Persius/hicric huggingface dataset:
Lethal congenital contracture syndrome

# Overview
Lethal congenital contracture syndrome 1 (LCCS1), also called Multiple contracture syndrome, Finnish type, is an autosomal recessive genetic disorder characterized by total immobility of a fetus, detectable at around the 13th week of pregnancy. LCCS1 invariably leads to prenatal death before the 32nd gestational week. LCCS1 is one of 40 Finnish heritage diseases. It was first described in 1985 and since then, approximately 70 cases have been diagnosed.

# Characteristics
LCCS1 is characterized by total lack of the movements of the fetus, and is detectable at 13th week of pregnancy. It is accompanied by oedema, small chin, small lungs, crooked joints and occasional skin webs of the neck and elbows. The fetus has characteristic pattern of malpositions recognizable even in severely macerated fetuses with club feet and hyperextension of the knees but the elbows and wrists showing flexion contractures.
Neuropathological analysis shows lack of anterior horn motoneurons and severe atrophy of the ventral spinal cord. The skeletal muscles are severely hypoplastic.

# Cause
The defective gene associated with LCCS1 is mRNA export mediator GLE1 at chromosome 9q34. In more than 40 families the fetus has been homozygous for A->G substitution (c.432-10A>G) located in intron 3 of GLE1 creating an illegitimate splice acceptor site resulting in nine extra nucleotides in the GLE1 cDNA (GLE1 FinMajor mutation). In one family the fetus has been compound heterozygous for GLE1 FinMajor and RH substitution in exon 12.
A slightly milder phenotype with survival beyond 32nd gestational week also characterized by foetal akinesia, arthrogryposis and anterior horn cell loss (Lethal arthrogryposis with anterior horn cell disease, LAAHD) was also shown to be allelic to LCCS1 and result from mutations in GLE1.

# Genetics
File:Autorecessive.svg
LCCS1 is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder (GLE1) is located on an autosome (chromosome 9), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

## Population genetics
LCCS1 belongs to Finnish heritage of diseases and cases have been confirmed until now (2009) only in Finland. The prevalence is 1 in 25000 births. The carrier frequency is 1% in whole Finland and 2% in North-Eastern part of Finland where the birthplaces of ancestors of affected individual show clustering.

## Mapping
Makela-Bengs et al. (1997,1998)  performed a genome-wide screening and linkage analysis and assigned the LCCS locus to a defined region of 9q34.
Luliconazole dosage and administration

# Dosage and Administration
For topical use only. LUZU Cream, 1% is not for ophthalmic, oral, or intravaginal use.
When treating interdigital tinea pedis, a thin layer of LUZU Cream, 1% should be applied to the affected area and approximately 1 inch of the immediate surrounding area(s) once daily for two (2) weeks.
When treating tinea cruris or tinea corporis, LUZU Cream, 1% should be applied to the affected area and approximately 1 inch of the immediate surrounding area(s) once daily for one (1) week.
Melanin-concentrating hormone receptor
Two Melanin-concentrating hormone receptors (MCHR) have recently been characterized: MCH-R1 and MCH-R2. These two receptors share approximately 38% homology.
- MCH-R1 is expressed in all mammals.
- MCH-R2 is only found in some primates and carnivores including dogs, ferrets and humans.

# Clinical significance
Antagonists might be useful in the treatment of obesity and anxiety and depression.  An agonist might have possible utility as a treatment for osteoporosis and insomnia
Research is ongoing for antagonists affecting MCH receptors R1 and R2.
Macrophage migration inhibitory factor
Macrophage migration inhibitory factor (MIF or MMIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the MIF gene. MIF is an important regulator of innate immunity.
Bacterial antigens stimulate white blood cells to release MIF into the blood stream. The circulating MIF binds to CD74 on other immune cells to trigger an acute immune response. Hence, MIF is classified as an inflammatory cytokine. Furthermore, glucocorticoids also stimulate white blood cells to release MIF and hence MIF partially counteracts the inhibitory effects that glucocorticoids have on the immune system. Finally trauma activates the anterior pituitary gland to release MIF.

# Structure
Macrophage migration inhibitory factor assembles into a trimer composed of three identical subunits.  Each of these monomers contain two antiparallel alpha helices and a four-stranded beta sheet.  The monomers surround a central channel with 3-fold rotational symmetry.

# Enzymatic activity
MIF contains two motifs with catalytic activity. The first is a 27 amino acid motif located at the N-terminus functions as a phenylpyruvate tautomerase that can catalyze the conversion of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). MIF also contains a Cys-Ala-Leu-Cys catalytic site between residues 57 and 60 that appears to function as a disulfide reductase.

# Function
This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. MIF plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate a role in integrin signaling pathways.

# Mechanism of action
MIF binds to CD74, inducing its phosphorylation and the recruitment of CD44 which then activates non-receptor tyrosine kinases, leading ultimately to extracellular signal-regulated kinase phosphorylation.

# Interactions
Macrophage migration inhibitory factor has been reported to interact with:
- BNIPL,
- CD74,
- COPS5,
- CXCR4, and
- RPS19.

# Clinical significance
MIF is an inflammatory mediator associated with rheumatoid arthritis (RA) severity. MIF protein levels are increased in the plasma of people with schizophrenia, including people in the early stages of the illness, but the clinical significance of this has not been determined. Macrophage migration inhibitory factor is also a potential drug target for sepsis, rheumatoid arthritis, and cancer. It has also been shown to induce changes in the heart during sepsis.
Evidence suggests that there is a correlation between MIF production and metastatic potential in colorectal cancer.
It has been reported that there is increased MIF production in Alzheimer's disease and mild cognitive impairment. It has further been reported that this enzyme, in Alzheimer's disease, undergoes glycation and oxidation, inhibiting its activity.
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Methysergide dosage and administration

# Dosage and Administration
Usual adult dose 4-8 mg daily. Tablets to be given with meals.
Note:      There must be a medication-free interval of 3-4 weeks after every 6-month course of treatment. (See WARNINGS)
No pediatric dosage has been established.
If, after a 3-week trial period, efficacy has not been demonstrated, longer administration of Sansert (methysergide maleate) is unlikely to be of benefit.
Metipranolol dosage and administration

# Dosage and Administration
The recommended dose is one drop of metipranolol ophthalmic solution in the affected eye(s) twice a day.
If the patient's IOP is not at a satisfactory level on this regimen, use of more frequent administration or a larger dose of metipranolol ophthalmic solution is not known to be of benefit. Concomitant therapy to lower intraocular pressure can be instituted.
In clinical trials, metipranolol ophthalmic solution was safely used during concomitant therapy with pilocarpine, epinephrine, or acetazolamide.
Minocycline hydrochloride how supplied

# How Supplied
DYNACIN (MINOCYCLINE HCl CAPSULES, USP) equivalent to 50 mg minocycline are opaque white capsules imprinted "0487" and "DYNACIN 50 mg" and are supplied as follows:
NDC 99207-487-10        Bottles of 100
NDC 99207-487-11        Bottle of 1000.
DYNACIN (MINOCYCLINE HCl CAPSULES, USP) equivalent to 75 mg minocycline are light gray opaque capsules imprinted "0489" and "DYNACIN 75 mg" and are supplied as follows:
NDC 99207-489-10        Bottles of 100
NDC 99207-489-11        Bottle of 1000.
DYNACIN (MINOCYCLINE HCl CAPSULES, USP) equivalent to 100 mg minocycline are opaque dark gray and opaque white capsules imprinted "0488" and "DYNACIN 100 mg" and are supplied as follows:
NDC 99207-488-05        Bottles of 50
NDC 99207-488-11        Bottle of 1000.
Dispense in tight, light-resistant container with child-resistant closure.
Store at 20o25oC (68o77oF). .
Protect from light, moisture and excessive heat.
Mitral Regurgitation 2D Echocardiology

# Aetiology and morphological features in 2-D Echocardiography

## Rheumatic Mitral regurgitation
In rheumatic mitral regurgitation, there is some degree of commissural fusion and thickening of the tips visible in 2 dimensional echocardiography. The movement of the valve leaflets is restricted.

## Myxomatous mitral valve
The leaflets and chordae are thick and reduntant. Reduced tensile strength leads to progressive elongation or rupture of chordae. Ruptured chordae appear as flail segments. To diagnose mitral valve prolapse, the following criteria should be fulfilled during echocardiography - Movement of any part of either leaflet more than 2mm behind the annular plane in parasternal long axis view and movement of point of co-aptation behind the annular plane in apical 4 chamber view.

## Annular calcification
Mitral annulus is usually smaller in systole. The increased rigidity due to annular calcification impairs contraction. In 2D- echocardiography, there is increased echogenicity on the LV side immediately adjacent to the attachment of the posterior mitral valve leaflet. Region of anterior mitral leaflet is only rarely involved. This is common in elderly subjects and younger ones with chronic renal failure and hypertension.

## Ischaemic mitral regurgitation
Mitral regurgitation can occur in ischemia as a result of regional left ventricular dysfunction with abnormal contraction of papillary muscle or underlying ventricular wall. Myocardial infarction can result in MR at rest while if the underlying cause is ischemia the MR may be intermittent. The echocardiogram is characterized by restricted valve leaflet motion and tenting of mitral valve in systole.

## Papillary muscle rupture
This is usually a complication of myocardial infarction. If entire papillary muscle is disconnected from the left ventricle severe MR results and few survive. Partial rupture is more common.

## Functional mitral regurgitation
Functional MR results due to LV dilatation and systolic dysfunction in those with a structurally normal mitral valve apparatus.
Nafcillin sodium clinical pharmacology

# Clinical Pharmacology
In a study of five healthy adults administered a single 500 mg dose of nafcillin by intravenous injection over seven minutes, the mean plasma concentration of the drug was approximately 30 mcg/mL at 5 minutes after injection. The mean area under the plasma concentration-versus-time curve (AUC) for nafcillin in this study was 18.06 mcgh/mL.
The serum half-life of nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.
In contrast to the other penicillinase-resistant penicillins, only about 30% of nafcillin is excreted as unchanged drug in the urine of normal volunteers, and most within the first six hours. Nafcillin is primarily eliminated by nonrenal routes, namely hepatic inactivation and excretion in the bile.
Nafcillin binds to serum proteins, mainly albumin. The degree of protein binding reported for nafcillin is 89.9  1.5%. Reported values vary with the method of study and the investigator.
The concurrent administration of probenecid with nafcillin increases and prolongs plasma concentrations of nafcillin. Probenecid significantly reduces the total body clearance of nafcillin with renal clearance being decreased to a greater extent than nonrenal clearance.
The penicillinase-resistant penicillins are widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids. With normal doses insignificant concentrations are found in the aqueous humor of the eye. High nafcillin CSF levels have been obtained in the presence of inflamed meninges.
Renal failure does not appreciably affect the serum half-life of nafcillin; therefore, no modification of the usual nafcillin dosage is necessary in renal failure with or without hemodialysis. Hemodialysis does not accelerate the rate of clearance of nafcillin from the blood.
A study which assessed the effects of cirrhosis and extrahepatic biliary obstruction in man demonstrated that the plasma clearance of nafcillin was significantly decreased in patients with hepatic dysfunction. In these patients with cirrhosis and extrahepatic obstruction, nafcillin excretion in the urine was significantly increased from about 30 to 50% of the administered dose, suggesting that renal disease superimposed on hepatic disease could further decrease nafcillin clearance.
Nafcillin sodium indications and usage

# Indications and Usage
Nafcillin for injection, USP is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Culture and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug.
Nafcillin for injection, USP may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results. Nafcillin for injection, USP should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to an organism other than a resistant Staphylococcus, therapy should not be continued with nafcillin for injection, USP.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of nafcillin for injection, USP and other antibacterial drugs, nafcillin for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
National Center for Research Resources

# Overview
The National Center for Research Resources or NCRR, is a United States government agency.  NCRR provides funding to laboratory scientists and researchers for facilities and tools in the goal of curing and treating diseases.

# Organization and history
The National Center for Research Resources (NCRR) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH) within the Department of Health and Human Services of the federal government of the United States. The NIH is one of eight agencies under the Public Health Service (PHS) in the Department of Health and Human Services (DHHS).
In 1990 the Division of Research Resources and the Division of Research Services were merged to form the National Center for Research Resources.  Its mission statement declares that it "provides laboratory scientists and clinical researchers with environments and tools that they can use to prevent, detect, and treat a wide range of diseases."

# Role
NCRR administers, fosters, and supports the development of research resources for health-related research. Programs are carried out through: (a) research grants, research and development contracts, and individual and institutional research training awards; (b) cooperation and collaboration with organizations and institutions engaged in multi-categorical research resources activities; and (c) collection and dissemination of information on research and findings in these areas.
The NCRR funds research concentrated in four programmatic Divisions: Division for Biomedical Technology Research and Research Resources, Division for Clinical Research Resources, Division of Comparative Medicine, and Division of Research Infrastructure.
NCRR's Major Extramural Programs include:
Division for Biomedical Technology Research and Research Resources
- Biomedical Technology (BT) Resource Centers
- Biomedical Informatics Research Network (BIRN)
- Shared Instrumentation Grant (SIG)
- High-End Instrumentation (HEI)
Division for Clinical Research Resources
- Clinical and Translational Science Awards
- General Clinical Research Centers (GCRCs)
- National Gene Vector Laboratories (NGVLs)
- Rare Diseases Clinical Research Network
- Islet Cell Resource (ICR) Centers
- Human Tissues and Organs Resource
- Science Education Partnership Award (SEPA)
Division of Comparative Medicine
- National Primate Research Centers (NPRCs)
- Laboratory Animal Sciences (LAS)
- Animal Models
- Biological Models and Materials Research (BMMR)
- NIH Chimpanzee Management Program
Division of Research Infrastructure
- Research Centers in Minority Institutions (RCMI)
- Institutional Development Award (IDeA)
- Research and Animal Facilities Improvements (RFI and AFI)
Nitazoxanide dosage and administration

# Dosage And Administration
DIRECTIONS FOR MIXING ALINIA FOR ORAL SUSPENSION
Prepare a suspension at time of dispensing as follows: The amount of water required for preparation of the suspension is 48 mL. Tap bottle until all powder flows freely. Add approximately one-half of the total amount of water required for reconstitution and shake vigorously to suspend powder. Add remainder of water and again shake vigorously.
The container should be kept tightly closed, and the suspension should be shaken well before each administration. The suspension may be stored for 7 days, after which any unused portion must be discarded.
A single Alinia tablet contains a greater amount of nitazoxanide than is recommended for pediatric dosing and should therefore not be used in pediatric patients 11 years or younger.
Oxacillin sodium clinical pharmacology

# Clinical Pharmacology
Intravenous administration provides peak serum levels approximately 5 minutes after the injection is completed.  Slow I.V. administration of 500 mg gives a peak serum level of 43 mcg/mL after 5 minutes with a half-life of 20 to 30 minutes.
The penicillinase-resistant penicillins bind to serum protein, mainly albumin. The degree of protein binding reported for oxacillin is 94.2%  2.1%. Reported values vary with the method of study and the investigator.
The penicillinase-resistant penicillins vary in the extent to which they are distributed in the body fluids.  With normal doses, insignificant concentrations are found in the cerebrospinal fluid and aqueous humor.  All the drugs in this class are found in therapeutic concentrations in the pleural, bile, and amniotic fluids.
The penicillinase-resistant penicillins are rapidly excreted primarily as unchanged drug in the urine by glomerular filtration and active tubular secretion. The elimination half-life for oxacillin is about 0.5 hours.  Nonrenal elimination includes hepatic inactivation and excretion in bile.
Probenecid blocks the renal tubular secretion of penicillins. Therefore, the concurrent administration of probenecid prolongs the elimination of oxacillin and, consequently, increases the serum concentration.
Intramuscular injections give peak serum levels 30 minutes after injection.  A 250 mg dose gives a level of 5.3 mcg/mL while a 500 mg dose peaks at 10.9 mcg/mL.  Intravenous injection gives a peak about 5 minutes after the injection is completed.  Slow I.V. dosing with 500 mg gives a 5 minute peak of 43 mcg/mL with a half-life of 20 to 30 minutes.
Oxacillin sodium indications and usage

# Indications and Usage
Oxacillin is indicated in the treatment of infections caused by penicillinase producing staphylococci which have demonstrated susceptibility to the drug. Cultures and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug.
Oxacillin may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results.  Oxacillin should not be used in infections caused by organisms susceptible to penicillin G.  If the susceptibility tests indicate that the infection is due to an organism other than a resistant Staphylococcus, therapy should not be continued with oxacillin.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Oxacillin for Injection, USP and other antibacterial drugs, Oxacillin for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.  When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.  In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Peripherally inserted central catheter

# Overview
A peripherally inserted central catheter (PICC or PIC line) is a form of intravenous access that can be used for a prolonged period of time, e.g. for long chemotherapy regimens, extended antibiotic therapy or total parenteral nutrition. First described in 1975, it is an alternative to  subclavian lines, internal jugular lines or femoral lines which have higher rates of infection. Subclavian and internal jugular line placements may result in pneumothorax (air in the pleural space of lung).
A PICC is inserted in a peripheral vein, such as the cephalic vein, basilic vein, or brachial vein and then advanced through increasingly larger veins, toward the heart until the tip rests in the distal superior vena cava or cavo-atrial junction.
PICCs are usually inserted by radiologists, physician assistants, radiologist assistants, or certified registered nurses using ultrasound, chest radiographs and fluoroscopy to aid in their insertion and to confirm placement. Complications may include catheter occlusion, phlebitis, hemorrhage, thrombosis and infection. Urokinase may be used to lyse obstructions. PICC lines generally will remain in place no longer than 30 days, although duration of use varies from just a few days in patients requiring short courses of chemotherapy or biotherapy to a year for patients requiring longer treatment. Commonly, other forms of intravenous access are considered if the treatment course is protracted.  While replacement is generally considered a year post-insertion, patients have survived with the same PICC in situ for several years without complication.
Certain types of PICCs have recently been approved by the FDA for use in power injection.  These PICCs, often referred to as "POWER PICCs", are designed to withstand the high pressures associated with radiocontrast studies.

# Notes
-  Hoshal VL. Total intravenous nutrition with peripherally inserted silicone elastomer central venous catheters. Arch Surg 1975;43:193743. PMID 805577.