Gastroesophageal reflux disease(GERD)

Gastroesophageal reflux disease (American English and Canadian English) or Gastro-oesophageal reflux disease (British English, Hiberno-English, Australian English, New Zealand English, South African English) and abbreviated to either GERD or GORD is defined as chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus.

This is commonly due to transient or permanent changes in the barrier between the esophagus and the stomach. This can be due to incompetence of the cardia, transient cardia relaxation, impaired expulsion of gastric reflux from the esophagus, or a hiatus hernia.



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Symptoms
Adults

Heartburn is the major symptom of acid in the esophagus, characterized by burning discomfort behind the breastbone (sternum). Findings in GERD include esophagitis (reflux esophagitis) — inflammatory changes in the esophageal lining (mucosa) —, strictures, difficulty swallowing (dysphagia), and chronic chest pain. Patients may have only one of those symptoms. Typical GERD symptoms include cough, hoarseness, voice changes, chronic ear ache, burning chest pains, nausea or sinusitis. GERD complications include stricture formation, Barrett's esophagus, esophageal spasms, esophageal ulcers, and possibly even lead to esophageal cancer, especially in adults over 60 years old.

Occasional heartburn is common but does not necessarily mean one has GERD. Patients with heartburn symptoms more than once a week are at risk of developing GERD. A hiatal hernia is usually asymptomatic, but the presence of a hiatal hernia is a risk factor for developing GERD.

Children

GERD may be difficult to detect in infants and children. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems. Inconsolable crying, failure to gain adequate weight, refusing food, bad breath, and belching or burping are also common. Children may have one symptom or many — no single symptom is universal in all children with GERD.

It is estimated that of the approximately 4 million babies born in the U.S. each year, up to 35% of them may have difficulties with reflux in the first few months of their life. Most of those children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition.

Babies' immature digestive systems are usually the cause, and most infants stop having acid reflux by the time they reach their first birthday. Some children do not outgrow acid reflux, however, and continue to have it into their teen years. Children who have had heartburn that does not seem to go away, or any other GERD symptoms for a while, should talk to their parents and visit their doctor.


Diagnosis
A detailed history taking is vital to the diagnosis. Useful investigations may include barium swallow X-rays, esophageal manometry, 24-hour esophageal pH monitoring and Esophagogastroduodenoscopy (EGD). In general, an EGD is done when the patient does not respond well to treatment, or has alarm symptoms including: dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate once-in-a-lifetime endoscopy for patients with longstanding GERD, to evaluate the possible presence of Barrett's esophagus, a precursor lesion for esophageal adenocarcinoma.

Esophagogastroduodenoscopy (EGD) (a form of endoscopy) involves insertion of a thin scope through the mouth and throat into the esophagus and stomach (often while the patient is sedated) in order to assess the internal surfaces of the esophagus, stomach, and duodenum.

Biopsies can be performed during gastroscopy and these may show:

  • Edema and basal hyperplasia (non-specific inflammatory changes)
  • Lymphocytic inflammation (non-specific)
  • Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
  • Eosinophilic inflammation (usually due to reflux)
  • Goblet cell intestinal metaplasia or Barretts esophagus.
  • Elongation of the papillae
  • Thinning of the squamous cell layer
  • Dysplasia or pre-cancer.
  • Carcinoma.

Reflux changes may be non-erosive in nature, leading to the entity non-erosive reflux disease.

What is Gout


Gout is caused by buildup of uric acid,Uric acid crystalls travel and accumulate in the joints,in specially in feet and legs causing pain in the legs,crystals of monosodium urate or uric acid are deposited on the articular cartilage of joints, tendons and surrounding tissues. These crystals cause inflammation and pain, both severe. If unchecked, the crystals form tophi, which can cause significant tissue damage. Gout results from a combination of elevated concentrations of uric acid and overall acidity in the bloodstream. In isolation, neither elevated uric acid (hyperuricemia) nor acidity is normally sufficient to cause gout.

  Subscribe in a reader Signs and symptoms
Gout is characterized by excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected joint. This occurs commonly in men in their toes but can appear in other parts of the body and affects women as well. Low-grade fever may also be present. The patient usually suffers from two sources of pain. The crystals inside the joint cause intense pain whenever the affected area is moved. The inflammation of the tissues around the joint also causes the skin to be swollen, tender and sore if it is even slightly touched. For example, a blanket or even the lightest sheet draping over the affected area could cause extreme pain.
Gout usually attacks the big toe (approximately 75 percent of first attacks); however, it also can affect other joints such as the ankle, heel, instep, knee, wrist, elbow, fingers, and spine. In some cases, the condition may appear in the joints of small toes that have become immobile due to impact injury earlier in life, causing poor blood circulation that leads to gout.

Hernia Repair animation


It is generally advisable to repair hernias in a timely fashion, in order to prevent complications such as organ dysfunction, gangrene, and multiple organ dysfunction syndrome. Most abdominal hernias can be surgically repaired, and recovery rarely requires long-term changes in lifestyle. Uncomplicated hernias are principally repaired by pushing back, or "reducing", the herniated tissue, and then mending the weakness in muscle tissue (an operation called herniorrhaphy). If complications have occurred, the surgeon will check the viability of the herniated organ, and resect it if necessary. Modern muscle reinforcement techniques involve synthetic materials (a mesh prosthesis) that avoid over-stretching of already weakened tissue (as in older, but still useful methods). The mesh is placed over the defect, and sometimes staples are used to keep the mesh in place. Evidence suggests that this method has the lowest percentage of recurrences and the fastest recovery period. Increasingly, some repairs are performed through laparoscopes.

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Many patients are managed through day surgery centers, and are able to return to work within a week or two, while heavy activities are prohibited for a longer period. Patients who have their hernias repaired with mesh often recover in a number of days. Surgical complications have been estimated to be up to 10%, but most of them can be easily addressed. They include surgical site infections, nerve and blood vessel injuries, injury to nearby organs, and hernia recurrence.

Generally, the use of external devices to maintain reduction of the hernia without repairing the underlying defect (such as hernia trusses, trunks, belts, etc.), is not advised. Exceptions are uncomplicated incisional hernias that arise shortly after the operation (should only be operated after a few months), or inoperable patients.

It is essential that the hernia not be further irritated by carrying out strenuous labour.

What is Cell Cycle Proteins

Sequential activation of members of the cyclin-dependent protein kinase (CDK) family promotes the correct timing and ordering of events required for cell growth and cell division . In addition to driving progress through the cell cycle, CDKs are also the downstream targets of checkpoint pathways. These checkpoints act to ensure that critical cell cycle events have been successfully completed before the cell progresses into the next cell cycle stage. They are composed of a surveillance system that detects when a particular cell cycle event has not been correctly executed and a signal transduction pathway whose ultimate target can be a CDK.
 Monomeric CDKs are inactive and require both association with a positive regulatory subunit, called a cyclin, and phosphorylation on a conserved threonine residue that lies within the activation loop for full activity. Both the CDK and cyclin families have multiple members, but only CDKs 1, 2, 4 and 6, when bound to their cognate cyclins, appear to have major roles in controlling cell cycle progression. These CDK/cyclin complexes are then additionally controlled by mechanisms that include inhibitory phosphorylation, protein association, subcellular localisation and targeted destruction of regulatory proteins.

Major Histocompatibility Complex

Necrosis VS Apoptosis

Extrinsic and Intrinsic pathway for Apoptosis

Overview of the Extrinsic and Intrinsic pathway for Apoptosis

AVM Embolization

Arteriovenous malformations are abnormal clusters of blood vessels which can be seen in any part of the human body. They are congenital in nature. In he brain ,AVM's may have no symptoms at all and the abnormality may be picked during a brain scan for another reason. However, one the commonest presentations is with a bleed in the brain resulting in paralysis or unconsciousness . Another form of presentation can be seizures . Its also known that AVM,s can at time's result in frequent head aches termed "vascular headaches". When detected, AVMs are ideally treated to prevent bleeding in future.




Gleevec

Oxyhemoglobin dissociation curve

The oxygen–haemoglobin dissociation curve (or oxygen–hemoglobin dissociation curve) plots the proportion of haemoglobin in its saturated form on the vertical axis against the prevailing oxygen tension on the horizontal axis. The oxyhaemoglobin dissociation curve is an important tool for understanding how our blood carries and releases oxygen. Specifically, the oxyhaemoglobin dissociation curve relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2), and is determined by what is called "haemoglobin's affinity for oxygen"; that is, how readily haemoglobin acquires and releases oxygen molecules into the fluid that surrounds it.




Bilirubin Metabolism

Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal heme catabolism. Heme is formed from hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile, and its levels are elevated in certain diseases. It is responsible for the yellow color of bruises and the yellow discoloration in jaundice.
Function:
Bilirubin is created by the activity of biliverdin reductase on biliverdin. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin, has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.




Metabolism

Erythrocytes (red blood cells) generated in the bone marrow are disposed of in the spleen when they get old or damaged. This releases hemoglobin, which is broken down to heme, as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the macrophages of the spleen. This unconjugated bilirubin is not soluble in water. It is then bound to albumin and sent to the liver.

In the liver it is conjugated with glucuronic acid, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen, which is further metabolized to stercobilinogen, and finally oxidised to stercobilin. This stercobilin gives feces its brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidized form, urobilin.

Normally, a tiny amount of bilirubin is excreted in the urine, accounting for the light yellow color. If the liver’s function is impaired or when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and appears in the urine, turning it dark amber. The presence of this conjugated bilirubin in the urine can be clinically analyzed, and is reported as an increase in urine bilirubin. However, in disorders involving hemolytic anemia, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. As stated above, the unconjugated bilirubin is not water soluble, and thus one will not see an increase in bilirubin in the urine. Because there is no problem with the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption) and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems.

TCOYD Diabetes-Pregnancy II

Steven Edelman, MD and perinatal specialist Thomas Moore, MD, discuss gestational diabetes including the causes, therapies, and recommendations for keeping mother and baby healthy throughout the pregnancy and delivery.

Mechanism of Capsaicin Pain Relief

The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (VR1). First cloned in 1997, VR1 is an ion channel-type receptor. VR1, which can also be stimulated with heat and physical abrasion, permits cations to pass through the cell membrane and into the cell when activated. The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.
The VR1 ion channel has subsequently been shown to be a member of the superfamily of TRP ion channels, and as such is now referred to as TRPV1. There are a number of different TRP ion channels that have been shown to be sensitive to different ranges of temperature and probably are responsible for our range of temperature sensation. Thus, capsaicin does not actually cause a chemical burn, or indeed any direct tissue damage at all, when chili peppers are the source of exposure. The inflammation resulting from exposure to Capsaicin is believed to be the result of the body's reaction to nerve excitement. For example, the mode of action of capsaicin in inducing bronchoconstriction is thought to involve stimulation of C fibres culminating in the release of neuropeptides. Basically, the body inflames tissues as if it has undergone a burn or abrasion and the resulting inflammation can cause tissue damage in cases of extreme exposure, as is the case for many substances that trick the body into inflaming itself.

Telomere Replication

The ends of linear chromosomes pose unique problems during DNA replication. This video shows how molecular mechanisms solve these problems.

T cell response to MHC II

Tumor Destruction

A Tumor or tumour (via Old French tumour from Latin tumor "swelling")originally meant an abnormal swelling of the flesh. In contemporary English, tumor has evolved to become synonymous with neoplasia , all other forms being called swelling . This tendency has also become common in medical literature. The noun tumefaction, derived from the adjective tumefied, is the current medical term for non-neoplastic tumors .


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Tumors and/or swellings can be caused by:
Other forms of swelling are part of the normal functions of the body and may or may not be included as causes of tumor. Examples include enlargement of the uterus in pregnancy and erection of the penis.


  • Neoplasia, an abnormal proliferation of tissues. Most (not all) neoplasms cause a tumor. Neoplasms (or tumors) may be benign or malignant (cancer).
  • Non-neoplastic causes :
  1. Inflammation, by far the most common cause; tumor is one of the classic signs of inflammation. The lump following a blow on the head is a typical example. Infection is another common cause of inflammation.
  2. Edema, the accumulation of an excessive amount of fluid in the tissues, either with or without inflammation.
  3. Malformation, a congenital anomaly in the architecture of a tissue. A typical example is an epidermal nevus.
  4. Cyst, the accumulation of fluid in a closed structure. Breast cysts are a typical example.
  5. Hemorrhage in a closed structure.

Rheumatoid Arthritis Animation

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder that causes the immune system to attack the joints, causing inflammation (arthritis), and some organs, such as the lungs and skin. It can be a disabling and painful condition, which can lead to substantial loss of functioning mobility due to pain and joint destruction. It is diagnosed with blood tests (especially a test called rheumatoid factor) and X-rays. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in the diseases of joints and connective tissues.

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Various treatments are available. Non-pharmacological treatment includes physical therapy and occupational therapy. Analgesia (painkillers) and anti-inflammatory drugs, as well as steroids, are used to suppress the symptoms, while disease-modifying antirheumatic drugs (DMARDs) are often required to reverse the disease process and prevent long-term damage. Classic DMARDs are methotrexate and sulfasalazine, but also the newer group of biologics which includes highly-effective agents such as infliximab (Remicade), etanercept (Embrel), adalimumab (Humira), abatacept (Orencia) and rituximab (Rituxan/Mabthera).


The name is based on the term "rheumatic fever", an illness which includes joint pain and is derived from the Greek word rheumatos ("flowing"). The suffix -oid ("resembling") gives the translation as joint inflammation that resembles rheumatic fever. The first recognized description of rheumatoid arthritis was made in 1800 by Dr Augustin Jacob Landré-Beauvais (1772-1840) of Paris.

Signs and symptoms

While rheumatoid arthritis primarily affects joints, problems involving all other organs of the body are known to occur. Extra-articular ("outside the joints") manifestations occur in about 15% of individuals with rheumatoid arthritis. It can be difficult to determine whether disease manifestations are directly caused by the rheumatoid process itself, or from side effects of the medications commonly used to treat it - for example, lung fibrosis from methotrexate, or osteoporosis from corticosteroids.

Joints
The arthritis of rheumatoid arthritis is due to synovitis, which is inflammation of the synovial membrane that covers the joint. Joints become red, swollen, tender and warm, and stiffness prevents their use. By definition, RA affects multiple joints (it is a polyarthritis). Most commonly, small joints of the hands, feet and cervical spine are affected, but larger joints like the shoulder and knee can also be involved, differing per individual. Eventually, synovitis leads to erosion of the joint surface, causing deformity and loss of function.

Inflammation in the joints manifests itself as a soft, "doughy" swelling, causing pain and tenderness to palpation and movement, a sensation of localised warmth, and restricted movement. Increased stiffness upon waking is often a prominent feature and may last for more than an hour. These signs help distinguish rheumatoid from non-inflammatory diseases of the joints such as osteoarthritis (sometimes referred to as the "wear-and-tear" of the joints). In RA, the joints are usually affected in a fairly symmetrical fashion although the initial presentation may be asymmetrical.

As the pathology progresses the inflammatory activity leads to erosion and destruction of the joint surface, which impairs their range of movement and leads to deformity. The fingers are typically deviated towards the little finger (ulnar deviation) and can assume unnatural shapes. Common deformities in rheumatoid arthritis are the Boutonniere deformity (Hyperflexion at the proximal interphalangeal joint with hyperextension at the distal interphalangeal joint), swan neck deformity (Hyperextension at the proximal interphalangeal joint, hyperflexion at the distal interphalangeal joint). The thumb may develop a "Z-Thumb" deformity with fixed flexion and subluxation at the metacarpophalangeal joint, and hyperextension at the IP joint.

Skin

The rheumatoid nodule is the cutaneous (strictly speaking subcutaneous) feature most characteristic of rheumatoid arthritis. The initial pathologic process in nodule formation is unknown but is thought to be related to small-vessel inflammation. The mature lesion(a part of an organ or tissue which has been damaged) is defined by an area of central necrosis surrounded by palisading macrophages and fibroblasts and a cuff of cellular connective tissue and chronic inflammatory cells. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the olecranon, the calcaneal tuberosity, the metacarpophalangeal joints, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF titer and severe erosive arthritis. Rarely, they can occur in internal organs.

Several forms of vasculitis are also cutaneous manifestations associated with rheumatoid arthritis. A benign form occurs as microinfarcts around the nailfolds. More severe forms include livedo reticularis, which is a network (reticulum) of erythematous to purplish discoloration of the skin due to the presence of an obliterative cutaneous capillaropathy. (This rash is also otherwise associated with the antiphospholipid-antibody syndrome, a hypercoagulable state linked to antiphospholipid antibodies and characterized by recurrent vascular thrombosis and second trimester miscarriages.)

Other, rather rare, skin associated symtoms include:

* pyoderma gangrenosum, a necrotizing, ulcerative, noninfectious neutrophilic dermatosis.
* Sweet's syndrome, a neutrophilic dermatosis usually associated with myeloproliferative disorders
* drug reactions
* erythema nodosum
* lobular panniculitis
* atrophy of digital skin
* palmar erythema
* diffuse thinning (rice paper skin), and skin fragility (often worsened by corticosteroid use).

DMT biosynthesis

Dimethyltryptamine (DMT), also known as N,N-dimethyltryptamine, is a naturally-occurring tryptamine and potent psychedelic drug,found not only in many plants, but also in trace amounts in the human body where its natural function is undetermined. Structurally, it is analogous to the neurotransmitter serotonin and other psychedelic tryptamines such as 5-MeO-DMT and 4-HO-DMT. DMT is created in small amounts by the human body during normal metabolism by the enzyme tryptamine-N-methyltransferase. Many cultures, indigenous and modern, ingest DMT as a psychedelic in extracted or synthesized forms. Pure DMT at room temperature is a clear or white to yellowish-red crystalline solid. A laboratory synthesis of DMT was first reported in 1931, and it was later found in many plants





Dimethyltryptamine. (2009, June 16). In Wikipedia, The Free Encyclopedia. Retrieved 03:23, June 16, 2009, from http://en.wikipedia.org/w/index.php?title=Dimethyltryptamine&oldid=296681896

Tryptophan Operon


Trp operon is an operon in bacteria which promotes the production of tryptophan when tryptophan isn't present in the environment. Discovered in 1953 by Jacques Monod and colleagues, the trp operon in E. coli was the first repressible operon to be discovered. While the lac operon can be activated by a chemical (allolactose), the tryptophan (Trp) operon is inhibited by a chemical (tryptophan). This operon contains five structural genes: trp E, trp D, trp C, trp B, and trp A, which encodes tryptophan synthetase. It also contains a promoter which binds to RNA polymerase and an operator which blocks transcription when bound to the protein synthesized by the repressor gene (trp R) that binds to the operator. In the lac operon, lactose binds to the repressor protein and prevents it from repressing gene transcription, while in the trp operon, tryptophan binds to the repressor protein and enables it to repress gene transcription. Also unlike the lac operon, the trp operon contains a leader peptide and an attenuator sequence which allows for graded regulation.

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It is an example of negative regulation of gene expression. Within the operon's regulatory sequence, the operator is blocked by the repressor protein in the presence of tryptophan (thereby preventing transcription) and is liberated in tryptophan's absence (thereby allowing transcription). The process of attenuation complements this regulatory action. Repression The repressor for the trp operon is produced upstream by the trpR gene, which is continually expressed. It creates monomers, which associate into tetramers. When tryptophan is present, it binds to the tryptophan repressor tetramers, and causes a change in conformation, which allows the repressor to bind the operator, which prevents RNA polymerase from binding or transcribing the operon, so tryptophan is not produced. When tryptophan is not present, the repressor cannot bind the operator, so transcription can occur. This is therefore a negative feedback mechanism.

Attenuation Because repression of this operon is still "leaky," another system of controlling expression is also needed: Attenuation. At the beginning of the transcribed genes of the trp operon is a leader sequence, which codes for a very short polypeptide. Near the end of this sequence, two tryptophans are coded for next to each other. Because tryptophan is a fairly uncommon amino acid, this is highly unusual. Since in prokaryotes the ribosomes begin translating the mRNA as soon as the RNA polymerase has moved farther down the DNA sequence, upstream translation occurs simultaneously with transcription of downstream genes. So, as soon as the polymerase has created the mRNA for the leader sequence, it is being translated. When the ribosome reaches the double-trp codons, if enough trp is present, the ribosome will not be delayed, and will continue translating until it reaches the stop codon and falls off the leader transcript. A hairpin will then form in the mRNA transcript (remember, still attached to RNA polymerase on other end) between regions 1-2, and 3-4, which destabilizes the RNA polymerase and halts transcription of the rest of the operon, thus preventing production of trp. On the other hand, if there is little or no trp available, the ribosome will be delayed or stopped on the double-trp, and a hairpin will form between regions 2-3 of the mRNA instead. This does not destabilize the polymerase, so transcription and translation occur. Similar mechanism regulates the synthesis of histidine, phenylalanine and threonine.