Persius/hicric huggingface dataset:
Tobramycin clinical pharmacology

# Clinical Pharmacology
TOBI is specifically formulated for administration by inhalation. When inhaled, tobramycin is concentrated in the airways.

### Pharmacokinetics
TOBI contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes.(1) The bioavailability of TOBI may vary because of individual differences in nebulizer performance and airway pathology.(2) Following administration of TOBI, tobramycin remains concentrated primarily in the airways.
Sputum Concentrations: Ten minutes after inhalation of the first 300-mg dose of TOBI, the average concentration of tobramycin was 1237 g/g (ranging from 35 to 7417 g/g) in sputum. Tobramycin does not accumulate in sputum; after 20 weeks of therapy with the TOBI regimen, the average concentration of tobramycin at ten minutes after inhalation was 1154 g/g (ranging from 39 to 8085 g/g) in sputum. High variability of tobramycin concentration in sputum was observed. Two hours after inhalation, sputum concentrations declined to approximately 14% of tobramycin levels at ten minutes after inhalation.
Serum Concentrations: The average serum concentration of tobramycin one hour after inhalation of a single 300-mg dose of TOBI by cystic fibrosis patients was 0.95 g/mL. After 20 weeks of therapy on the TOBI regimen, the average serum tobramycin concentration one hour after dosing was 1.05 g/mL.
Elimination: The elimination half-life of tobramycin from serum is approximately 2 hours after intravenous (IV) administration. Assuming tobramycin absorbed following inhalation behaves similarly to tobramycin following IV administration, systemically absorbed tobramycin is eliminated principally by glomerular filtration. Unabsorbed tobramycin, following TOBI administration, is probably eliminated primarily in expectorated sputum.
Tolterodine detailed information
Tolterodine is an antimuscarinic drug that is used to treat urinary incontinence.  It is sold under the trade name Detrol.

# Pharmacology
Tolterodine acts on M2 and M3 subtypes of muscarinic receptors whereas most antimuscarinic treatments for overactive bladder only act on M3 receptors making them more selective.
Tolterodine, although it acts on two types of receptors, has fewer side effects than other antimuscarinics eg. oxybutynin (which is selective for M3 only) as tolterodine targets the bladder more than other areas of the body. This means that less drug needs to be given daily (due to efficient targeting of the bladder) and so there are fewer side effects.

# Side effects
Known Side Effects:
- Hyposalivation (Dry mouth)
- Decreased gastric motility (Upset stomach)
- Headache
- Constipation
- Dry eyes
- Sleepiness
Reports of Patients Experiences Since Detrol Became Available:
The following reactions have been reported in patients who have taken Detrol since it has become available:
- Allergic reactions including swelling
- Rapid heartbeat or abnormal heartbeat
- Accumulation of fluid in the arms and legs
- Hallucinations
Contraindications
Not to be used in patients with Myasthenia Gravis and Angle Closure Glaucoma
Topiramate indications and usage
For patient information about topiramate, click here.

# Indications and Usage

### Topiramate tablets USP are an antiepileptic (AED) agent indicated for:
Monotherapy epilepsy: Initial monotherapy in patients 10 years of age with partial onset or primary generalized tonic-clonic seizures.
Adjunctive therapy epilepsy: Adjunctive therapy for adults and pediatric patients (2 to 16 years of age) with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age with seizures associated with Lennox-Gastaut syndrome (LGS) .
- Topiramate is  most frequently prescribed for, the prevention of migraines. This drug is also widely used to treat migraines due to the effect it has on the blood vessels in the brain. It is used as a preventative for atypical migraine sufferers. It widens the blood vessels in the brain which become restricted by increased serotonin levels. It has been found to be increasingly effective for migraine sufferers with limited side effects.
- Bipolar disorder, and indicate that it may have mood stabilizing properties. In 2006, a Cochrane review concluded that there is insufficient evidence on which to base any recommendations regarding the use of topiramate in any phase of bipolar illness. Another meta-analysis published in the Lancet demonstrated that topiramate was of no significant benefit in the treatment of bipolar mania.
- Sometimes use topiramate to augment psychotropics, or to counteract the weight gain associated with numerous antidepressants.
- A more recent Cochrane review, published in 2010, suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder, however the authors note that this was based only on one randomized controlled trial and requires replication. Also the Authors noted that the long-term effects have not been studied.

### This drug has been investigated for use in:
- Treating alcoholism
- Methamphetamine addiction
- Obesity
- Reduce binge eating
- The drug is also used in clinical trials to treat post traumatic stress disorder.
- A pilot study suggested that topiramate is effective against infantile spasms.
- Topiramate as an effective treatment in the prevention of periventricular leukomalacia in preterm infants after an hypoxic-ischemic injury.

### Off-label and investigational uses
- Essential tremor
- Bulimia nervosa
- Obsessive-compulsive disorder
- Alcoholism
- Smoking cessation
- Idiopathic intracranial hypertension
- Cluster headache
- Treatment-resistant depression
- Cocaine dependence
- Topiramate is also being studied with a mixture of phentermine to form a drug called Qsymia for the treatment of obesity.
On May 21, 2010, Ortho-McNeil pled guilty and was fined $6.14 million by the FDA for promoting Topamax to treat psychiatric disorders without applying for any Federal government approval. Also, there were no data from any well-controlled clinical trial to demonstrate that Topamax was safe and/or effective to treat any psychiatric conditions at all.
Trimethylamine N-oxide reductase

# Overview
Trimethylamine N-oxide reductase (TOR or TMAO reductase, EC 1.7.2.3) is a microbial enzyme that can reduce trimethylamine N-oxide (TMAO) into trimethylamine (TMA), as part of the electron transport chain. The enzyme has been purified from E. coli and the photosynthetic bacteria Roseobacter denitrificans. Both the R. denitrificans and E. coli enzymes can accept electrons from cytochromes.
trimethylamine + 2 (ferricytochrome c)-subunit + H2O  trimethylamine N-oxide + 2 (ferrocytochrome c)-subunit + 2 H+
Trimethylamine oxide is found at high concentrations in the tissues of fish, and the bacterial reduction of this compound to foul-smelling trimethylamine is a major process in the spoilage of fish.
Tumor necrosis factor receptor 1
Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNF).

# Function
The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate the transcription factor NF-B, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor.

# Clinical significance
Germline mutations of the extracellular domains of this receptor were found to be associated with the human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS) or periodic fever syndrome.  Impaired receptor clearance is thought to be a mechanism of the disease.
Mutations in the TNFRSF1A gene is associated with elevated risk of multiple sclerosis.
Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are associated with more severe psychotic symptoms.
High serum levels is also associated with cognitive impairment and dementia.

# Interactions
TNFRSF1A has been shown to interact with:
- BAG4,
- CASP10,
- FADD,
- IKK2,
- JAK1,
- JAK2,
- PIP4K2B,
- PSMD2,
- RIPK1,
- SUMO1,
- TRADD
- TRAF2,
- TRPC4AP,
- TNF,  and
- UBE2I.
UK statutory notification system

# Overview
The UK statutory notification system for infectious diseases is a system whereby doctors are required to notify a "Proper Officer" of the local authority (such as a Consultant in Communicable Disease Control) if they are presented with a case of a serious infectious disease such as diphtheria or measles. The Proper Officer then sends a report to the Centre for Infections of the Health Protection Agency in Colindale,London.
The main purpose of the system is the detection and intervention in possible epidemics. It also enables surveillance data to be collected that can help in planning ways to prevent future outbreaks.

# History of the statutory notification system
The statutory requirement for the notification of certain infectious diseases first came into being in London in 1891. Cholera, diphtheria, smallpox and typhoid had to be reported by the head of the family or the landlord to the local authority. The system spread to the rest of England and Wales in 1899.
Originally, disease statistics were collected from the local authorities by the Registrar General's Office, where national statistics were already collected on births, marriages and deaths. This office was later known as the Office of Population Censuses and Surveys and is now called the Office for National Statistics. In 1997, however, the responsibility for administering the system was transferred to the CDSC.

# The system today
The main concern of the modern system is speed in detecting possible outbreaks, and accuracy of diagnosis is only secondary. Since 1968 clinical suspicion of a notifiable infection is all that is required to report a case of a disease. The attending doctor must notify the proper officers, who are usually consultants in communicable disease control. These consultants are required to inform the CDSC on a weekly basis of each case of a disease that has been notified. The CDSC collates these reports and publishes its analysis of local and national trends.
The list of notifiable diseases now stands at 30, including leprosy, which must be reported directly to the director of the CDSC. During the 2002-3 outbreak, SARS was added to the list as a 31st.
Selected notifiable diseases:
- Anthrax
- Cholera
- Dysentery
- Food poisoning
- Malaria
- Measles
- Meningitis
- Mumps
- Plague
- Polio
- Rabies
- Rubella
- Scarlet fever
- Smallpox
- Tetanus
- Tuberculosis
- Typhoid fever
- Typhus fever
- Viral hepatitis
- Whooping cough
VOC contamination of groundwater
VOCs (volatile organic compounds) are a dangerous contaminant of groundwater.  They are generally introduced to the environment through careless industrial practices.

# Overview
VOCs are responsible for a number of adverse health effects especially for nursing and pregnant mothers.  Many of these compounds were not known to be harmful until the late 1960s and it was some time before regular testing of groundwater identified these substances in drinking water sources.

# Specific VOCs

## PCE
Tetrachloroethylene is used in metal degreasing and dry cleaning.  It is generally harmless to adults.

## TCE
Trichloroethylene is used in cleaning metal parts and was widely believed to be harmless before being linked to birth defects.

## Toluene
Toluene is an organic compound which is mostly harmless to adults and is sometimes abused as an inhalant.  Fetal Toluene Syndrome has been defined and resembles Fetal Alcohol Syndrome with resultant birth defects, but the U.S. Centers for Disease Control and Prevention have identified differentiating features between the two syndromes including FTS havinng the additional facial features of micrognathia, large anterior fontanel, down-turned mouth  corners, hair patterning abnormalities, bifrontal narrowing of the face, and ear abnormalities.

# History

## Camp Lejeune
U.S. Marine Corps Base Camp Lejeune was built near Jacksonville, North Carolina in 1942.  In 1982, the Marine Corps discovered volatile organic compounds (VOCs) in several drinking water wells that fed into two of the eight water systems.  The sources were traced to Tetrachloroethylene (PCE) from a dry cleaner off the base and Trichloroethylene which had been used in vehicle maintenance on the base.  These problems were addressed but there were concerns with nursing and pregnant mothers who may have been exposed previously.  It wasn't until the late 1990s that the federal government tried to track down people who may have been exposed.

## Love Canal
Love Canal was an abandoned canal near Niagara Falls, New York which was used by the U.S. military and Occidental Petroleum as a chemical waste dumping ground.  Numerous cases of cancer and birth defects were found from the 1950s to the 1970s.  The primary VOC at Love Canal is toluene, which is found along with dioxins and other pollutants.
Vaginismus (patient information)
For the WikiDoc page for this topic, click here

# Overview
Vaginismus is an involuntary spasm of the muscles surrounding the vagina. The spasms close the vagina.

# What are the symptoms of Vaginismus?
- Vaginal penetration during sex is difficult or impossible.
- Vaginal pain is common during sexual intercourse or an attempted pelvic exam.

# What causes Vaginismus?
- Vaginismus is considered a disorder of sexual dysfunction. It has several possible causes, including past sexual trauma or abuse, psychological factors, or a history of discomfort with sexual intercourse. Sometimes no cause can be found.
- Vaginismus is an uncommon condition. The exact number of women who have this problem is unknown.
- Women with varying degrees of vaginismus often develop anxiety regarding sexual intercourse. The condition causes penetration to be difficult and painful, or even impossible. However, this does not mean the woman cannot become sexually aroused. Many women may have orgasms when the clitoris is stimulated.

# When to seek urgent medical care?
If you have pain associated with intercourse or difficulties with successful vaginal penetration, contact your health care provider.

# Diagnosis
- A pelvic exam can confirm the diagnosis of vaginismus.
- A medical history and complete physical exam is important to rule out other causes of pain with sexual intercourse.

# Treatment options
- Treatment involves extensive therapy that combines education, counseling, and behavioral exercises. Such exercises include pelvic floor muscle contraction and relaxation (Kegel exercises).
- Vaginal dilation exercises are recommended using plastic dilators. This should be done under the direction of a sex therapist or other health care provider. Such therapy should involve the partner, and can gradually include more intimate contact, ultimately resulting in intercourse.
- Educational resources should be provided. This includes information about sexual anatomy, physiology, the sexual response cycle, and common myths about sex.

# Where to find medical care for Vaginismus?
Directions to Hospitals Treating Vaginismus

# What to expect (Outlook/Prognosis)?
When treated by a specialist in sex therapy, success rates are generally very high.

# Possible complications
Vaginismus may lead to unsatisfying sex activity and tension in intimate relationships.

# Source
Vancomycin clinical pharmacology
In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, mean plasma concentrations of about 19 mcg/mL 2 hours after infusion, and mean plasma concentrations of about 10 mcg/mL 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.
The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. Renal dysfunction slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution coefficient is from 0.3 to 0.43 L/kg. There is no apparent metabolism of the drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in 6 hours. Serum concentrations of about 10 mcg/mL are achieved by intraperitoneal injection of 30 mg/kg of vancomycin. However, the safety and efficacy of the intraperitoneal use of vancomycin has not been established in adequate and well-controlled trials (see PRECAUTIONS).
Total systemic and renal clearance of vancomycin may be reduced in the elderly.
Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After IV administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.
Vancomycin indications and usage
Vancomycin is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin is indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly.
Vancomycin is effective in the treatment of staphylococcal endocarditis. Its effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin and skin structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures.
Vancomycin has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by Streptococcus viridans or S. bovis. For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin has been reported to be effective only in combination with an aminoglycoside.
Vancomycin has been reported to be effective for the treatment of diphtheroid endocarditis. Vancomycin has been used successfully in combination with either rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids.
Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to vancomycin.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin and other antibacterial drugs, vancomycin 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.
Viral hemorrhagic fever overview

# Overview
The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by five distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae, Togaviridae, and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, whilst others, such as the African Ebola virus, can cause severe, life-threatening disease.

# Treatment

## Secondary Prevention
In conjunction with the World Health Organization, CDC has developed practical, hospital-based guidelines, titled Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting.  The manual can help health-care facilities recognize cases and prevent further hospital-based disease transmission using locally available materials and few financial resources.

## Future or Investigational Therapies
Scientists and researchers are challenged with developing containment, treatment, and vaccine strategies for these diseases. Another goal is to develop immunologic and molecular tools for more rapid disease diagnosis, and to study how the viruses are transmitted and exactly how the disease affects the body (pathogenesis). A third goal is to understand the ecology of these viruses and their hosts in order to offer preventive public health advice for avoiding infection.
WiedemannRautenstrauch syndrome

# Overview
WiedemannRautenstrauch (WR) syndrome Template:IPA-de, also known as neonatal progeroid syndrome, is an autosomal recessive progeroid syndrome.
WR was first reported by Rautenstrauch and Snigula in 1977; and the earliest reports made subsequently have been by Wiedemann in 1979, by Devos in 1981, and Rudin in 1988. There has been over 30 cases of WR.
WR is associated with abnormalities in bone maturation, and lipids and hormone metabolism. Affected individuals exhibit intrauterine and postnatal growth retardation, leading to short stature and an aged appearance from birth. They have physical abnormalities including a large head (macrocephaly), sparse hair, prominent scalp veins, inward-folded eyelid (entropion), widened anterior fontanelles, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin (lipoatrophy), delayed tooth eruption, abnormal hair pattern (hypotrichosis), beaked nose, mild to severe mental retardation and dysmorphism.
Zidovudine indications and usage

# Indications And Usage

## Treatment of HIV-1
RETROVIR, a nucleoside reverse transcriptase inhibitor, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

## Prevention of Maternal-Fetal HIV-1 Transmission
RETROVIR is indicated for the prevention of maternal-fetal HIV-1 transmission . The indication is based on a dosing regimen that included 3 components:
1.antepartum therapy of HIV-1 infected mothers
2.intrapartum therapy of HIV-1 infected mothers
3.post-partum therapy of HIV-1 exposed neonate.
Points to consider prior to initiating RETROVIR in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:
- In most cases, RETROVIR for prevention of maternal-fetal HIV-1 transmission should be given in combination with other antiretroviral drugs.
- Prevention of HIV-1 transmission in women who have received RETROVIR for a prolonged period before pregnancy has not been evaluated.*Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of therapy with RETROVIR during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of antiretroviral therapy for their own health may consider delaying use; this indication is based on use after 14 weeks gestation.