Persius/hicric huggingface dataset:
Amphotericin B liposomal description

# Description
AmBisome for Injection is a sterile, non-pyrogenic lyophilized product for intravenous infusion. Each vial contains 50 mg of amphotericin B, USP, intercalated into a liposomal membrane consisting of approximately 213 mg hydrogenated soy phosphatidylcholine; 52 mg cholesterol, NF; 84 mg distearoylphosphatidylglycerol; 0.64 mg alpha tocopherol, USP; together with 900 mg sucrose, NF; and 27 mg disodium succinate hexahydrate as buffer. Following reconstitution with Sterile Water for Injection, USP, the resulting pH of the suspension is between 5-6.
AmBisome is a true single bilayer liposomal drug delivery system. Liposomes are closed, spherical vesicles created by mixing specific proportions of amphophilic substances such as phospholipids and cholesterol so that they arrange themselves into multiple concentric bilayer membranes when hydrated in aqueous solutions. Single bilayer liposomes are then formed by microemulsification of multilamellar vesicles using a homogenizer. AmBisome consists of these unilamellar bilayer liposomes with amphotericin B intercalated within the membrane. Due to the nature and quantity of amphophilic substances used, and the lipophilic moiety in the amphotericin B molecule, the drug is an integral part of the overall structure of the AmBisome liposomes. AmBisome contains true liposomes that are less than 100 nm in diameter. A schematic depiction of the liposome is presented below.
Note: Liposomal encapsulation or incorporation into a lipid complex can substantially affect a drugs functional properties relative to those of the unencapsulated drug or non-lipid associated drug. In addition, different liposomal or lipid-complex products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect the functional properties of these drug products.
Amphotericin B is a macrocyclic, polyene, antifungal antibiotic produced from a strain of Streptomyces nodosus. Amphotericin B is designated chemically as:
-33--1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclononatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid (CAS No. 1397-89-3).
Amphotericin B has a molecular formula of C47H73NO17 and a molecular weight of 924.09.
The structure of amphotericin B is shown below:
Disease-modifying antirheumatic drug
Disease-modifying antirheumatic drugs (DMARDs) is a category of drugs used in many autoimmune disorders to slow down disease progression. Their use was first propagated in rheumatoid arthritis (hence their name) but has come to include many other diseases, such as Crohn's disease, lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP), myasthenia gravis and various others.
Some of these drugs are also used in the treatment of ulcerative colitis which may not, strictly speaking, be an autoimmune disorder. (See List of Autoimmune Diseases.)
Some DMARDs are mild chemotherapeutics but use a side-effect of chemotherapy - immunosuppression - as its main therapeutical benefit.

# Members
- adalimumab
- azathioprine
- chloroquine and hydroxychloroquine (antimalarials)
- cyclosporine (Cyclosporin A)
- D-penicillamine
- etanercept
- gold salts (sodium aurothiomalate, auranofin)
- infliximab
- leflunomide
- methotrexate (MTX)
- minocycline (a tetracycline antibiotic)
- sulfasalazine (SSZ)

# Alternatives
When treatment with DMARDs fails, cyclophosphamide or steroid pulse therapy is often used to stabilise uncontrolled autoimmune disease. Some severe autoimmune diseases are being treated with bone marrow transplants in clinical trials, usually after cyclophosphamide therapy has failed.
nl:DMARD
Artemether lumefantrine microbiology

# Microbiology

## Mechanism of Action
Coartem Tablets, a fixed ratio of 1:6 parts of artemether and lumefantrine, respectively, is an antimalarial agent. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. The exact mechanism by which lumefantrine, exerts its antimalarial effect is not well defined. Available data suggest lumefantrine inhibits the formation of -hematin by forming a complex with hemin. Both artemether and lumefantrine were shown to inhibit nucleic acid and protein synthesis.

## Activity In Vitro and In Vivo
Artemether and lumefantrine are active against the erythrocytic stages of Plasmodium falciparum.

## Drug Resistance
Strains of P. falciparum with a moderate decrease in susceptibility to artemether or lumefantrine alone can be selected in vitro or in vivo, but not maintained in the case of artemether. The clinical relevance of such an effect is not known.
Arteriovenous malformations overview

# Overview
Arteriovenous malformation is a congenital disorder of the connections between veins and arteries in the vascular system. The genetic transmission patterns of AVM (if any) are unknown, and AVM is not generally thought to be an inherited disorder--unless in the context of a specific hereditary syndrome.

# Historical Perspective
Emmanuel, Luschka and Virchow first described arteriovenous malformations in the mid-1800s. Olivecrona performed the first surgical excision of an intracranial AVM in 1932.

# Pathophysiology
Arteries and veins are part of the human cardiovascular system. Normally, the arteries in the vascular system carry oxygen-rich blood at a relatively high pressure.  Structurally, arteries divide and sub-divide repeatedly, eventually forming a sponge-like capillary bed. Blood moves through the capillaries, giving up oxygen and taking up waste products from the surrounding cells. Capillaries successively join together, one upon the other, to form the veins that carry blood away at a relatively low pressure.  The heart acts to pump blood from the low pressure veins to the high pressure arteries.

# Epidemiology and Demographics
An estimated 300,000 people in the US have AVMs, of which 12% (approximately 36,000) will exhibit symptoms that differ greatly in severity.

# Diagnosis

## Symptoms
Symptoms of AVM vary according to the location of the malformation.  Roughly (88% -needs citation) AVM are asymptomatic; often the malformation is discovered as part of an autopsy or during treatment of an unrelated disorder (called in medicine an incidental finding), rarely its expansion or a micro-bleed from it, could cause epilepsy, deficit or elicit pain.

# Treatment

## Medical Therapy
Treatment for brain AVMs can be symptomatic, and patients should be followed by a neurologist for any seizures, headaches or focal deficits. AVM-specific treatment may also involve endovascular embolization, neurosurgery or radiation therapy. Embolization, that is, cutting off the blood supply to the AVM with coils or particles or glue introduced by a radiographically guided catheter, can be used in addition to either, but is rarely successful in isolation except for in smaller AVMs. The neurological risk of any such intervention is roughly 10%.

## Surgery
The Spetzler-Martin grading system developed at the Barrow Neurological Institute is utilized by neurosurgeons to determine operative versus nonoperative management of AVMs.

## Future or Investigational Therapies
Despite many years of research, the central question of whether to treat AVMs has not been answered. All treatments, whether involving surgery, radiation, or drugs, have risks and side-effects. Therefore, it might be better in some cases to avoid treatment altogether and simply accept a small risk of coming to harm from the AVM itself. This question is currently being addressed in clinical trials..
Thin ascending limb of loop of Henle

# Overview
As the filtrate passes back up the thin ascending limb of loop of Henle, the concentration of the surrounding medulla decreases. The thin ascending limb is not permeable to water, but it is permeable to ions.
Sodium ions (Na+) are passively transported down this concentration gradient, from the thin ascending limb into the medulla.

# Histology
As in the descending limb, the epithelium is low simple cuboidal.
Atovaquone dosage and administration

# Dosage and Administration

### Dosage
Prevention of PCP: Adults and Adolescents (13 to 16 Years)
The recommended oral dose is 1,500 mg (10 mL) once daily administered with a meal.
Treatment of Mild-to-Moderate PCP: Adults and Adolescents (13 to 16 Years)
The recommended oral dose is 750 mg (5 mL) administered with meals twice daily for 21 days (total daily dose 1,500 mg).
Note: Failure to administer MEPRON Suspension with meals may result in lower plasma atovaquone concentrations and may limit response to therapy (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

### Administration
Foil Pouch
Open pouch by removing tab at perforation and tear at notch. Take entire contents by mouth. Can be discharged into a dosing spoon or cup or directly into the mouth.
Bottle
SHAKE BOTTLE GENTLY BEFORE USING.
BH3 interacting-domain death agonist
The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

# Interactions
BID is a pro-apoptotic Bcl-2 protein containing only the BH3 domain. In response to apoptotic signaling, BID interacts with another Bcl-2 family protein, Bax, leading to the insertion of Bax into organelle membranes, primarily the outer mitochondrial membrane.  Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane.  This results in the release of cytochrome c and other pro-apoptotic factors (such as SMAC/DIABLO) from the mitochondria, often referred to as mitochondrial outer membrane permeabilization, leading to activation of caspases. This defines BID as a direct activator of Bax, a role common to some of the pro-apoptotic  Bcl-2 proteins containing only the BH3 domain.
The anti-apoptotic Bcl-2 proteins, including Bcl-2 itself, can bind BID and inhibit BID's ability to activate Bax. As a result, the anti-apoptotic Bcl-2 proteins may inhibit apoptosis by sequestering BID, leading to reduced Bax activation.
The expression of BID is upregulated by the tumor suppressor p53, and BID has been shown to be involved in p53-mediated apoptosis. The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BID. However, p53 also has a transcription-independent role in apoptosis. In particular, p53 interacts with Bax, promoting Bax activation and the insertion of Bax into the mitochondrial membrane.
The BH3 interacting-domain death agonist has been shown to interact with:
- ATR/ATRIP,
- BCL2,
- CASP2,
- CASP8,
- MCL1,  and
- RPA.

# Cleavage
Several reports have demonstrated that caspase-8, and its substrate BID, are frequently activated in response to certain apoptotic stimuli in a death receptor-independent manner. N-hydroxy-L-arginine (NOHA), a stable intermediate product formed during the conversion of L-arginine to nitric oxide activates caspase-8. Activation of caspase-8, and subsequent BID cleavage  participate in cytochrome-c mediated apoptosis. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mediated activation of caspase-9 via cytochrome-c release has been shown to result in the activation of caspase-8 and Bid cleavage. Aspirin and Curcumin (diferuloylmethane) too activate caspase-8 to cleave and translocated Bid, induced a conformational change in and translocation of Bax and cytochrome-c release.
Bacitracin dosage and administration

# Dosage and Administration
TO BE ADMINISTERED INTRAMUSCULARLY ONLY
Infant dose: For infants under 2500 grams  900 units/kg/24 hours in 2 or 3 divided doses. For infants over 2500 grams  1,000 units/kg/24 hours, in 2 or 3 divided doses. Intramuscular injections of the solution should be given in the upper outer quadrant of the buttocks, alternating right and left and avoiding multiple injections in the same region because of the transient pain following injection.
Preparation of Solutions  Should be dissolved in sodium chloride injection containing 2 percent procaine hydrochloride. The concentration of the antibiotic in the solution should not be less than 5,000 units per mL nor more than 10,000 units per mL.
Diluents containing parabens should not be used to reconstitute bacitracin; cloudy solutions and precipitate formation have occurred.
Reconstitution of the 50,000 unit vial with 9.8 mL of diluent will result in a concentration of 5,000 units per mL.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Barton Center for Diabetes Education
The Barton Center for Diabetes Education is an independent organization dedicated to the education of children living with diabetes and their families and caregivers through year-round programs.

# History
In 1921, on the 100th anniversary of the birth of humanitarian Clara Barton, the Women's National Missionary Association of the Universalist Church gained control of her birthplace and the land surrounding the property and created a "fresh air camp" for inner city youths in honor of their famous member.  Also in that year, insulin was discovered as a means to treat diabetes, children diagnosed with a disease that was once a death sentence were faced with the day-to-day care for the disease, as were their families.
In 1932, Elliott P. Joslin, pioneer in diabetes research, education, and care, teamed up with the Women's National Missionary Association of the Universalist Church to form the Clara Barton Birthplace Camp for girls.  This "hospital in the woods" was to be an "island of safety" for girls with diabetes where recreation and fun was combined with diabetes education.  The successes of the camp prompted the creation of the Elliott P. Joslin Camp for boys with diabetes, and the two camps became the most successful and largest programs of their kind.
Over time, the growth and success of the camps grew to the point where the Joslin Diabetes Center took over full control of the boy's camp, and in 1985 Clara Barton Camp became its own non-profit organization and focused on not only summer camping for girls, but also on year-round programs that include their families and friends as well.

# Summer Programs

## Residential Camp
Summer camp sessions for girls ages 6-17 that have been diagnosed with type 1 diabetes

## Day Camp
Day camp programs for children with diabetes throughout New England.

## Adventure Camp
Nature orientied outdoor camping program for children with diabetes.
Nevoid basal cell carcinoma syndrome
The Nevoid Basal Cell Carcinoma Syndrome (NBCCS) (also known as Basal Cell Nevus Syndrome,  Multiple Basal Cell Carcinoma Syndrome, Gorlin syndrome, or Gorlin-Goltz syndrome) is an inherited group of multiple defects involving the skin, nervous system, eyes, endocrine system, and bones.
First described in 1960, NBCCS is an autosomal dominant condition that can cause unusual facial appearances and a predisposition for skin cancer. The prevalence is reported to be 1 case per 56,000-164,000 population. Recent work in molecular genetics has shown NBCCS to be caused by mutations in the PTCH (patched) gene found on chromosome arm 9q. If a child inherits the defective gene from either parent, he or she will have the disorder.

# Incidence
About 750,000 new cases of sporadic basal cell carcinoma (BCC) occur each year in the United States. Ultraviolet (UV) radiation from the sun is the main trigger of these cancers, and people with fair skin are especially at risk. Most sporadic BCC arise in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. By comparison, one of the prime features of NBCCS is development of multiple BCC at an early age, often in the teen years.  Each person who has this syndrome is affected to a different degree, some having many more manifestations characteristic of it than others.

# Diagnostic criteria
Diagnosis of NBCCS is made by having 2 major criteria or 1 major and 2 minor criteria.
The major criteria consist of the following:
- more than 2 BCCs or 1 BCC in a person younger than 20 years;
- odontogenic keratocysts of the jaw
- 3 or more palmar or plantar pits
- calcification of the falx cerebri
- bifid, fused, or splayed ribs
- first-degree relative with NBCCS.
The minor criteria include the following:
- macrocephaly.
- congenital malformations, such as cleft lip or palate, frontal bossing, or hypertelorism.
- other skeletal abnormalities, such as Sprengel deformity, pectus deformity, or syndactyly.
- radiologic abnormalities, such as bridging of the sella turcica, vertebral anomalies, modeling defects or flame-shaped lucencies of hands and feet.
- ovarian fibroma or medulloblastoma.
People with NBCCS need education about the syndrome, and may need counseling and support, as coping with the multiple BCCs and multiple surgeries is often difficult.  They should reduce UV light exposure, to minimize the risk of BCC. They should also be advised that receiving Radiation therapy for their skin cancers may be contraindicated. They should look for symptoms referable to other potentially involved systems: the CNS, the genitourinary system, the cardiovascular system, and dentition.
Genetic counseling is advised for prospective parents, since one parent with NBCCS causes a 50% chance that their child will also be affected.

# Physical examination
- Nevoid basal cell carcinoma syndrome. With permission from Dermatology Atlas.
- Nevoid basal cell carcinoma syndrome. With permission from Dermatology Atlas.
- Nevoid basal cell carcinoma syndrome. With permission from Dermatology Atlas.
Congenital generalized lipodystrophy
Synonyms and keywords: BerardinelliSeip syndrome

# Overview
Congenital generalized lipodystrophy is a very rare autosomal recessive skin condition, characterized by an extreme paucity of fat in the subcutaneous tissues. Only 250 cases of the condition have been reported, so it is estimated that it occurs in 1 in 10 million people worldwide. 

# Presentation
Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disorder associating insulin resistance, absence of subcutaneous fat and muscular hypertrophy.  The condition presents itself in early childhood with accelerated linear growth , quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans will begin to present itself throughout the body - mainly in the neck, trunk, and groin.  The disorder also has characteristic features like hepatomegaly which arises from fatty liver and made lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism and hypertriglyceridemia. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension. This disorder is also associated with metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and the polycystic ovary syndrome can develop. This impairs fertility for the women, and only a few documented cases of successful pregnancies in women with BSCL exist. However, the fertility of men with the disorder is unaffected. 

# Diagnosis
Medical diagnosis of BSCL can be made after observing the physical symptoms of the disease: lipoatrophy affecting the trunk, limbs, and face; hepatomegaly; acromegaloid; insulin resistance; and high serum levels of triglycerides. Genetic testing can also confirm the disease, as mutations in the AGPAT2 and BSCL2 genes are indicative of the disease.

# Mechanism

## Congenital Generalized Lipodystrophy Type 1
In individuals with Type 1 CGL, the disorder is caused by a mutation at the AGPAT2 gene encoding 1-acylglycerol-3-phosphate O-acyltransferase 2 and located at 9q34.3. This enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, which is important in the biosynthesis of fats. This enzyme is highly expressed in adipose tissue, so it can be concluded that when the enzyme is defective in CGL, lipids cannot be stored in the adipose tissue. 

# Genetics

# Related Chapters
- Lipodystrophy
- Familial partial lipodystrophy
- List of cutaneous conditions
- Skin lesion
Boceprevir dosage and administration

# Dosage And Administration
VICTRELIS must be administered in combination with peginterferon alfa and ribavirin. The dose of VICTRELIS is 800 mg (four 200-mg capsules) three times daily (every 7 to 9 hours) with food  (see Table 1). Refer to the peginterferon alfa and ribavirin Package Inserts for instructions on dosing.
The following dosing recommendations differ for some subgroups from the dosing studied in the Phase 3 trials . Response-Guided Therapy (RGT) is recommended for most individuals, but longer dosing is recommended in targeted subgroups (e.g., patients with cirrhosis).

## VICTRELIS/Peginterferon alfa/Ribavirin Combination Therapy
Patients Without Cirrhosis Who Are Previously Untreated or Who Previously Failed Interferon and Ribavirin Therapy
Initiate therapy with peginterferon alfa and ribavirin for 4 weeks (Treatment Weeks 14).
Add VICTRELIS 800 mg (four 200-mg capsules) orally three times daily (every 7 to 9 hours) to peginterferon alfa and ribavirin regimen after 4 weeks of treatment. Based on the patient's HCV-RNA levels at Treatment Week (TW) 8, TW12 and TW24, use the following guidelines to determine duration of treatment (see Table 1).
Consideration should be given to treating previously untreated patients who are poorly interferon responsive (as determined at TW4) with 4 weeks peginterferon alfa and ribavirin followed by 44 weeks of VICTRELIS 800 mg orally three times daily (every 7 to 9 hours) in combination with peginterferon alfa and ribavirin in order to maximize rates of SVR.

## VICTRELIS/Peginterferon alfa/Ribavirin Combination Therapy: Patients with Cirrhosis
Patients with compensated cirrhosis should receive 4 weeks peginterferon alfa and ribavirin followed by 44 weeks VICTRELIS 800 mg (four 200-mg capsules) three times daily (every 7 to 9 hours) in combination with peginterferon alfa and ribavirin.

## Dose Modification
Dose reduction of VICTRELIS is not recommended.
If a patient has a serious adverse reaction potentially related to peginterferon alfa and/or ribavirin, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. Refer to the peginterferon alfa and ribavirin Package Inserts for additional information about how to reduce and/or discontinue the peginterferon alfa and/or ribavirin dose. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin. If peginterferon alfa or ribavirin is permanently discontinued, VICTRELIS must also be discontinued.

## Discontinuation of Dosing Based on Treatment Futility
Discontinuation of therapy is recommended in all patients with 1) HCV-RNA levels of greater than or equal to 100 IU per mL at TW12; or 2) confirmed detectable HCV-RNA levels at TW24.