<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Kleptomania and can you explain it in depth? [/INST] Kleptomania is the inability to resist the urge to steal items, usually for reasons other than personal use or financial gain. First described in 1816, kleptomania is classified in psychiatry as an impulse control disorder. Some of the main characteristics of the disorder suggest that kleptomania could be an obsessive-compulsive spectrum disorder, but also share similarities with addictive and mood disorders.The disorder is frequently under-diagnosed and is regularly associated with other psychiatric disorders, particularly anxiety, eating disorders, alcohol and substance use. Patients with kleptomania are typically treated with therapies in other areas due to the comorbid grievances rather than issues directly related to kleptomania.Over the last 100 years, a shift from psychotherapeutic to psychopharmacological interventions for kleptomania has occurred. Pharmacological treatments using selective serotonin reuptake inhibitors (SSRIs), mood stabilizers and opioid receptor antagonists, and other antidepressants along with cognitive behavioral therapy, have yielded positive results. However, there have also been reports of kleptomania induced by selective serotonin reuptake inhibitors (SSRIs).

Signs and symptoms
Some of the fundamental components of kleptomania include recurring intrusive thoughts, impotence to resist the compulsion to engage in stealing, and the release of internal pressure following the act. These symptoms suggest that kleptomania could be regarded as an obsessive-compulsive type of disorder.People diagnosed with kleptomania often have other types of disorders involving mood, anxiety, eating, impulse control, and drug use. They also have great levels of stress, guilt, and remorse, and privacy issues accompanying the act of stealing. These signs are considered to either cause or intensify general comorbid disorders. The characteristics of the behaviors associated with stealing could result in other problems as well, which include social segregation and substance use. The many types of other disorders frequently occurring along with kleptomania usually make clinical diagnosis uncertain.There is a difference between ordinary theft and kleptomania: "ordinary theft (whether planned or impulsive) is deliberate and motivated by the usefulness of the object or its monetary worth," whereas with kleptomania, there "is the recurrent failure to resist impulses to steal items even though the items are not needed for personal use or for their monetary value."

Cause
Psychoanalytic models
Many psychoanalytic theorists suggested  that kleptomania is a persons attempt "to obtain symbolic compensation for an actual or anticipated loss", and feel that the key to understanding its etiology lies in the symbolic meaning of the stolen items. Drive theory was used to propose that the act of stealing is a defense mechanism which serves as to modulate or keep undesirable feelings or emotions from being expressed. Some French psychiatrists suggest that kleptomaniacs may just want the item that they steal and the feeling they get from  theft itself.

Cognitive-behavioral models
Cognitive-behavioral models have been replacing psychoanalytic models in describing the development of kleptomania. Cognitive-behavioral practitioners often conceptualize the disorders as being the result of operant conditioning, behavioral chaining, distorted cognitions, and poor coping mechanisms. Cognitive-behavioral models suggest that the behavior is positively reinforced after the person steals some items. If this individual experiences minimal or no negative consequences (punishment), then the likelihood that the behavior will reoccur is increased. As the behavior continues to occur, stronger antecedents or cues become contingently linked with it, in what ultimately becomes a powerful behavioral chain. According to cognitive-behavioral theory (CBT), both antecedents and consequences may either be in the environment or cognitions. For example, Kohn and Antonuccio (2002) describe a clients antecedent cognitions, which include thoughts such as "I’m smarter than others and can get away with it"; "they deserve it"; "I want to prove to myself that I can do it"; and "my family deserves to have better things". These thoughts were strong cues to stealing behaviors. All of these thoughts were precipitated by additional antecedents which were thoughts about family, financial, and work stressors or feelings of depression. "Maintaining" cognitions provided additional reinforcement for stealing behaviors and included feelings of vindication and pride, for example: "score one for the little guy against the big corporations". Although those thoughts were often afterward accompanied by feelings of remorse, this came too late in the operant sequence to serve as a viable punisher. Eventually, individuals with kleptomania come to rely upon stealing as a way of coping with stressful situations and distressing feelings, which serve to further maintain the behavior and decrease the number of available alternative coping strategies.

Biological models
Biological models explaining the origins of kleptomania have been based mostly on pharmacotherapy treatment studies that used selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and opioid receptor antagonists.Some studies using SSRIs have observed that opioid antagonists appear to reduce the urge to steal and mute the "rush" typically experienced immediately after stealing by some subjects with kleptomania. This would suggest that poor regulation of serotonin, dopamine, and/or natural opioids within the brain are to blame for kleptomania, linking it with impulse control and affective disorders.An alternative explanation too based on opioid antagonist studies states that kleptomania is similar to the "self-medication" model, in which stealing stimulates the persons natural opioid system. "The opioid release soothes the patients, treats their sadness, or reduces their anxiety. Thus, stealing is a mechanism to relieve oneself from a chronic state of hyperarousal, perhaps produced by prior stressful or traumatic events, and thereby modulate affective states.": 354

Diagnosis
Disagreement surrounds the method by which kleptomania is considered and diagnosed. On one hand, some researchers believe that kleptomania is merely theft and dispute the suggestion that there are psychological mechanisms involved, while others observe kleptomania as part of a substance-related addiction. Yet others categorize kleptomania as a variation of an impulse control disorder, such as obsessive-compulsive disorder or eating disorders.: 378–84 According to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM IV-TR), a frequent and widely used guide for the diagnosis of mental disorders, the following symptoms and characteristics are the diagnostic criteria for kleptomania:

repeated inability to defend against urges to steal things that are not essential for private use or for their economic value;
escalating sense of pressure immediately prior to performing the theft;
satisfaction, fulfillment or relief at the point of performing the theft;
the theft is not executed to convey antagonism or revenge, and is not in reaction to a delusion or a fantasy; and
the thieving is not better accounted for by behavior disorder, a manic episode, or antisocial personality disorder.Skeptics have decried kleptomania as an invalid psychiatric concept exploited in legal defenses of wealthy female shoplifters. During the twentieth century, kleptomania was strongly linked with the increased prevalence of department stores, and "department store kleptomaniacs" were a widely held social stereotype that had political implications.

Comorbidity
Kleptomania seems to be linked with other psychiatric disorders, especially mood swings, anxiety, eating disorders, and alcohol and substance use. The occurrence of stealing as a behavior in conjunction with eating disorders, particularly bulimia nervosa, is frequently taken as a sign of the harshness of the eating disorder.A likely connection between depression and kleptomania was reported as early as 1911. It has since been extensively established in clinical observations and available case reports. The mood disorder could come first or co-occur with the beginning of kleptomania. In advanced cases, depression may result in self-inflicted injury and could even lead to suicide. Some people have reported relief from depression or manic symptoms after theft.It has been suggested that because kleptomania is linked to strong compulsive and impulsive qualities, it can be viewed as a variation of obsessive-compulsive spectrum disorders, together with pathological gambling, compulsive buying, pyromania, nailbiting and trichotillomania. This point achieves support from the unusually higher cases of obsessive-compulsive disorder (OCD; see below) in close relatives of patients with kleptomania.

Substance use disorder
Kleptomania and drug addictions seem to have central qualities in common, including:

recurring or compulsive participation in a behavior in spite of undesirable penalties;
weakened control over the disturbing behavior;
a need or desire condition before taking part in the problematic behavior; and
a positive pleasure-seeking condition throughout the act of the disturbing behavior.Data from epidemiological studies additionally propose that there is an affiliation between kleptomania and substance use disorders along with high rates in a unidirectional manner. Phenomenological data maintain that there is a relationship between kleptomania and drug addictions. A higher percentage of cases of kleptomania has been noted in adolescents and young adults, and a lesser number of cases among older adults, which imply an analogous natural history to that seen in substance use disorders. Family history data also propose a probable common genetic input to alcohol use and kleptomania. Substance use disorders are more common in kin of persons with kleptomania than in the general population. Furthermore, pharmacological data (e.g., the probable efficacy of the opioid antagonist, naltrexone, in the treatment of both kleptomania and substance use disorders) could present additional support for a joint relationship between kleptomania and substance use disorders. Based on the idea that kleptomania and substance use disorders may share some etiological features, it could be concluded that kleptomania would react optimistically to the same treatments. As a matter of fact, certain non-medical treatment methods that are successful in treating substance use are also accommodating in treating kleptomania.

Obsessive-compulsive disorder
Kleptomania is frequently thought of as being a part of obsessive-compulsive disorder (OCD), since the irresistible and uncontrollable actions are similar to the frequently excessive, unnecessary, and unwanted rituals of OCD. Some individuals with kleptomania demonstrate hoarding symptoms that resemble those with OCD.
Prevalence rates between the two disorders do not demonstrate a strong relationship. Studies examining the comorbidity of OCD in subjects with kleptomania have inconsistent results, with some showing a relatively high co-occurrence (45%-60%) while others demonstrate low rates (0%-6.5%). Similarly, when rates of kleptomania have been examined in subjects with OCD, a relatively low co-occurrence was found (2.2%-5.9%).

Pyromania
Pyromania, another impulse disorder, has many ties to kleptomania. Many pyromaniacs begin fires alongside petty stealing which often appears similar to kleptomania.

Treatment
Although the disorder has been known to psychologists for a long time, the cause of kleptomania is still ambiguous. Therefore, a diverse range of therapeutic approaches have been introduced for its treatment. These treatments include: psychoanalytic oriented psychotherapy, behavioral therapy, and pharmacotherapy.

Psychoanalytic and psychodynamic approach
Several explanations of the mechanics of kleptomania have been presented. A contemporary social approach proposes that kleptomania is an outcome of consumerism and the large quantity of commodities in society. Psychodynamic theories depend on a variety of points of view in defining the disorder. Psychoanalysts define the condition as an indication of a defense mechanism deriving in the unconscious ego against anxiety, prohibited intuition or desires, unsettled struggle or forbidden sexual drives, dread of castration, sexual excitement, and sexual fulfillment and orgasm throughout the act of stealing. The psychoanalytic and psycho-dynamic approach to kleptomania granted the basis for prolonged psychoanalytic or psycho-dynamic psychotherapy as the core treatment method for a number of years. Like most psychiatric conditions, kleptomania was observed within the psycho-dynamic lens instead of being viewed as a bio-medical disorder. However, the prevalence of psychoanalytic approach contributed to the growth of other approaches, particularly in the biological domain.

Behavioral and cognitive intervention
Cognitive-behavioural therapy (CBT) has primarily substituted the psychoanalytic and dynamic approach in the treatment of kleptomania. Numerous behavioural approaches have been recommended as helpful according to several cases stated in the literature. They include: hidden sensitisation by unpleasant images of nausea and vomiting, aversion therapy (for example, aversive holding of breath to achieve a slightly painful feeling every time a desire to steal or the act is imagined), and systematic desensitisation. In certain instances, the use of combining several methods such as hidden sensitisation along with exposure and response prevention were applied. Even though the approaches used in CBT need more research and investigation in kleptomania, success in combining these methods with medication was illustrated over the use of drug treatment as the single method of treatment.

Drug treatment
The phenomenological similarity and the suggested common basic biological dynamics of kleptomania and OCD, pathological gambling and trichotillomania gave rise to the theory that the similar groups of medications could be used in all these conditions. Consequently, the primary use of selective serotonin reuptake inhibitor (SSRI) group, which is a form of antidepressant, has been used in kleptomania and other impulse control disorders such as binge eating and OCD. Electroconvulsive therapy (ECT), lithium and valproic acid (sodium valproate) have been used as well.The SSRIs usage is due to the assumption that the biological dynamics of these conditions derives from low levels of serotonin in brain synapses, and that the efficacy of this type of therapy will be relevant to kleptomania and to other comorbid conditions.Opioid receptor antagonists are regarded as practical in lessening urge-related symptoms, which is a central part of impulse control disorders; for this reason, they are used in treatment of substance use. This quality makes them helpful in treating kleptomania and impulse control disorders in general. The most frequently used drug is naltrexone, a long-acting competitive antagonist. Naltrexone acts mainly at μ-receptors, but also antagonises κ- and λ-receptors.There have been no controlled studies of the psycho-pharmacological treatment of kleptomania. This could be as a consequence of kleptomania being a rare phenomenon and the difficulty in achieving a large enough sample. Facts about this issue come largely from case reports or from bits and pieces gathered from a comparatively small number of cases enclosed in a group series.

History
In the nineteenth century, French psychiatrists began to observe kleptomaniacal behavior, but were constrained by their approach. By 1890, a large body of case material on kleptomania had been developed </s>


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


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tangier disease and can you explain it in depth? [/INST] Tangier disease  or hypoalphalipoproteinemia is an extremely rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein (HDL), often referred to as "good cholesterol", in the bloodstream.  Worldwide, approximately 100 cases have even been identified.The disorder was originally discovered on Tangier Island off the coast of Virginia, but has now been identified in people from many different countries.

Signs and symptoms
Individuals that are homozygotes for Tangiers disease develop various cholesterol ester depositions. These are especially visible in the tonsils, as they may appear yellow/orange. The cholesterol esters may also be found in lymph nodes, bone marrow, the liver and spleen.Due to the cholesterol ester depositions the tonsils may be enlarged. Hepatosplenomegaly (enlarged liver and spleen) is common.Neuropathy and cardiovascular disease are the most devastating developments caused by Tangiers disease.

Genetics
Mutations to chromosome 9q31 lead to a defective ABCA1 transporter. These mutations prevent the ABCA1 protein from effectively transporting cholesterol and phospholipids out of cells for pickup by ApoA1 in the bloodstream. This inability to transport cholesterol out of cells leads to a deficiency of high-density lipoproteins in the circulation, which is a risk factor for coronary artery disease. Additionally, the buildup of cholesterol in cells can be toxic, causing cell death or impaired function. These combined factors lead to the signs and symptoms of Tangier disease.This condition is inherited in an autosomal recessive pattern, meaning that for the phenotype to appear, two copies of the gene must be present in the genotype. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

Diagnosis
Tangier disease results in familial high-density lipoprotein deficiency. High-density lipoproteins are created when a protein in the bloodstream, Apolipoprotein A1 (apoA1), combines with cholesterol and phospholipids. The cholesterol and phospholipids used to form HDL originate from inside cells but are transported out of the cell into the blood via the ABCA1 transporter. People with Tangier disease have defective ABCA1 transporters resulting in a greatly reduced ability to transport cholesterol out of their cells, which leads to an accumulation of cholesterol and phospholipids in many body tissues, which can cause them to increase in size. Reduced blood levels of high-density lipoproteins is sometimes described as hypoalphalipoproteinemia.People affected by this condition also have slightly elevated amounts of fat in the blood (mild hypertriglyceridemia) and disturbances in nerve function (neuropathy). The tonsils are visibly affected by this disorder; they frequently appear orange or yellow and are extremely enlarged. Affected people often develop premature atherosclerosis, which is characterized by fatty deposits and scar-like tissue lining the arteries </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Liver spot and can you explain it in depth? [/INST] Liver spots (also known as age spot, solar lentigo, "lentigo senilis",: 686  "old age spot", "senile freckle") are blemishes on the skin associated with aging and exposure to ultraviolet radiation from the sun. They range in color from light brown to red or black and are located in areas most often exposed to the sun, particularly the hands, face, shoulders, arms and forehead, and the scalp if bald.
The spots derive their name from the fact that they were once incorrectly believed to be caused by liver problems, but they are physiologically unrelated to the liver, save for a similar color. From the age of 40, the skin is less able to regenerate from sun exposure, and liver spots are very common in this age group, particularly in those who spend time in the sun.In the overwhelming majority of cases, liver spots pose no threat and require no treatment, though they occasionally have been known to obscure the detection of skin cancer. However, despite being a benign condition, liver spots are sometimes considered unsightly and some people choose to have them removed. This can be done by electrosurgery, laser treatment, cryotherapy, or the use of depigmentation agents, such as hydroquinone,  tretinoin, topical cysteamine, azelaic acid, or alpha hydroxy acids.

Causes
Differently from the melanotic nevi and the verrucous nevi on the skin, age spots change in color and in shape with time </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Nightmare disorder and can you explain it in depth? [/INST] Nightmare disorder, also known as dream anxiety disorder, is a sleep disorder characterized by frequent nightmares. The nightmares, which often portray the individual in a situation that jeopardizes their life or personal safety, usually occur during the REM stages of sleep. Though most people have experienced at least one nightmare during their life, subjects with nightmare disorder experience them with a greater frequency. The disorders DSM-IV number is 307.47.
Nightmare disorders are included in the group of parasomnias, which cover all unusual behaviours during sleep. Nightmare disorders can be confused with sleep terror disorders. The difference is that after a sleep terror episode, the patient wakes up with more dramatic symptoms than with a nightmare disorder, such as screaming and crying. Furthermore, they dont remember the reason of the fear, while a patient with a nightmare disorder remembers every detail of the dream. Finally, the sleep terrors usually occur during NREM Sleep.Nightmares also have to be distinguished from bad dreams, which are less emotionally intense. Furthermore, nightmares contain more scenes of aggression than bad dreams and more unhappy endings. Finally, people experiencing nightmares feel more fear than with bad dreams.The treatment depends on whether or not there is a comorbid PTSD diagnosis. About 4% of American adults are affected.

Signs and symptoms
During the nightmare, the sleeper may scream and yell out things. The nightmare sufferer is often awakened by these threatening, frightening dreams and can often vividly remember their experience. Upon awakening, the sleeper is usually alert and oriented within their surroundings, but may have an increased heart rate and symptoms of anxiety, like sweating. They may have trouble falling back to sleep for fear they will experience another nightmare.
A person experiencing nightmare disorder may have trouble going through everyday tasks; anxiety and lack of sleep caused by the fearful dreams may hinder the individual from completing everyday tasks efficiently and correctly. Upon experiencing this, these nightmare sufferers may consult with a psychiatrist.
The sleeper may have recurring episodes of awakening while recalling the intensely disturbing dream manifestations which usually result from fear or anxiety, but can also be triggered by anger, sadness, disgust, and other dysphoric emotions. Additionally, the sleeper may experience at least one of the following two features: delayed return of going back to sleep after episodes, and having episodes in the latter half of the sleep period.

Consequences
Nightmare disorder is common: it affects about 4% of the adult population. Even if children have more nightmares than adults, only 1% of children meet the criteria of the disorder. Nightmare disorder can impair the quality of life for people who are affected by the condition. It can make the patient avoid sleep, which leads to sleep deprivation, which in turn may lead to even more intense nightmares. Some other consequences of the nightmare disorder are fatigue and insomnia.Nightmare disorders have negative consequences on several aspects of the patients life, such as sleep, cognitive and emotional functioning and well-being. Nightmares can also have negative impact on the bed partners life.

Content of idiopathic nightmares
Physical aggression is the main theme of nightmares. Other fields, such as interpersonal conflict, failure, helplessness, apprehension, being chased, accidents, evil forces, disasters, insects and environmental abnormalities may also feature in nightmares. Fear is the most frequent emotion associated with nightmares, even if other emotions such as sadness, anger, and confusion can also be present.

Criteria
According to the International Classification of Sleep Disorders, the criteria needed to diagnose a nightmare disorder are the following. First, the presence of frequent nightmares that imply danger for the person and impact mood in a negative way is needed. Second, when waking up from nightmares, the person behaves in an alert way. Finally, the disorder has to have a significant impact on the patients personal, social or professional functioning, in areas like mood, sleep, cognition, behaviour, fatigue, family and occupation.

Causes
Nightmares can be caused by extreme pressure or irritation if no other mental disorder is discovered. The death of a loved one or a stressful life event can be enough to cause a nightmare but conditions such as post-traumatic stress disorder and other psychiatric disorders have been known to cause nightmares as well. If the individual is on medication, the nightmares may be attributed to some side effects of the drug. Amphetamines, antidepressants, and stimulants like cocaine and caffeine can cause nightmares. Blood pressure medication, levodopa and medications for Parkinsons disease have also been known to cause nightmares.The nightmares may be idiopathic or could be associated with psychiatric disorders like post-traumatic stress disorder, schizophrenia, and borderline personality disorder. Nightmares can also be triggered by stress and anxiety and substance abuse, such as drugs that affect the neurotransmitters norepinephrine and dopamine and serotonin. Nevertheless, causality between drugs such as beta-blockers or alpha-agonists and nightmares is still unclear and further research needs to be done to investigate the biochemical mechanisms of nightmares.Eighty percent of patients who have PTSD report nightmares. Patients with PTSD have symptoms that are classified into three clusters: intrusive/re-experiencing, numbing, and hyperarousal. Nightmares are usually considered to be part of the intrusive/re-experiencing symptom.Some differences are existing between idiopathic and PTSD related nightmares. A PTSD person having nightmares would wake up during the night more frequently and for a longer time than with idiopathic nightmares. Consequently, people with PTSD would have a poorer sleep quality. Furthermore, nightmares related to PTSD would be more stressful than idiopathic ones. However, further studies have to be conducted in this area to obtain more reliable results.

Assessment
Polysomnography records physiological parameters, such as electroencephalography (EEG), electromyography (EMG) and electrooculography (EOG) in a sleep laboratory. However, the frequency of posttraumatic nightmares tends to decrease in an artificial lab setting, which would impact the content of nightmares. Consequently, assessment of nightmare disorders using polysomnography has to last for a longer period, in order to let the patient getting used to the artificial environment.Self-report by a questionnaire or by a diary is another way to investigate nightmare disorders. However, these methods are questionable. Indeed, when filling out questionnaires with questions about a long period, people often tend to underestimate the frequency of their nightmares because of forgetting. On the contrary, filling out a diary every day may lead to an overestimation of the numbers of nightmares, because of the focusing on this phenomenon.

Comorbidity
Studies have reported that nightmare disorders were present in 50- 70% of the cases for PTSD, in 17.5% for depression, in 18.3% for insomnia, in 16.7% for schizophrenia and in 49% for borderline personality disorder. For all psychiatric disorders taken together, nightmare disorders are present in 29.9% of the cases, a much bigger rate than for the general population, which is 2-5%. Nightmare disorders can also be associated with sleep disorders such as night terrors, chronic insomnia and sleep-disordered breathing. The presence of nightmares before a trauma would influence severity of PTSD symptoms. Furthermore, having nightmares is linked to a significantly higher risk of attempting suicide and of death by suicide.

Treatment
Stress reduction techniques such as yoga, meditation and exercise may help to eliminate stress and create a more peaceful sleeping atmosphere.Diagnosis and medication can only be given to patients that report the recurring nightmares to a psychiatrist or other physician. Medications like prazosin are sometimes used to treat nightmares in people with PTSD. Therapy usually helps to deal with the frightening themes of the nightmares and alleviate the recurrence of the dreams. The persistent nightmares will usually improve as the patient gets older. Therapy is usually efficient to treat chronic nightmares in PTSD disorder or in other population. Medication has shown efficacy to treat chronic nightmares among a PTSD population but the impact of pharmacological treatments on other populations, such as drug-related nightmares, are unknown. Furthermore, patients usually take more than one medication at a time, whatever the cause related to nightmares, leading to possible interactive effects.Eye Movement Desensitization and Reprocessing (EMDR) has demonstrated a significant nightmares reduction, especially for the treatment of PTSD. Silver, Brooks and Obenchain have found a decrease of the nightmares with Vietnam War veterans after 90 days of EMDR. Jayatunge has found significant results with people who have survived to a tsunami. Greenwald has successfully used the EMDR with children. There wasnt any negative consequence due to the EMDR sessions.
Imagery rehearsal therapy has been shown as efficient to treat nightmare disorder in PTSD as well as in non PTSD populations. In this treatment, the person has to write a new scenario of the nightmare with positive images that will be rehearsed during 10 to 20 minutes per day, in order to change the negative content of the nightmare. Cognitive behavioral therapy for insomnia (CBT-I) is also efficient to treat nightmares in the PTSD population. This method aims to change sleep habits with a clinicians help and the use of tools such as a sleep diary.Exposure, relaxation and rescripting therapy is used to treat PTSD-related nightmares. This intervention combines Imagery Rehearsal Therapy with exposure and relaxation techniques. The main objective is to work on the trauma-related themes of nightmares.Research has been undertaken to investigate if sufferers of nightmares could benefit from the ability to be aware that they are indeed dreaming, a process known as lucid dreaming. The Lucid Dreaming Therapy is a specific method of the Imagery Rehearsal Therapy. The dreamer is conscious during his dream and can modulate it. Consequently, anxiety decreases, controllability increases, expectations change, which will impact the frequency of nightmares. Several studies have shown significant results with the lucid dreaming therapy. Two studies indicate a decrease of the nightmare frequency after only 12 weeks and one study shows, in 80% of the cases, a total disappearance of the nightmares after one year. Although these studies showed the efficacy of this therapy in the reduction of nightmare frequency on patients from the general population, so far evidence for this treatment is still weak.Systematic Desensitization, using graduated exposure, has been shown to be efficient to treat chronic nightmares. The person has to face the frightening elements of nightmares in a gradually way, from the less to the most stressful. When the person starts to feel unsecure, she has to manage the stress by applying a relaxation technique.

Pharmacological treatments
Pharmacological treatments could be also efficient to treat nightmare disorder. Most of the treatments were assessed to patients with PTSD. The most efficient is an alpha-blocker, Prazosin, which reduces tone during sleep by blocking noradrenergic receptors. Prazosin would significantly decrease the number of PTSD related nightmares and would therefore improve sleep quality. However, only few studies considered the effect of Prazosin in idiopathic nightmares. Benzodiazepines are also often used to treat nightmare disorder, despite the lack of efficacy demonstrated in empirical studies. Some patients were also treated with atypical antipsychotic medications. Olanzapine has quickly decreased the nightmares. Two studies have shown the positive effects of Risperidone. Aripiprazole is more tolerated than olanzapine and has demonstrated substantial improvement in the nightmare frequency. Some other drugs as clonidine, cyproheptadine, fluvoxamine, gabapentin, nabilone, phenelzine, topiramate or trazodone have presented an amelioration of the nightmares. But some further researches are needed.

Epidemiology
About 4% of American adults are affected by nightmare disorders. Women seem to be more affected than men, the ratio being 2-4 : 1 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Aquagenic pruritus and can you explain it in depth? [/INST] Aquagenic pruritus is a skin condition characterized by the development of severe, intense, prickling-like epidermal itching without observable skin lesions and evoked by contact with water.

Presentation
Presentation varies from person to person </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Severe congenital neutropenia and can you explain it in depth? [/INST] Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections.Most cases of SCN respond to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections. Although this treatment has significantly improved survival, people with SCN are at risk of long-term complications such as hematopoietic clonal disorders (myelodysplastic syndrome, acute myeloid leukemia).
Kostmann disease (SCN3), the initial subtype recognized, was clinically described in 1956. This type has an autosomal recessive inheritance pattern, whereas the most common subtype, SCN1, shows autosomal dominant inheritance.

Presentation
Infants with SCN have frequent infections: 50% have a significant infection within 1 month, most others by 6 months. Their etiology is usually bacterial, especially staphylococcal, and they commonly involve abscesses, both cutaneous and of internal organs, pneumonia, mastoiditis (inflammation of the mastoid process), and sepsis. All of these are life-threatening for infants.

Genetics
Kostmann disease, SCN3, is inherited in an autosomal recessive manner, but the commonest subtype of Kostmann syndrome, SCN1, is autosomal dominant.A significant proportion of SCN lacks a known mutation. The recognized subtypes of Kostmann syndrome are:

SCN1 is the commonest form of SCN, which accounts for 60-80% of SCN, and the first to be genetically typified. This autosomal dominant form that arises from mutations of the ELANE (formerly ELA2) gene on chromosome 19p13.3, which encodes neutrophil elastase. Over a hundred ELANE mutations have been found in SCN1. This same gene is mutated in cyclic neutropenia.
SCN2 is caused by heterozygous (autosomal dominant) mutation of the GFI1 gene on chromosome 1p22. GFI1 is a repressor of several transcriptional processes, including ELANE, as well as miR-21 and miR-196b micro-RNAs which influence myelopoiesis.
SCN3 is the "classical", autosomal recessive form of Kostmann disease which arises from homozygous mutations in the HAX1 gene on chromosome 1p22.1. About one third of SCN3 individuals also have neurological changes including seizures, learning disabilities, or developmental delay.
SCN4 is caused by autosomal recessive mutation of the G6PC3 gene on 17q21. SCN4 is associated with structural cardiac abnormalities, enlarged liver, intermittent thrombocytopenia and a prominent superficial venous pattern. A subset of SCN4 has severe primary pulmonary hypertension and respiratory failure.
SCN5 arises from autosomal recessive Thr224Asn mutation in the VPS45 gene on chromosome 1q21.2. Unlike classical Kostmann disease, SCN5 also has defective platelet aggregation (thrombasthenia) and myelofibrosis. This type is refractory to granulocyte colony-stimulating factor. There is an absence of lysosomes in fibroblasts and depletion of alpha granules in platelets. Accelerated apoptosis occurs in the neutrophils and bone marrow.
X-linked SCN (SCNX) is caused by mutation in the WASP gene on Xp11.SCN occasionally may arise from SBDS mutations.

Usage
Severe congenital neutropenia (SCN) is used as the overarching term for all diseases that affect myelopoiesis most prominently. Kostmann syndrome can restrictively refer to Kostmann disease specifically, or can be used synonymously with SCN as an umbrella term. These syndrome subtypes are phenotypically similar despite arising from different gene abnormalities.Kostmann disease is a form of severe congenital neutropenia (SCN), specifically type 3 (SCN3), which is a rare autosomal recessive condition in which severe  chronic  neutropenia is detected soon after birth. The disorder was discovered in 1956 in an extended family in northern Sweden by Rolf Kostmann, a Swedish doctor.Although mutations of more than 15 genes cause severe congenital neutropenia (in a general sense) not all of these are usually considered as SCN.  Clinical usage excludes two broad categories of congenital neutropenia. Diseases are excluded that overtly affect multiple systems rather than impacting myelopoiesis most prominently. Thus SCN excludes the severe neutropenia which can occur in congenital diseases such as Shwachman–Diamond syndrome, Barth syndrome, Chédiak–Higashi syndrome, WHIM syndrome, and glycogen storage disease type Ib. A further group of other miscellaneous inherited disorders, such as hyper IgM syndrome, Hermansky–Pudlak syndrome (HPS), Griscelli syndrome (GS), PN, P14 deficiency, Cohen syndrome, Charcot–Marie–Tooth disease (CMT) can show congenital neutropenia, but lack bone marrow findings typical of SCN.This group of diseases may also have additional features such as partial albinism, retinopathy, or neuropathy, and are not inclined to degenerate into acute myelogenous leukemia.

GATA2 deficiency
GATA2 deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. These autosomal dominant mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the genes product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to a more serious disorder. A small but significant percentage of individuals with GATA2 deficiencys present with congenital neutropenia. This neutropenia is typically mild, often persists for years, and therefore is not a Kostmann syndrome disorder. Over time, however, the deficiency commonly progresses to include thrombocytopenia, increases susceptibility to infections due to, e.g. atypical mycobacteria or human papillomavirus, dysfunction of non-hematological organs, the myelodysplastic syndrome, and/or a leukemia, particularly acute myelogenous leukemia.

Pathophysiology
The various mutations are responsible for the untimely initiation of apoptosis in myelocytes, usually at the promyelocyte stage, leading to their premature destruction or maturation arrest in the bone marrow. The ineffective production of neutrophils leads to a decrease in the absolute neutrophil count and a subsequent increased susceptibility to infections. There may be, in addition, other underlying molecular/genetic changes producing DNA mutations and genome instability, which contribute to initiation and progression of this disease.

Diagnosis
An absolute neutrophil count (ANC) chronically less than 500/mm3, usually less than 200/mm3, is the main sign of Kostmanns.  Other elements include the severity of neutropenia, the chronology (from birth; not emerging later), and other normal findings (hemoglobin, platelets, general body health). Isolated neutropenia in infants can occur in viral infections, autoimmune neutropenia of infancy, bone marrow suppression from a drug or toxin, hypersplenism, and passive placental transfer of maternal IgG.A bone marrow test can assist in diagnosis. The bone marrow usually shows early granulocyte precursors, but myelopoietic development stops ("arrests") at the promyelocyte and/or myelocyte stage, so that few maturing forms are seen. Neutrophil survival is normal.

Treatment
Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term.Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival.

See also
Neutropenia
Cyclic neutropenia
GATA2 deficiency

References
Klein, Christoph (2011). "Genetic Defects in Severe Congenital Neutropenia: Emerging Insights into Life and Death of Human Neutrophil Granulocytes" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Chemotherapy-induced acral erythema and can you explain it in depth? [/INST] Chemotherapy-induced acral erythema, also known as palmar-plantar erythrodysesthesia or hand-foot syndrome is reddening, swelling, numbness and desquamation (skin sloughing or peeling) on palms of the hands and soles of the feet (and, occasionally, on the knees, elbows, and elsewhere) that can occur after chemotherapy in patients with cancer. Hand-foot syndrome is also rarely seen in sickle-cell disease. These skin changes usually are well demarcated. Acral erythema typically disappears within a few weeks after discontinuation of the offending drug.

Signs and symptoms
The symptoms can occur anywhere between days to months after administration of the offending medication, depending on the dose and speed of administration. The patient first experiences tingling and/or numbness of the palms and soles. This is followed 2-4 days later by bright redness, which is symmetrical and sharply defined.In severe cases this may be followed by burning pain and swelling, blistering and ulceration, peeling of the skin. Healing occurs without scarring unless there has been skin ulceration or necrosis (skin loss/death). With each subsequent cycle of chemotherapy, the reaction will appear more quickly, be more severe and will take longer to heal.

Causes
Acral erythema is a common adverse reaction to cytotoxic chemotherapy drugs, particularly cabozantinib, cytarabine, doxorubicin, and fluorouracil and its prodrug capecitabine.Targeted cancer therapies, especially the tyrosine kinase inhibitors sorafenib and sunitinib, have also been associated with a high incidence of acral erythema. However, acral erythema due to tyrosine kinase inhibitors seems to differ somewhat from acral erythema due to classic chemotherapy drugs.

Pathogenesis
The cause of Palmar-plantar erythrodysesthesia (PPE) is unknown. Existing hypotheses are based on the fact that only the hands and feet are involved and posit the role of temperature differences, vascular anatomy, differences in the types of cells (rapidly dividing epidermal cells and eccrine glands).In the case of PPE caused by PLD, the following mechanism has been demonstrated: sweat deposits and spreads the drug on the skin surface; then the drug penetrates into the stratum corneum like an external agent; palms and soles have high density of sweat glands, and their stratum corneum is approximately 10 times thicker than the rest of the body, and becomes an efficient long-term reservoir for the penetrating PLD, which was deposited on the skin before.

Diagnosis
Painful red swelling of the hands and feet in a patient receiving chemotherapy is usually enough to make the diagnosis. The problem can also arise in patients after bone marrow transplants, as the clinical and histologic features of PPE can be similar to cutaneous manifestations of acute (first three weeks) graft-versus-host disease. It is important to differentiate PPE, which is benign, from the more dangerous graft-versus-host disease. As time progresses, patients with graft-versus-host disease progress to have other body parts affected, while PPE is limited to hands and feet. Serial biopsies every 3 to 5 days can also be helpful in differentiating the two disorders.

Prevention
The cooling of hands and feet during chemotherapy may help prevent PPE. Support for this and a variety of other approaches to treat or prevent acral erythema comes from small clinical studies, although none has been proven in a randomised controlled clinical trial of sufficient size.Modifying some daily activities to reduce friction and heat exposure to your hands and feet for a period of time following treatment (approximately one week after IV medication, much as possible during the time you are taking oral (by mouth) medication such as capecitabine).
Avoid long exposure of hands and feet to hot water such as washing dishes, long showers, or tub baths.
Short showers in tepid water will reduce exposure of the soles of your feet to the drug.
Dishwashing gloves should not be worn, as the rubber will hold heat against your palms.
Avoid increased pressure on the soles of the feet or palms of hands.
No jogging, aerobics, power walking, jumping - avoid long days of walking.
You should also avoid using garden tools, household tools such as screwdrivers, and other tasks where you are squeezing your hand on a hard surface.
Using knives to chop food may also cause excessive pressure and friction on your palms.

Treatment
The main treatment for acral erythema is discontinuation of the offending drug, and symptomatic treatment to provide analgesia, lessen edema, and prevent superinfection. However, the treatment for the underlying cancer of the patient must not be neglected. Often, the discontinued drug can be substituted with another cancer drug or cancer treatment.Symptomatic treatment can include wound care, elevation, and pain medication. Various emollients (creams) are recommended to keep skin moist.   Corticosteroids and pyridoxine have also been used to relieve symptoms. Other studies do not support the conclusion. A number of additional remedies are listed in recent medical literature. Among them henna and 10% uridine ointment which went through clinical trial.

Prognosis
Hand-foot invariably recurs with the resumption of chemotherapy. Long-term chemotherapy may also result in reversible palmoplantar keratoderma. Symptoms resolve 1–2 weeks after cessation of chemotherapy (Apisarnthanarax and Duvic 2003) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Long face syndrome and can you explain it in depth? [/INST] Long face syndrome, also referred to as skeletal open bite, is a relatively common condition characterised by excessive vertical facial development </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Id reaction and can you explain it in depth? [/INST] Id reactions (also known as "disseminated eczema," and "generalized eczema") are types of acute dermatitis developing after days or weeks at skin locations distant from the initial inflammatory or infectious site. They can be localised or generalised. This is also known as an autoeczematous response and there must be an identifiable initial inflammatory or infectious skin problem which leads to the generalised eczema. Often intensely itchy, the red papules and pustules can also be associated with blisters and scales and are always remote from the primary lesion. It is most commonly a blistering rash with itchy vesicles on the sides of fingers and feet as a reaction to fungal infection on the feet, athletes foot. Stasis dermatitis, allergic contact dermatitis, acute irritant contact eczema and infective dermatitis have been documented as possible triggers, but the exact cause and mechanism is not fully understood. Several other types of id reactions exist including erythema nodosum, erythema multiforme, Sweets syndrome and urticaria.

Presentation
Complications
Id reactions left untreated may become infected with bacteria.

Causes
Causes include infection with dermatophytosis, Mycobacterium, viruses, bacteria and parasites. Eczematous conditions including contact allergic dermatitis and stasis dermatitis as well as stitches and trauma have also been associated with id reactions. Radiation treatment of tinea capitis has been reported as triggering an id reaction.

Pathogenesis
Potential explanations include

Atypical immune recognition of autologous skin antigens
Stimulation of normal T cells by changing skin constituents
Lower threshold for skin irritation
Spreading of infectious antigens causing a secondary response
Hematogenous dissemination of cytokines from the primary site of inflammation

Diagnosis
Although there are a multitude of varying appearances, the id reaction often presents with symmetrical red patches of eczema with papules and vesicles, particularly on the outer sides of the arms, face and trunk which occur suddenly and are intensely itchy occur a few days to a week after the initial allergic or irritant dermatitis. Most commonly, athletes foot can lead to localised vesicles on hands, bacterial infections to erythema nodosum and herpes simplex virus to erythema multiforme.The diagnosis is frequently made by treating the initial triggering skin problem and observing the improvement in the eczematous rash. Both the initial skin problem and the id reaction must be observed to make the diagnosis.Not all dyshidrotic rashes are
id reactions, but id reactions are often dyshidrotic-like.Initial tests may include isolating a fungus by taking a swab and sending it for culture </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Fungal sinusitis and can you explain it in depth? [/INST] Fungal sinusitis is the inflammation of the lining mucosa of the paranasal sinuses due to fungal infection. It occurs in people with reduced immunity. The maxillary sinus is the most commonly involved. Fungi responsible for fungal sinusitis are Aspergillus fumigatus (90%), Aspergillus flavus, and Aspergillus niger. Fungal sinusitis occurs most commonly in middle-aged populations. Diabetes mellitus is the most common risk factor involved.

Types
The types of fungal sinusitis are based on invasive and non-invasive as follows:
InvasiveAcute fulminant
Chronic invasive
GranulomatousNon InvasiveSaprophytic infection
Sinus fungal ball
Eosinophil related FRS including AFRSFulminant

Difference between non-invasive, invasive and fulminant fungal sinusitis
The type of fungal disease highly depends on the immunity of the patient. When a person has low immunity, they can get non-invasive fungal sinusitis, where the fungus will infect only the skin lining of the nasal and sinus cavity. When the immunity gets lowered, it will turn into invasive fungal sinusitis, and the infection can seep into the tissues making the infection dangerous. A person can have both non-invasive and invasive fungal sinusitis at the same time at different locations.Fulminant is the rarest and the most dangerous infection that can occur when immunity is too low. In this type of disease, the infection will not only seep into the tissues but also into blood vessels. Although it comes under invasive technically, when we say invasive fungal sinusitis we often refer to non-fulminant invasive fungal sinusitis as we can clearly distinguish both irrespective of the fact that symptoms are the same. The differentiating factor between invasive and fulminant infections is that the progress of the disease is very rapid in fulminant. The progress of the disease is so quick that it can kill a person in a month if not treated. One of the most common type of fulminant fungal infection is mucormycosis.

Signs and symptoms
Individuals with the condition of fungal sinusitis mostly present with features that include facial pain and pain around the eyes, nasal congestion, rhinorrhea(running nose), headache, later there may be ophthalmoplegia (paralysis of ocular muscles).

Pathophysiology
The mechanism of fungal sinusitis depends on which form, such as:

Acute fulminant form – the fungus invades into vessels causing thrombosis, necrosis with minimum inflammation
Chronic invasive – fungal hyphae invades tissue leaving necrosis with minimal inflammation
Granulomatous form – invasive hyphae invades tissue with inflammation and non-caseating granuloma (with foreign bodies).
Saprophytic infection – growth of fungus seen on mucous crusts within sinus cavity.
Sinus fungal ball – sequestration of fungal hyphae as densely tangled, and has gritty matted appearance.
Eosinophil related Allergic fungal sinusitis – though not completely understood, a possible mechanism sees the protein component of fungus elicits IgE mediated allergic mucosal inflammation.

Diagnosis
In terms of diagnosis, the clinical examination gives an idea about fungal sinusitis, as well as:

Suggestive clinical features include - multiple recurrent episodes, persistent pathology, and absent ability to smell (the Eustachian tube may also be affected).
X-Ray - can be done if the diagnosis is not certain.
CT – can document the presence of sinusitis, in the coronal views
MRI – used to find the CNS spread (extent of the disease), to evaluate individuals who demonstrate signs of invasive fungal sinusitis
Histology studies

Treatment
Treatment for fungal sinusitis can include surgical debridement; helps by slowing progression of disease thus allowing time for recovery additionally we see the options below:

In cases where the fungus has invaded the sinus tissue, echinocandins, oral voriconazole, and I.V amphotericin may be used
For allergic fungal sinusitis, systemic corticosteroids like prednisolone, methylprednisolone are added for their anti-inflammatory effect, bronchodilators and expectorants help to clear secretions in the sinuses.

Epidemiology
Though it is widely held that fungal infections of the nose and paranasal sinuses are not common, most agree that their frequency has been increasing over past decades.

See also
Granuloma

References
Further reading
Thaler, Erica; Kennedy, David W </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Calf (leg) and can you explain it in depth? [/INST] The calf (PL: calves; Latin: sura) is the back portion of the lower leg in human anatomy. The muscles within the calf correspond to the posterior compartment of the leg. The two largest muscles within this compartment are known together as the calf muscle and attach to the heel via the Achilles tendon. Several other, smaller muscles attach to the knee, the ankle, and via long tendons to the toes.

Etymology
From Middle English calf, kalf, from Old Norse kalfi, possibly derived from the same Germanic root as English calf ("young cow"). Cognate with Icelandic kálfi ("calf of the leg"). Calf and calf of the leg are documented in use in Middle English circa AD 1350 and AD 1425 respectively.Historically, the absence of calf, meaning a lower leg without a prominent calf muscle, was regarded by some authors as a sign of inferiority: it is well known that monkeys have no calves, and still less do they exist among the lower orders of mammals.

Structure
The calf is composed of the muscles of the posterior compartment of the leg: The gastrocnemius and soleus (composing the triceps surae muscle) and the tibialis posterior. The sural nerve provides innervation.

Clinical significance
Medical conditions that result in calf swelling among other symptoms include deep vein thrombosis compartment syndrome, Achilles tendon rupture, and varicose veins.
Idiopathic leg cramps are common and typically affect the calf muscles at night. Edema also is common and in many cases idiopathic. In a small study of factory workers in good health, wearing compression garments helped to reduce edema and the pain associated with edema </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Neurosarcoidosis and can you explain it in depth? [/INST] Neurosarcoidosis (sometimes shortened to neurosarcoid) refers to a type of sarcoidosis, a condition of unknown cause featuring granulomas in various tissues, in this type involving the central nervous system (brain and spinal cord). Neurosarcoidosis can have many manifestations, but abnormalities of the cranial nerves (a group of twelve nerves supplying the head and neck area) are the most common. It may develop acutely, subacutely, and chronically. Approximately 5–10 percent of people with sarcoidosis of other organs (e.g. lung) develop central nervous system involvement. Only 1 percent of people with sarcoidosis will have neurosarcoidosis alone without involvement of any other organs. Diagnosis can be difficult, with no test apart from biopsy achieving a high accuracy rate. Treatment is with immunosuppression. The first case of sarcoidosis involving the nervous system was reported in 1905.

Signs and symptoms
Neurological
Abnormalities of the cranial nerves are present in 50–70 percent of cases. The most common abnormality is involvement of the facial nerve, which may lead to reduced power on one or both sides of the face (65 percent resp 35 percent of all cranial nerve cases), followed by reduction in visual perception due to optic nerve involvement. Rarer symptoms are double vision (oculomotor nerve, trochlear nerve or abducens nerve), decreased sensation of the face (trigeminal nerve), hearing loss or vertigo (vestibulocochlear nerve), swallowing problems (glossopharyngeal nerve) and weakness of the shoulder muscles (accessory nerve) or the tongue (hypoglossal nerve). Visual problems may also be the result of papilledema (swelling of the optic disc) due to obstruction by granulomas of the normal cerebrospinal fluid (CSF) circulation.Seizures (mostly of the tonic-clonic/"grand mal" type) are present in about 15 percent and may be the presenting phenomenon in 10 percent.Meningitis (inflammation of the lining of the brain) occurs in 3–26 percent of cases. Symptoms may include headache and nuchal rigidity (being unable to bend the head forward). It may be acute or chronic.Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the internal capsule would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause headache and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised intracranial pressure and hydrocephalus.Involvement of the spinal cord is rare, but can lead to abnormal sensation or weakness in one or more limbs, or cauda equina symptoms (incontinence to urine or stool, decreased sensation in the buttocks).

Endocrine
Granulomas in the pituitary gland, which produces numerous hormones, is rare but leads to any of the symptoms of hypopituitarism: amenorrhoea (cessation of the menstrual cycle), diabetes insipidus (dehydration due to inability to concentrate the urine), hypothyroidism (decreased activity of the thyroid) or hypocortisolism (deficiency of cortisol).

Mental and other
Psychiatric problems occur in 20 percent of cases; many different disorders have been reported, e.g. depression and psychosis. Peripheral neuropathy has been reported in up to 15 percent of cases of neurosarcoidosis.Other symptoms due to sarcoidosis of other organs may be uveitis (inflammation of the uveal layer in the eye), dyspnoea (shortness of breath), arthralgia (joint pains), lupus pernio (a red skin rash, usually of the face), erythema nodosum (red skin lumps, usually on the shins), and symptoms of liver involvement (jaundice) or heart involvement (heart failure).

Pathophysiology
Sarcoidosis is a disease of unknown cause that leads to the development of granulomas in various organs. While the lungs are typically involved, other organs may equally be affected. Some subforms of sarcoidosis, such as Löfgren syndrome, may have a particular precipitant and have a specific course. It is unknown which characteristics predispose sarcoidosis patients to brain or spinal cord involvement.

Diagnosis
The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by biopsy (surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, lumbar puncture, electroencephalography (EEG) and evoked potential (EP) studies. If the diagnosis of sarcoidosis is suspected, typical X-ray or CT appearances of the chest may make the diagnosis more likely; elevations in angiotensin-converting enzyme and calcium in the blood, too, make sarcoidosis more likely. In the past, the Kveim test was used to diagnose sarcoidosis. This now obsolete test had a high (85 percent) sensitivity, but required spleen tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate granulomas (collections of inflammatory cells) rich in epithelioid cells and surrounded by other immune system cells (e.g. plasma cells, mast cells). Biopsy may be performed to distinguish mass lesions from tumours (e.g. gliomas).MRI with gadolinium enhancement is the most useful neuroimaging test. This may show enhancement of the pia mater or white matter lesions that may resemble the lesions seen in multiple sclerosis.Lumbar puncture may demonstrate raised protein level, pleiocytosis (i.e. increased presence of both lymphocytes and neutrophil granulocytes) and oligoclonal bands. Various other tests (e.g. ACE level in CSF) have little added value.

Criteria
Some recent papers propose to classify neurosarcoidosis by likelihood:
Definite neurosarcoidosis can only be diagnosed by plausible symptoms, a positive biopsy and no other possible causes for the symptoms
Probable neurosarcoidosis can be diagnosed if the symptoms are suggestive, there is evidence of central nervous system inflammation (e.g. CSF and MRI), and other diagnoses have been excluded. A diagnosis of systemic sarcoidosis is not essential.
Possible neurosarcoidosis may be diagnosed if there are symptoms not due to other conditions but other criteria are not fulfilled.

Treatment
Neurosarcoidosis, once confirmed, is generally treated with glucocorticoids such as prednisolone. If this is effective, the dose may gradually be reduced (although many patients need to remain on steroids long-term, frequently leading to side-effects such as diabetes or osteoporosis). Methotrexate, hydroxychloroquine, cyclophosphamide, pentoxifylline, thalidomide and infliximab have been reported to be effective in small studies. In patients unresponsive to medical treatment, radiotherapy may be required. If the granulomatous tissue causes obstruction or mass effect, neurosurgical intervention is sometimes necessary. Seizures can be prevented with anticonvulsants, and psychiatric phenomena may be treated with medication usually employed in these situations.

Prognosis
Of the phenomena occurring in neurosarcoid, only facial nerve involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena. The mortality rate is estimated at 10 percent

Epidemiology
Sarcoidosis has a prevalence of 40 per 100,000 in the general population.  However, though those with the GG genotype at rs1049550 in the ANXA11 gene were found to have 1.5–2.5 times higher odds of sarcoidosis compared to those with the AG genotype, while those with the AA genotype had about 1.6 times lower odds.  Furthermore, those with Common Variable Immunodeficiency (CVID) may be at even higher risk. One study of 80 CVID patients found eight of these had sarcoidosis, suggesting as high a prevalence in CVID populations as one in 10 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Periventricular leukomalacia and can you explain it in depth? [/INST] Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis (more often coagulation) of white matter near the lateral ventricles. It can affect newborns and  (less commonly) fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. The white matter in preterm born children is particularly vulnerable during the third trimester of pregnancy when white matter developing takes place and the myelination process starts around 30 weeks of gestational age.This pathology of the brain was described under various names ("encephalodystrophy", "ischemic necrosis", "periventricular infarction", "coagulation necrosis", "leukomalacia," "softening of the brain", "infarct periventricular white matter", "necrosis of white matter", "diffuse symmetrical periventricular leukoencephalopathy"), and more often by German scientists, but the worldwide dissemination was the term periventricular leukomalacia, introduced in 1962 B. A. Banker and J. C. Larroche. The term can be misleading, as there is no softening of the tissue in PVL. V. V. Vlasyuk and V. P. Tumanov in 1985 published the worlds first monograph devoted to PVL. Vlasyuk (1981) first revealed the high incidence of optic radiation lesions and demonstrated that PVL - a persistent process that the old necrosis can join a new, foci of PVL may be at different stages of development.
In the process of morphogenesis focuses PVL pass through three stages: 1) necrosis, 2) resorption, and 3) the formation gliosis scars or cysts. Cysts occur when large and confluent focuses of PVL, with mixed necrosis (kollikvacia in the center and coagulation rim at the periphery). Around the foci is generally defined area of other lesions of the brain white matter - the death of prooligodendrocytes, proliferation mikrogliocytes and astrocytes, swelling, bleeding, loss of capillaries, and others (the so-called "diffuse component PVL"). However, diffuse lesions without necrosis are not PVL.

Presentation
It is often impossible to identify PVL based on the patients physical or behavioral characteristics. The white matter in the periventricular regions is involved heavily in motor control, and so individuals with PVL often exhibit motor problems. However, since healthy newborns (especially premature infants) can perform very few specific motor tasks, early deficits are very difficult to identify. As the individual develops, the areas and extent of problems caused by PVL can begin to be identified; however, these problems are usually found after an initial diagnosis has been made.
The extent of signs is strongly dependent on the extent of white matter damage: minor damage leads to only minor deficits or delays, while significant white matter damage can cause severe problems with motor coordination or organ function. Some of the most frequent signs include delayed motor development, vision deficits, apneas, low heart rates, and seizures.

Delayed motor development
Delayed motor development of infants affected by PVL has been demonstrated in multiple studies. One of the earliest markers of developmental delays can be seen in the leg movements of affected infants, as early as one month of age. Those with white matter injury often exhibit "tight coupling" of leg joints (all extending or all flexing) much longer than other infants (premature and full-term). Additionally, infants with PVL may not be able to assume the same positions for sleeping, playing, and feeding as premature or full-term children of the same age. These developmental delays can continue throughout infancy, childhood, and adulthood.

Vision deficits
Premature infants often exhibit visual impairment and motor deficits in eye control immediately after birth. However, the correction of these deficits occurs "in a predictable pattern" in healthy premature infants, and infants have vision comparable to full-term infants by 36 to 40 weeks after conception. Infants with PVL often exhibit decreased abilities to maintain a steady gaze on a fixed object and create coordinated eye movements. Additionally, children with PVL often exhibit nystagmus, strabismus, and refractive error.

Seizures
Occurrence of seizures is often reported in children with PVL. In an Israel-based study of infants born between 1995 and 2002, seizures occurred in 102 of 541, or 18.7%, of PVL patients. Seizures are typically seen in more severe cases of PVL, affecting patients with greater amounts of lesions and those born at lower gestational ages and birth weights.

Causes
Predisposing factors
Those generally considered to be at greatest risk for PVL are premature, very low birth-weight infants. It is estimated that approximately 3-4% of infants who weigh less than 1,500 g (3.3 lb) have PVL, and 4-10% of those born prior to 33 weeks of gestation (but who survive more than three days postpartum) have the disorder.  Gestational CMV infection also produces PVL in neonates.

Injury pathway
Two major factors appear to be involved in the development of PVL:  (1) decreased blood or oxygen flow to the periventricular region (the white matter near the cerebral ventricles) and (2) damage to glial cells, the cells that support neurons throughout the nervous system. These factors are especially likely to interact in premature infants, resulting in a sequence of events that leads to the development of white matter lesions.
The initial hypoxia (decreased oxygen flow) or ischemia (decreased blood flow) can occur for a number of reasons. Fetal blood vessels are thin-walled structures, and it is likely that the vessels providing nutrients to the periventricular region cannot maintain a sufficient blood flow during episodes of decreased oxygenation during development. Additionally, hypotension resulting from fetal distress or cesarean section births can lead to decreased blood and oxygen flow to the developing brain. These hypoxic-ischemic incidents can cause damage to the blood brain barrier (BBB), a system of endothelial cells and glial cells that regulates the flow of nutrients to the brain. A damaged BBB can contribute to even greater levels of hypoxia. Alternatively, damage to the BBB can occur due to maternal infection during fetal development, fetal infections, or infection of the newly delivered infant. Because their cardiovascular and immune systems are not fully developed, premature infants are especially at risk for these initial insults.
Damage caused to the BBB by hypoxic-ischemic injury or infection sets off a sequence of responses called the inflammatory response. Immediately after an injury, the nervous system generates "pro-inflammatory" cytokines, which are molecules used to coordinate a response to the insult. These cytokines are toxic to the developing brain, and their activity in an effort to respond to specific areas of damaged tissue is believed to cause "bystander damage" to nearby areas that were not affected by the original insult. Further damage is believed to be caused by free radicals, compounds produced during ischemic episodes. The processes affecting neurons also cause damage to glial cells, leaving nearby neurons with little or no support system.
It is thought that other factors might lead to PVL, and researchers are studying other potential pathways. A 2007 article by Miller, et al., provides evidence that white-matter injury is not a condition limited to premature infants: full-term infants with congenital heart diseases also exhibit a "strikingly high incidence of white-matter injury."  In a study described by Miller, of 41 full-term newborns with congenital heart disease, 13 infants (32%) exhibited white matter injury.

Diagnosis
As previously noted, there are often few signs of white matter injury in newborns. Occasionally, physicians can make the initial observations of extreme stiffness or poor ability to suckle. The preliminary diagnosis of PVL is often made using imaging technologies. In most hospitals, premature infants are examined with ultrasound soon after birth to check for brain damage. Severe white matter injury can be seen with a head ultrasound; however, the low sensitivity of this technology allows for some white matter damage to be missed. Magnetic resonance imaging (MRI) is much more effective at identifying PVL, but it is unusual for preterm infants to receive an MRI unless they have had a particularly difficult course of development (including repeated or severe infection, or known hypoxic events during or immediately after birth). No agencies or regulatory bodies have established protocols or guidelines for screening of at-risk populations, so each hospital or doctor generally makes decisions regarding which patients should be screened with a more sensitive MRI instead of the basic head ultrasound.
PVL is overdiagnosed by neuroimaging studies and the other white matter lesions of the brain are underestimated. It is important to differentiate PVL from the following major white matter lesions in the cerebral hemispheres: edematous hemorrhagic leukoencephalopathy (OGL), telentsefalny gliosis (TG), diffuse leukomalacia (DFL), subcortical leukomalacia (SL), periventricular hemorrhagic infarction (PHI), intracerebral hemorrhage ( ICH), multicystic encephalomalacia (ME), subendymal pseudocyst. Diffuse white matter lesions of the cerebral hemispheres of the brain, accompanied by softening and spreading to the central and subcortical areas are more likely DFL, PHI and ME.

Prevention
Preventing or delaying premature birth is considered the most important step in decreasing the risk of PVL. Common methods for preventing a premature birth include self-care techniques (dietary and lifestyle decisions), bed rest, and prescribed anti-contraction medications. Avoiding premature birth allows the fetus to develop further, strengthening the systems affected during the development of PVL.
An emphasis on prenatal health and regular medical examinations of the mother can also notably decrease the risk of PVL. Prompt diagnosis and treatment of maternal infection during gestation reduces the likelihood of large inflammatory responses. Additionally, treatment of infection with steroids (especially in the 24–34 weeks of gestation) have been indicated in decreasing the risk of PVL.It has also been suggested that avoiding maternal cocaine usage and any maternal-fetal blood flow alterations can decrease the risk of PVL. Episodes of hypotension or decreased blood flow to the infant can cause white matter damage.

Treatment
Current treatments
Currently, there are no treatments prescribed for PVL. All treatments administered are in response to secondary pathologies that develop as a consequence of the PVL. Because white matter injury in the periventricular region can result in a variety of deficits, neurologists must closely monitor infants diagnosed with PVL in order to determine the severity and extent of their conditions.
Patients are typically treated with an individualized treatment. It is crucial for doctors to observe and maintain organ function: visceral organ failure can potentially occur in untreated patients. Additionally, motor deficits and increased muscle tone are often treated with individualized physical and occupational therapy treatments.

Treatment challenges
The fetal and neonatal brain is a rapidly changing, developing structure. Because neural structures are still developing and connections are still being formed at birth, many medications that are successful for treatment and protection in the adult central nervous system (CNS) are ineffective in infants. Moreover, some adult treatments have actually been shown to be toxic to developing brains.

Future treatments
Although no treatments have been approved for use in human PVL patients, a significant amount of research is occurring in developing treatments for protection of the nervous system. Researchers have begun to examine the potential of synthetic neuroprotection to minimize the amount of lesioning in patients exposed to ischemic conditions.

Prognosis
The prognosis of patients with PVL is dependent on the severity and extent of white matter damage. Some children exhibit relatively minor deficits, while others have significant deficits and disabilities.

Minor tissue damage
Minor white matter damage usually is exhibited through slight developmental delays and deficits in posture, vision systems, and motor skills. Many patients exhibit spastic diplegia, a condition characterized by increased muscle tone and spasticity in the lower body. The gait of PVL patients with spastic diplegia exhibits an unusual pattern of flexing during walking.

Progression
Those patients with severe white matter injury typically exhibit more extensive signs of brain damage. Infants with severe PVL suffer from extremely high levels of muscle tone and frequent seizures. Children and adults may be quadriplegic, exhibiting a loss of function or paralysis of all four limbs.

Cerebral palsy
Many infants with PVL eventually develop cerebral palsy. The percentage of individuals with PVL who develop cerebral palsy is generally reported with significant variability from study to study, with estimates ranging from 20% to more than 60%. One of the reasons for this discrepancy is the large variability in severity of cerebral palsy. This range corresponds to the severity of PVL, which can also be quite variable. More white matter damage leads to more severe cerebral palsy; different subtypes are identified and diagnosed by a neurologist.
Despite the varying grades of PVL and cerebral palsy, affected infants typically begin to exhibit signs of cerebral palsy in a predictable manner. Typically, some abnormal neurological signs (such as those previously mentioned) are visible by the third trimester of pregnancy (28 to 40 weeks after conception), and definitive signs of cerebral palsy are visible by six to nine months of age.

Epilepsy
Another common but severe outcome of PVL patients is the development of epilepsy. The link between the two is not entirely clear; however, it appears that both genetic and early environmental factors are involved </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Berylliosis and can you explain it in depth? [/INST] Berylliosis, or chronic beryllium disease (CBD), is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds, a form of beryllium poisoning. It is distinct from acute beryllium poisoning, which became rare following occupational exposure limits established around 1950. Berylliosis is an occupational lung disease.
While there is no cure, symptoms can be treated.

Signs and symptoms
With single or prolonged exposure by inhalation the lungs may become sensitized to beryllium. Berylliosis has a slow onset and progression. Some people who are sensitized to beryllium may not have symptoms. Continued exposure causes the development of small inflammatory nodules, called granulomas. Of note, the authors of a 2006 study suggested that beryllium inhalation was not the only form of exposure and perhaps skin exposure was also a cause, as they found that a reduction in beryllium inhalation did not result in a reduction in CBD or beryllium sensitization.Granulomas are seen in other chronic diseases, such as tuberculosis and sarcoidosis, and it can occasionally be hard to distinguish berylliosis from these disorders. However, granulomas of CBD will typically be non-caseating, i.e. not characterized by necrosis and therefore not exhibiting a cheese-like appearance grossly.Ultimately, this process leads to restrictive lung disease (a decrease in diffusion capacity).
The earliest symptoms are typically cough and shortness of breath. Other symptoms include chest pain, joint aches, weight loss, and fever.
Rarely, one can get granulomas in other organs including the liver.
The onset of symptoms can range from weeks up to tens of years from the initial exposure. In some individuals, a single exposure to beryllium can cause berylliosis.

Pathogenesis
In susceptible persons, beryllium exposure can lead to a cell-mediated immune response. The T-cells become sensitized to beryllium. Each subsequent exposure leads to an immune response involving CD4+ helper T-lymphocytes and macrophages accumulating in the lungs. As this response continues macrophages, CD+4 T-lymphocytes and plasma cells aggregate together to form the noncaseating granulomas. When beryllium is phagocytized by macrophages, the beryllium triggers macrophage apoptosis, thereby reducing beryllium clearance from the lungs and eventually resulting in secondary necrosis and lysis. Eventually, the outcome is fibrosis of the lung.Several studies have shown that there is a genetic component to beryllium sensitivity. Specifically, those beryllium exposed workers with a mutation at the HLA-DPB1 Glu69 position have increased prevalence of beryllium sensitization and CBD.  The HLA-DPB1 gene is important for MHC class II molecule function on antigen presenting cells.According to the International Agency for Research on Cancer (IARC), beryllium and beryllium compounds are Category 1 carcinogens; they are carcinogenic to both animals and humans.

Diagnosis
The differential diagnosis for berylliosis includes:
Sarcoidosis
Granulomatous lung diseases
Tuberculosis
Fungal infections (e.g., histoplasmosis)
Granulomatosis with polyangiitis
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
AsthmaOf these possibilities, berylliosis presents most similarly to sarcoidosis. Some studies suggest that up to 6% of all cases of sarcoidosis are actually berylliosis.Definitive diagnosis of berylliosis is based on history of beryllium exposures, documented beryllium sensitivity and granulomatous inflammation on lung biopsy. Given the invasive nature of a lung biopsy, diagnosis can also be based on clinical history consistent with berylliosis, abnormal chest x-ray or CT scan findings, and abnormalities in pulmonary function tests.Establishing beryllium sensitivity is the first step in diagnosis. The beryllium lymphocyte proliferation test (BeLPT) is the standard way of determining sensitivity to beryllium. The test is performed by acquiring either peripheral blood or fluid from a bronchial alveolar lavage, and lymphocytes are cultured with beryllium sulfate. Cells are then counted and those with elevated number of cells are considered abnormal. Those exposed persons with two abnormal BeLPT tested with peripheral blood, or one abnormal and one borderline result, are considered beryllium sensitized. Also, those with one abnormal BeLPT tested with fluid from a bronchial alveolar lavage are considered sensitized.Chest radiography findings of berylliosis are non-specific. Early in the disease radiography findings are usually normal. In later stages interstitial fibrosis,  pleural irregularities, hilar lymphadenopathy and ground-glass opacities have been reported. Findings on CT are also not specific to berylliosis. Findings that are common in CT scans of people with berylliosis include parenchymal nodules in early stages. One study found that ground-glass opacities were more commonly seen on CT scan in berylliosis than in sarcoidosis. In later stages hilar lymphadenopathy, interstitial pulmonary fibrosis and pleural thickening.

Classification
Berylliosis is an occupational disease. Relevant occupations are those where beryllium is mined, processed or converted into metal alloys, or where machining of metals containing beryllium and recycling of scrap alloys occurs. It is associated with aerospace manufacturing, microwave semiconductor electronics, beryllium mining or manufacturing of fluorescent light bulbs (which once contained beryllium compounds in their internal phosphor coating). Beryllia was used in lamp manufacture because of ceramics obvious virtues for insulation and heat resistance, and also because beryllia could be made transparent. Certain welding anodes along with other electrical contacts and even non-sparking tools are made of beryllium copper alloy and the subsequent machining of such materials would cause the disease as well.

Prevention
Typical levels of beryllium that industries may release into the air are of the order of 0.01 µg/m3, averaged over a 30-day period, or 2 µg/m3 of workroom air for an 8-hour work shift. Compliance with the current U.S. Occupational Safety and Health Administration (OSHA) permissible exposure limit for beryllium of 2 µg/m3 has been determined to be inadequate to protect workers from developing beryllium sensitization and CBD. The American Conference of Governmental Industrial Hygienists (ACGIH), which is an independent organization of experts in the field of occupational health, has proposed a threshold limit value (TLV) of 0.05 µg/m3 in a 2006 Notice of Intended Change (NIC). This TLV is 40 times lower than the current OSHA permissible exposure limit, reflecting the ACGIH analysis of best available peer-reviewed research data concerning how little airborne beryllium is required to cause sensitization and CBD.Because it can be difficult to control industrial exposures to beryllium, it is advisable to use any methods possible to reduce airborne and surface contamination by beryllium, to minimize the use of beryllium and beryllium-containing alloys whenever possible, and to educate people about the potential hazards if they are likely to encounter beryllium dust or fumes. It is important to damp wipe metallographic preparation equipment to prevent accumulation of dry particles. Sectioning, grinding, and polishing must be performed under sufficiently vented hoods equipped with special filters.On 29 January 2009, the Los Alamos National Laboratory announced it was notifying nearly 2,000 current and former employees and visitors that they may have been exposed to beryllium in the lab and may be at risk of disease. Concern over possible exposure to the material was first raised in November 2008, when a box containing beryllium was received at the laboratorys short-term storage facility.

Treatment
There is no cure for berylliosis; the goals of treatment are to reduce symptoms and slow the progression of disease.Although the evidence that stopping exposure to beryllium decreases progression of the disease is limited, it is still considered to be an accepted approach to treatment in any stage of disease.People with early stages of disease, without lung function abnormalities or clinical symptoms, are periodically monitored with physical exams, pulmonary function testing and radiography.Once clinical symptoms or significant abnormalities in pulmonary function testing appear, treatments include oxygen and oral corticosteroids and whatever supportive therapy is required.

Outcomes
Overall mortality rates are 5–38%.

Epidemiology
The number of workers in the United States exposed to beryllium vary but has been estimated to be as high as 800,000 during the 1960s and 1970s. A more recent study from 2004 estimated the number of exposed workers in the United States to be around 134,000.The rate of workers becoming sensitized to beryllium varies based on genetics and exposure levels. In one study researchers found the prevalence of beryllium sensitization to range from 9 - 19% depending on the industry. Many workers who are found to be sensitive to beryllium also meet the diagnostic criteria for CBD. In one study of nuclear workers, among those who were sensitized to beryllium, 66% were found to have CBD as well. The rate of progression from beryllium sensitization to CBD has been estimated to be approximately 6-8% per year. Stopping exposure to beryllium in those sensitized has not been definitively shown to stop the progression to CBD.The overall prevalence of CBD among workers exposed to beryllium has ranged from 1 – 5% depending on industry and time period of study.The general population is unlikely to develop acute or chronic beryllium disease because ambient air levels of beryllium are normally very low (<0.03 ng/m3).  However, a study found 1% of people living within 3/4 of a mile of a beryllium plant in Lorain, Ohio, had berylliosis after exposure to concentrations estimated to be less than 1 milligram per cubic metre of air. In the United States the Beryllium Case Registry contained 900 records, early cases relating to extraction and fluorescent lamp manufacture, later ones coming from the aerospace, ceramics and metallurgical industries.

History
Since the 1920s, beryllium has been used in electronics, ceramics, research and development labs, aircraft, and the atomic energy and defense industry. Cases of bronchitis and pneumonia-like symptoms were reported in Germany and Russia in the 1930s among workers mining and refining beryllium. By 1946, a cluster of cases associated with fluorescent lamp manufacturers were apparent in the United States, and the lamp industry stopped using beryllium in 1949. At that time, most construction trades and industries were unaware of the potential risks associated with beryllium exposure.It occasionally killed early workers in nuclear weapons design, such as Herbert L </s>