her father (who must therefore be a haemophiliac himself). Hence, haemophilia is expressed far more commonly among males than females, while females, who must have two deficient X-chromosomes in order to have haemophilia, are far more likely to be silent carriers, survive childhood and to submit each of her genetic children to an at least 50% risk of receiving the deficient gene. However, it is possible for female carriers to become mild haemophiliacs due to lyonisation (inactivation) of the X-chromosomes. Haemophiliac daughters are more common than they once were, as improved treatments for the disease have allowed more haemophiliac males to survive to adulthood and become parents. Adult females may experience menorrhagia (heavy periods) due to the bleeding tendency. The pattern of inheritance is criss-cross type. This type of pattern is also seen in colour blindness.A mother who is a carrier has a 50% chance of passing the faulty X-chromosome to her daughter, while an affected father will always pass on the affected gene to his daughters. A son cannot inherit the defective gene from his father. Genetic testing and genetic counselling is recommended for families with haemophilia. Prenatal testing, such as amniocentesis, is available to pregnant women who may be carriers of the condition.As with all genetic disorders, it is also possible for a human to acquire it spontaneously through mutation, rather than inheriting it, because of a new mutation in one of their parents gametes. Spontaneous mutations account for about 33% of all cases of haemophilia A. About 30% of cases of haemophilia B are the result of a spontaneous gene mutation.
If a female gives birth to a haemophiliac son, either the female is a carrier for the blood disorder or the haemophilia was the result of a spontaneous mutation. Until modern direct DNA testing, however, it was impossible to determine if a female with only healthy children was a carrier or not.If a male has the disease and has children with a female who is not a carrier, his daughters will be carriers of haemophilia. His sons, however, will not be affected with the disease. The disease is X-linked and the father cannot pass haemophilia through the Y-chromosome. Males with the disorder are then no more likely to pass on the gene to their children than carrier females, though all daughters they sire will be carriers and all sons they father will not have haemophilia (unless the mother is a carrier).

Severity
There are numerous different mutations which cause each type of haemophilia. Due to differences in changes to the genes involved, people with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those with 1–5% active factor have moderate haemophilia, and those with mild haemophilia have between 5% and 40% of normal levels of active clotting factor.

Diagnosis
Haemophilia can be diagnosed before, during or after birth if there is a family history of the condition. Several options are available to parents. If there is no family history of haemophilia, it is usually only diagnosed when a child begins to walk or crawl. They may experience joint bleeds or easy bruising.Mild haemophilia may only be discovered later, usually after an injury or a dental or surgical procedure.

Before pregnancy
Genetic testing and counselling are available to help determine the risk of passing the condition onto a child. This may involve testing a sample of tissue or blood to look for signs of the genetic mutation that causes haemophilia.

During pregnancy
A pregnant woman with a history of haemophilia in her family can test for the haemophilia gene. Such tests include:

chorionic villus sampling (CVS): a small sample of the placenta is removed from the womb and tested for the haemophilia gene, usually during weeks 11–14 of pregnancy
amniocentesis: a sample of amniotic fluid is taken for testing, usually during weeks 15–20 of pregnancyThere is a small risk of these procedures causing problems such as miscarriage or premature labour, so the woman may discuss this with the doctor in charge of her care.

After birth
If haemophilia is suspected after a child has been born, a blood test can usually confirm the diagnosis. Blood from the umbilical cord can be tested at birth if theres a family history of haemophilia. A blood test will also be able to identify whether a child has haemophilia A or B, and how severe it is.

Classification
There are several types of haemophilia: haemophilia A, haemophilia B, haemophilia C, parahaemophilia, acquired haemophilia A, and acquired haemophilia B.Haemophilia A is a recessive X-linked genetic disorder resulting in a deficiency of functional clotting Factor VIII. Haemophilia B is also a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX. Haemophilia C is an autosomal genetic disorder involving a lack of functional clotting Factor XI. Haemophilia C is not completely recessive, as heterozygous individuals also show increased bleeding.The type of haemophilia known as parahaemophilia is a mild and rare form and is due to a deficiency in factor V. This type can be inherited or acquired.A non-genetic form of haemophilia is caused by autoantibodies against factor VIII and so is known as acquired haemophilia A. It is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors. Acquired haemophilia can be associated with cancers, autoimmune disorders and following childbirth.

Management
There is no long-term cure. Treatment and prevention of bleeding episodes is done primarily by replacing the missing blood clotting factors.

Clotting factors
Clotting factors are usually not needed in mild haemophilia. In moderate haemophilia clotting factors are typically only needed when bleeding occurs or to prevent bleeding with certain events. In severe haemophilia preventive use is often recommended two or three times a week and may continue for life. Rapid treatment of bleeding episodes decreases damage to the body.Factor VIII is used in haemophilia A and factor IX in haemophilia B. Factor replacement can be either isolated from human blood serum, recombinant, or a combination of the two. Some people develop antibodies (inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as porcine factor VIII.If a person becomes refractory to replacement coagulation factor as a result of high levels of circulating inhibitors, this may be partially overcome with recombinant human factor VIII.In early 2008, the US Food and Drug Administration (FDA) approved an anti-haemophilic drug completely free of albumin, which made it the first anti-haemophilic drug in the US to use an entirely synthetic purification process. Since 1993 recombinant factor products (which are typically cultured in Chinese hamster ovary (CHO) tissue culture cells and involve little, if any human plasma products) have been available and have been widely used in wealthier western countries. While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world. In many cases, factor products of any sort are difficult to obtain in developing countries.Clotting factors are either given preventively or on-demand. Preventive use involves the infusion of clotting factor on a regular schedule in order to keep clotting levels sufficiently high to prevent spontaneous bleeding episodes. On-demand (or episodic) treatment involves treating bleeding episodes once they arise. In 2007, a trial comparing on-demand treatment of boys (< 30 months) with haemophilia A with prophylactic treatment (infusions of 25 IU/kg body weight of Factor VIII every other day) in respect to its effect on the prevention of joint-diseases. When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on MRI. Preventative treatment, however, resulted in average costs of $300,000 per year. The author of an editorial published in the same issue of the NEJM supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related haemorrhage may be more cost effective than waiting until the fixed age to begin. Most haemophiliacs in third world countries have limited or no access to commercial blood clotting factor products.

Other
Desmopressin (DDAVP) may be used in those with mild haemophilia A. Tranexamic acid or epsilon aminocaproic acid may be given along with clotting factors to prevent breakdown of clots.Pain medicines, steroids, and physical therapy may be used to reduce pain and swelling in an affected joint. In those with severe hemophilia A already receiving FVIII, emicizumab may provide some benefit. Different treatments are used to help those with an acquired form of hemophilia in addition to the normal clotting factors. Often the most effective treatment is corticosteroids which remove the auto-antibodies in half of people. As a secondary route of treatment, cyclophosphamide and cyclosporine are used and are proven effective for those who did not respond to the steroid treatments. In rare cases a third route or treatment is used, high doses of intravenous immunoglobulin or immunosorbent that works to help control bleeding instead of battling the auto-antibodies.

Contraindications
Anticoagulants such as heparin and warfarin are contraindicated for people with haemophilia as these can aggravate clotting difficulties. Also contraindicated are those drugs which have "blood thinning" side effects. For instance, medicines which contain aspirin, ibuprofen, or naproxen sodium should not be taken because they are well known to have the side effect of prolonged bleeding.Also contraindicated are activities with a high likelihood of trauma, such as motorcycling and skateboarding. Popular sports with very high rates of physical contact and injuries such as American football, hockey, boxing, wrestling, and rugby should be avoided by people with haemophilia. Other active sports like soccer, baseball, and basketball also have a high rate of injuries, but have overall less contact and should be undertaken cautiously and only in consultation with a doctor.

Prognosis
Like most aspects of the disorder, life expectancy varies with severity and adequate treatment. People with severe haemophilia who do not receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years. By the 1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years. Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from haemorrhage to HIV/AIDS acquired through treatment with contaminated blood products. The second leading cause of death related to severe haemophilia complications is intracranial haemorrhage which today accounts for one third of all deaths of people with haemophilia. Two other major causes of death include hepatitis infections causing cirrhosis and obstruction of air or blood flow due to soft tissue haemorrhage.

Epidemiology
Haemophilia frequency is about 1 instance in every 10,000 births (or 1 in 5,000 male births) for haemophilia A and 1 in 50,000 births for haemophilia B. About 18,000 people in the United States have haemophilia. Each year in the US, about 400 babies are born with the disorder. Haemophilia usually occurs in males and less often in females. It is estimated that about 2,500 Canadians have haemophilia A, and about 500 Canadians have haemophilia B.

History
Scientific discovery
The excessive bleeding was known to ancient people. The Talmud instructs that a boy must not be circumcised if he had two brothers who died due to complications arising from their circumcisions, and Maimonides says that this excluded paternal half-brothers. This may have been due to a concern about hemophilia. The first medical professional to describe the disease was Arab surgeon Al-Zahrawi, also known as Abulcasis. In the tenth century he described families whose males died of bleeding after only minor traumas. While many other such descriptive and practical references to the disease appear throughout historical writings, scientific analysis did not begin until the start of the nineteenth century.In 1803, John Conrad Otto, a Philadelphian physician, wrote an account about "a hemorrhagic disposition existing in certain families" in which he called the affected males "bleeders". He recognised that the disorder was hereditary and that it affected mostly males and was passed down by healthy females. His paper was the second paper to describe important characteristics of an X-linked genetic disorder (the first paper being a description of colour blindness by John Dalton who studied his own family). Otto was able to trace the disease back to a woman who settled near Plymouth, New Hampshire, in 1720. The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John F. Hay, published an account in The New England Journal of Medicine.In 1924, a Finnish doctor discovered a hereditary bleeding disorder similar to haemophilia localised in Åland, southwest of Finland. This bleeding disorder is called "Von Willebrand Disease".
The term "haemophilia" is derived from the term "haemorrhaphilia" which was used in a description of the condition written by Friedrich Hopff in 1828, while he was a student at the University of Zurich. In 1937, Patek and Taylor, two doctors from Harvard, discovered anti-haemophilic globulin. In 1947, Pavlosky, a doctor from Buenos Aires, found haemophilia A and haemophilia B to be separate diseases by doing a lab test. This test was done by transferring the blood of one haemophiliac to another haemophiliac. The fact that this corrected the clotting problem showed that there was more than one form of haemophilia.

European royalty
Haemophilia has featured prominently in European royalty and thus is sometimes known as the royal disease. Queen Victoria passed the mutation for haemophilia B to her son Leopold and, through two of her daughters, Alice and Beatrice, to various royals across the continent, including the royal families of Spain, Germany, and Russia. In Russia, Tsarevich Alexei, the son and heir of Tsar Nicholas II, famously had haemophilia, which he had inherited from his mother, Empress Alexandra, one of Queen Victorias granddaughters. The haemophilia of Alexei would result in the rise to prominence of the Russian mystic Grigori Rasputin, at the imperial court.It was claimed that Rasputin was successful at treating Tsarevich Alexeis haemophilia. At the time, a common treatment administered by professional doctors was to use aspirin, which worsened rather than lessened the problem. It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Tsarevich Alexei.In Spain, Queen Victorias youngest daughter, Princess Beatrice, had a daughter Victoria Eugenie of Battenberg, who later became Queen of Spain </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Ulegyria and explain in detail? [/INST] Ulegyria is a diagnosis used to describe a specific type of cortical scarring in the deep regions of the sulcus that leads to distortion of the gyri. Ulegyria is identified by its characteristic "mushroom-shaped" gyri, in which scarring causes shrinkage and atrophy in the deep sulcal regions while the surface gyri are spared. This condition is most often caused by hypoxic-ischemic brain injury in the perinatal period. The effects of ulegyria can range in severity, although it is most commonly associated with cerebral palsy, mental retardation and epilepsy. N.C. Bresler was the first to view ulegyria in 1899 and described this abnormal morphology in the brain as “mushroom-gyri." Although ulegyria was first identified in 1899, there is still limited information known or reported about the condition.

Anatomy
The physical features of ulegyria consist of small radial scars which occupy the cortical sulci. Overall, the physical structure of affected areas in the brain is described as a “mushroom”-like shape in which the gyri are unusually large and the sulci become wider deeper in the cortex. N.C. Bresler, the first person to view a brain with ulegyria in 1899, coined the phrase mushroom gyri. He also named the disorder, basing it off the Latin root ule, meaning scar. This mushroom-like structure is the result of the lower parts of the ulegyria-affected area being more prone to deterioration, while the upper gyri are usually spared. However, the entire affected area shrinks and presents brown coloration as a result of ulegyria. In addition, “islands” of neurons that are relatively unaffected can exist between ulegyria affected neurons. Ulegyria can develop bilaterally or unilaterally, though the former is more commonly diagnosed.Ulegyria can affect many parts of the brain including the cerebral cortex, parasagittal areas and posterior regions of the brain, such as the parietal and occipital lobes. These areas are situated either near artery rich regions or near a major cerebral artery. For instance, specifically in neonatal children, ulegyria-affected areas are found near the posterior cerebral artery or near the artery rich region between the middle and posterior regions of the brain, often referred to as watershed regions.Neurons affected by ulegyria exhibit properties that differ from normally functioning neurons. For instance, ulegyria affected neurons experience gliosis in which glial cells, specifically astrocytes, build up near and around neurons. Ulegyria affected neurons also display decreases in their white matter content, showing signs of sclerosis, which is characterized by the deterioration of myelin in neurons. However, in regions of grey matter, large dense aggregates of myelin are present.  Ulegyria affected neurons also display metabolic disorders which could be linked to the disease phenylketonuria and disruptions in the urea cycle. Hypoglycemia and  hypoxia are also thought to accompany the symptoms of ulegyria-affected neurons as well.

Causes
Ulegyria develops as a result of a brain injury called cerebral ischemia surrounding the time of an infants birth. Oftentimes, fetal hypoxic-ischemic brain injuries occur as a result of a pregnancy complications such as placental abruption, cord accident, or cardiovascular stress due to a difficult delivery. A lack of oxygen to the brain contributes to the formation of lesions usually near the three main cerebral arteries, located near the parietal lobe and occipital lobes of the brain. The cause of perinatal brain injuries includes:

1. cerebral ischemia
2. cerebral hemorrhage
3. ascending intrauterine infections.Some risk factors for perinatal brain injuries include: low birth weight, preterm birth, poor perinatal cardiorespiratory fitness, and artificial ventilation.

Cerebral ischemia
Cerebral ischemia occurs when the brain is not receiving adequate oxygen to continue normal functions. When this occurs, the body makes restoring oxygenated blood flow to life-sustaining organs a priority. The brain alters the diameter of major blood vessels to redistribute blood to key organs such as the brain, heart, and adrenal glands. If sympathetic nervous system activation does not produce any improvement, oxygen levels will continue to fall and disruptions to metabolism, other cellular processes, and overall functioning will ensue.
Another serious result of inefficient blood flow is that cells do not receive adequate amounts of glucose. An immediate effect of low intracellular glucose is reduced ATP production in the cell. This effectively inactivates the Na-K pump, leading to the uptake of calcium ions by the cell. Continued influx of calcium serves to constitutively activate downstream effectors, including lipases, proteases, and endonucleases, whose actions eventually destroy the cell skeleton. Intracellular calcium concentrations are increased further due to the opening of glutamate-regulated ion channels. Ischemia causes anoxic cell depolarizations and it is this increase in membrane potential at the presynaptic cell that triggers the release of glutamate, an excitatory neurotransmitter.Glucose deprivation in the brain for any amount of time has the potential to pose serious consequences, and the amount of time the brain spends under these anoxic conditions is directly related to accumulation of irreversible damage to protein biosynthesis pathways. Protein synthesis all over the body is severely inhibited and essentially comes to a standstill while the brain is suffering from acute oxygen deprivation. Once oxygen sufficiently saturates the tissues again, protein biosynthesis returns to normal in non-vulnerable areas but remains at below normal levels in other areas. Insufficient protein synthesis in the brain is especially troubling in the fetal brain given the amount of growth and development that normally occurs. Areas particularly vulnerable to the damaging effects of hypoxic episodes include: the superior brainstem, the cerebellum, white matter and subcortical structures supplied by the branches of deep and superficial penetrating blood vessels. Vulnerable areas where protein synthesis is interrupted usually indicate impending cell death in neurons. When oxygen levels return, oxygen radicals, nitric oxide and an imbalance of neurotransmitters cause further damage and lead to cellular death through apoptosis. Neuron cell death is responsible for gliosis and results in the mushroom appearance of areas and is characteristic of ulegyria.

Cerebral hemorrhage
A cerebral hemorrhage is the result of immature blood vessels of a brain lesion bursting. The germinal matrix is a part of the brain that normally disappears as the fetal brain develops but during this process it is not unusual for changes in vessel volume to cause a vessel to burst. According to recent microscopic studies, the most common location for a cerebral hemorrhage is where the medullary veins drain to the terminal vein in the sub-ependymal region. It has been hypothesized that because pre-term babies dont have fully developed sympathetic nervous systems, they cannot react as well to low oxygen saturation levels caused by the cerebral hemorrhage. Although babies born at full-term are still susceptible to this, they are likely to respond better and thus, tend to have better outcomes in response to low-oxygen events.

Ascending intrauterine infections
Recent research has found a connection between intrauterine infections and inflammation in the mother and an increased likelihood of perinatal brain damage in the fetus. This study suggested that intrauterine infections in the mother could affect glial cells and toll-like receptors (TLRs) which are important in moderating the inflammatory response in the fetal brain. When glial cells and TLRs are negatively affected they are not able to react to developing inflammation in the brain as well. The connection between ascending intrauterine infections and perinatal brain damage is a developing research theory but a more detailed explanation of the connection is not yet known.

Signs and symptoms
Ulegyria was found in about 1/3 of patients with defects caused by circulatory disease in the perinatal period. Most clinical observations of the condition report mental retardation, cerebral palsy, and seizures as the main defects. However, milder cases have been reported in which patients that exhibit ulegyria develop relatively normally. The main movement disorders associated with ulegyria that are classified as cerebral palsy are choreoathetosis, dystonia, and ataxia. It is suspected that ulegyria leads to epilepsy because malformation of the cortex obstructs the differentiation of neurons, glial cells, and synapses. Parietal-occipital lobe epilepsy, which is often synonymous with posterior cortex epilepsy (PCE), is the form of the disease seen in most cases involving ulegyria. This type of epilepsy is very rare, making up about 5% of all reports of epilepsy. This form of the disease involves symptoms that would be expected from damage to the parietal and occipital lobes: seizures with visual hallucinations, visuospatial dysfunction, tingling, numbness, pain, and a burning sensation. In addition to ulegyria, tumors and cortical dysplasia constitute the major causes of PCE. Most of the epilepsy seen in conjunction with ulegyria is classified as medically refractory, meaning it is not responsive to treatment. Patients usually present symptoms of epilepsy at an early age. The severity of epilepsy has been shown to depend on this age of onset as well as the quantity of cortical lesions; earlier onset of epilepsy and a larger extent of lesions tends to mean more severe seizures.

Similar conditions
Ulegyria is often confused with a similar distortion of the cortex known as polymicrogyria. Polymicrogyria is characterized by excessive folding of the surface gyri and a thickening of the cerebral cortex, rather than the sulcal scarring that is typical of ulegyria. In addition to morphological differences, the period in which polmicrogyria and ulegyria emerge is also different. Polymicrogyria typically forms while the embryos central nervous system is maturing. Ulegyria is acquired later in development during the perinatal period after neuronal migration has already occurred. It is also suspected that polymicrogyra is genetically linked, whereas ulegyria is caused by environmental factors—namely lack of oxygen.Polymicrogyria can lead to similar conditions that are linked to ulegyria such as mental retardation, cerebral palsy, and epilepsy. It has been observed that patients with polymicrogyria are not receptive to epilepsy surgery. However, responses of patients with ulegyria to similar surgeries are still not fully known, which makes distinction of these two disorders significant. In vivo neuroimaging techniques, namely MRI, have been instrumental in making this distinction. An MRI image of ulegyria is identified by mushroom shaped gyri, deformities in white matter, and localization mainly in the posterior cerebral region. Polymicrogyria is typically recognized by a scalloped appearance at the bordering region between grey and white matter. Although these distinctions have been made with many patients, there is still some difficulty in defining distinct boundaries between these two similar conditions.

Detection
Primarily, the main method of detecting ulegyria is through the use of MRI screening for epilepsy. Normally an MRI of an ulegyria affected region will reveal groups of deteriorated neurons with gliosis present. In addition, unaffected gyri are also present in especially bilateral watershed regions indicating delayed effects of perinatal hypoxic damage. However, there are three main criteria for diagnosing ulegyria using MRI in addition to the features mentioned above:
1.The presence of a poorly demarcated lesion
2. Atrophy and thinning of the cortex resulting in the characteristic “mushroom” like shape of ulegyria.
3. Presence of white matter signal abnormalities as a result of FLAIR signaling (fluid attenuated inversion recovery).Another sign of ulegyria that is visible on an MRI scan is the presence of a widened subarachnoid space, signifying cortex atrophy. FLAIR signaling can help visualize the depths of the parietal-occipital sulci, which also allows ulegyria-affected gyri to be identified </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hypogonadotropic hypogonadism and explain in detail? [/INST] Hypogonadotropic hypogonadism (HH),  is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis).  Hypothalamic disorders result from a deficiency in the release of gonadotropic releasing hormone (GnRH), while pituitary gland disorders are due to a deficiency in the release of gonadotropins from the anterior pituitary. GnRH is the central regulator in reproductive function and sexual development via the HPG axis. GnRH is released by GnRH neurons, which are hypothalamic neuroendocrine cells, into the hypophyseal portal system acting on gonadotrophs in the anterior pituitary.
The release of gonadotropins, LH and FSH, act on the gonads for the development and maintenance of proper adult reproductive physiology. LH acts on Leydig cells in the male testes and theca cells in the female. FSH acts on Sertoli cells in the male and follicular cells in the female. Combined this causes the secretion of gonadal sex steroids and the initiation of folliculogenesis and spermatogenesis. The production of sex steroids forms a negative feedback loop acting on both the anterior pituitary and hypothalamus causing a pulsatile secretion of GnRH.
GnRH neurons lack sex steroid receptors and mediators such as kisspeptin stimulate GnRH neurons for pulsatile secretion of GnRH.

Types
There are two subtypes of HH, congenital HH (CHH) and acquired HH (AHH). CHH is due to genetic abnormalities resulting in non-functional GnRH secreting neurons or gonadotropic cell dysfunction in the anterior pituitary. CHH is divided into 2 subtypes depending on the condition of the olfactory system, anosmic HH (Kallman syndrome) and normosmic HH.
AHH is an acquired form of the disease often occurring after sexual maturation and is not related to genetic defects.

Pathogenesis
CHH is a type of HH resulting from the abnormal migration of GnRH neurons during embryonic development. GnRH neurons are derived from the olfactory placode and migrate into the central nervous system (CNS) during embryonic development. Embryonic migration can be affected by several gene mutations including but not limited to, KAL1, fibroblast growth factor (FGF8), sex determining region Y-Box 10 (SOX10), GNRHR, GNRH1 and KISS1R.  Kallmann syndrome results in a loss of smell (anosmia) and is associated with KAL1 mutations. The KAL1 gene encodes anosmin-1, an extracellular adhesion molecule that plays a role in GnRH neuronal migration and adhesion.
Mutated KAL1 genes leads to ill GnRH neuronal migration as well as olfactory neuron disorder causing anosmia and non-functional GnRH releasing neurons. Mutations of KAL1 are mostly nucleotide insertion or deletion causing frame shifts in the translation of anosmin-1 resulting in a faulty protein.
Inactivating mutations in the genes encoding GNRH1 or its receptor will result in the failure of the HPG axis and give rise to normosmic CHH.
Inactivating mutations of KISS1 or KISS1R causes normosmic CHH in humans.
This is because KISS1 is the mediator for the feedback loop in the HPG axis allowing low levels of sex steroid to stimulate GnRH secretion from the hypothalamus.CHH is a genetically heterogenous disorder with cases reported as being X-linked, recessive and autosomally inherited.
The prevalence has been estimated to be 1/4000 to 1/10000 in males and 2 to 5 times less frequent in females. The prevalence difference between male and females is unknown, and is likely to be underreported for females.Acquired hypogonadotropic hypogonadism (AHH) is a postnatal onset of a GnRH releasing disorder and/or pituitary gonadotroph cell disorder.
There are many causes of AHH, mostly due to structural or functional abnormalities involving the HPG axis such as sarcoidosis, lymphocytic hypophysitis, pituitary adenomas, craniopharyngiomas and other CNS tumours. Most of these patients have multiple pituitary hormone deficiencies.  Hyperprolactinaemia is the most common cause of AHH. It is a well-established cause of infertility in both male and female mammals. Prolactin inhibits GnRH neurons and therefore inhibits the subsequent release of LH, FSH and sex steroids. The mechanism of prolactin induced inhibition of GnRH release is poorly understood.
It is suspected that the prolactin receptor is expressed on a small subset of GnRH neurons in mice and thus has a direct inhibitory effect on GnRH release. There is evidence to suggest indirect inhibition of GnRH neurons mediated by other neurotransmitters such as dopamine, opioid, neuropeptide Y and γ-aminobutyric acid.
Drug usage of glucocorticoids and opioid analgesics in high dosages can lead to the inhibition of GnRH synthesis.
Opioid receptors reside in the hypothalamus and when bound to opioids they decrease the normal pulsatile secretion of GnRH and therefore result in HH.
Chronic treatment with supraphysiological doses of glucocorticoids results in a marked decrease in testosterone without an increase of LH levels, suggestive of a central mechanism of induced HH.

Diagnosis
The clinical presentation of HH depend on the time of onset as well as the severity of the defect.
Diagnostic tests to measure GnRH levels are difficult. This is because GnRH is confined within hypophyseal portal system and has a short half-life of 2–4 minutes.
GnRH levels are thus checked indirectly via LH and FSH levels which will be totally or partially absent in HH. Exogenous GnRH can be used as a diagnostic tool. If the patient has hypothalamic GnRH deficiency, LH and FSH will gradually appear in response to the exogenous GnRH but in pituitary cases of HH, a minimal response will be generated.
Typically, CHH is diagnosed in adolescence due to a lack of pubertal development, but it can be possible to diagnose in male neonates. Clinical presentations of CHH involve an absence of puberty by 18 years of age, poorly developed secondary sexual characteristics, or infertility.In men with CHH, serum levels of inhibin B are typically very low as inhibin B is a marker of Sertoli cell number.
For females, CHH is most commonly revealed by primary amenorrhea. Breast development is variable and pubic hair may or may not be present.
CHH can be diagnosed in the male neonate with cryptorchidism (maldescended testes) and a micropenis as signs of GnRH deficiency.
There are no clear signs of CHH in female neonates.
Another clinical sign of CHH, more specifically Kallmann syndrome, is a lack of a sense of smell due to the altered migration of GnRH neurons on the olfactory placode. Kallmann syndrome can also be shown through MRI imaging with irregular morphology or aplasia of the olfactory bulb and olfactory sulci </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pseudopseudohypoparathyroidism and explain in detail? [/INST] Pseudopseudohypoparathyroidism (PPHP) is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. It is more properly Albright hereditary osteodystrophy although without resistance of parathyroid hormone as frequently seen in that affliction. The term Pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of Pseudohypoparathyroidism type 1a, but has (unexpected for the phenotype) normal labs including calcium and PTH.It can be considered a variant of Albright hereditary osteodystrophy, or Pseudohypoparathyroidism type 1A, as they present with the same constellation of signs and symptoms, including short stature, brachydactyly, subcutaneous calcification, and obesity.

Presentation
Pseudopseudohypoparathyroidism can be best understood by comparing it to other conditions:

Hormone resistance is not present in Pseudopseudohypoparathyroidism. Short stature may be present. Obesity is less common in Pseudopseudohypoparathyroidism  than in Pseudohypoparathyroidism. Osteoma cutis may be present.

Genetics
A male with Pseudohypoparathyroidism has a 50% chance of passing on the defective GNAS gene to his children, although in an imprinted, inactive form. Any of his children receiving this gene will have Pseudopseudohypoparathyroidism </s>