Supraclavicular lymph nodes

Regional lymph nodes

Front view of neck.

Anterolateral view of head and neck.

Deep Lymph Nodes
1. Submental
2. Submandibular (Submaxillary)

Anterior Cervical Lymph Nodes (Deep)
3. Prelaryngeal
4. Thyroid
5. Pretracheal
6. Paratracheal

Deep Cervical Lymph Nodes
7. Lateral jugular
8. Anterior jugular
9. Jugulodigastric

Inferior Deep Cervical Lymph Nodes
10. Juguloomohyoid
11. Supraclavicular (scalene)

Supraclavicular lymph nodes are lymph nodes found superior to the clavicle, palpable in the supraclavicular fossa.
The most notable supraclavicular lymph node is Virchow's node. 

Right supraclavicular lymph node

• Location: Located on the right side in the hollow above the clavicle, just lateral to where it joins the sternum.
• Lymphatic drainage: Mediastinum, lungs, esophagus
• Common causes of enlargement: Lung, retroperitoneal or gastrointestinal cancer

Left supraclavicular lymph node

• Location: Located on the left side in the hollow above the clavicle, just lateral to where it joins the sternum.
• Lymphatic drainage: Thorax, abdomen via thoracic duct.
• Common causes of enlargement: Lymphoma, thoracic or retroperitoneal cancer, bacterial or fungal infection.

Regional lymph tissue. (Supraclavicular near top, in green.)⋅               

 

 

Integrated Management of Childhood Illness (IMCI)

Rajat Das Gupta

Every day, millions of parents seek health care for their sick children, taking them to hospitals, health centres, pharmacists, doctors and traditional healers. Surveys reveal that many sick children are not properly assessed and treated by these health care providers, and that their parents are poorly advised. At first-level health facilities in low-income countries, diagnostic supports such as radiology and laboratory services are minimal or non-existent, and drugs and equipment are often scarce. Limited supplies and equipment, combined with an irregular flow of patients, leave doctors at this level with few opportunities to practice complicated clinical procedures. Instead, they often rely on history and signs and symptoms to determine a course of management that makes the best use of the available resources

These factors make providing quality care to sick children a serious challenge. WHO and UNICEF have addressed this challenge by developing a strategy called the Integrated Management of Childhood Illness (IMCI).
 

What is IMCI?

IMCI is an integrated approach to child health that focuses on the well-being of the whole child. IMCI aims to reduce death, illness and disability, and to promote improved growth and development among children under five years of age. IMCI includes both preventive and curative elements that are implemented by families and communities as well as by health facilities.
The strategy includes three main components:

• Improving case management skills of health-care staff
• Improving overall health systems
• Improving family and community health practices.

In health facilities, the IMCI strategy promotes the accurate identification of childhood illnesses in outpatient settings, ensures appropriate combined treatment of all major illnesses, strengthens the counselling of caretakers, and speeds up the referral of severely ill children. In the home setting, it promotes appropriate care seeking behaviours, improved nutrition and preventative care, and the correct implementation of prescribed care.

Why is IMCI better than single-condition approaches?

Children brought for medical treatment in the developing world are often suffering from more than one condition, making a single diagnosis impossible. IMCI is an integrated strategy, which takes into account the variety of factors that put children at serious risk. It ensures the combined treatment of the major childhood illnesses, emphasizing prevention of disease through immunization and improved nutrition.

How is IMCI implemented?

Introducing and implementing the IMCI strategy in a country is a phased process that requires a great deal of coordination among existing health programmes and services. It involves working closely with local governments and ministries of health to plan and adapt the principles of the approach to local circumstances. The main steps are:

• Adopting an integrated approach to child health and development in the national health policy.
• Adapting the standard IMCI clinical guidelines to the country’s needs, available drugs, policies, and to the local foods and language used by the population.
• Upgrading care in local clinics by training health workers in new methods to examine and treat children, and to effectively counsel parents.
• Making upgraded care possible by ensuring that enough of the right low-cost medicines and simple equipment are available.
• Strengthening care in hospitals for those children too sick to be treated in an outpatient clinic.
• Developing support mechanisms within communities for preventing disease, for helping families to care for sick children, and for getting children to clinics or hospitals when needed.

IMCI has already been introduced in more than 75 countries around the world.

What has been done to evaluate the IMCI strategy?

CAH has undertaken a Multi-Country Evaluation (MCE) to evaluate the impact, cost and effectiveness of the IMCI strategy. The results of the MCE support planning and advocacy for child health interventions by ministries of health in developing countries, and by national and international partners in development. To date, MCE has been conducted in Brazil, Bangladesh, Peru, Uganda and the United Republic of Tanzania.
The results of the MCE indicate that:

• IMCI improves health worker performance and their quality of care;
• IMCI can reduce under-five mortality and improve nutritional status, if implemented well;
• IMCI is worth the investment, as it costs up to six times less per child correctly managed than current care;
• child survival programmes require more attention to activities that improve family and community behaviour;
• the implementation of child survival interventions needs to be complemented by activities that strengthen system support;
• a significant reduction in under-five mortality will not be attained unless large-scale intervention coverage is achieved.

Transplant rejection

Rajat Das Gupta

Transplant rejection is when a transplant recipient's immune system attacks a transplanted organ or tissue. See also graft-versus-host disease.

Causes, incidence, and risk factors

Your body's immune system protects you from potentially harmful substances, such as microorganisms, toxins, and cancer cells. These harmful substances have proteins called antigens on their surfaces. If your immune system identifies antigens that are foreign (not part of your body), it will attack them.
In the same way, foreign blood or tissue can trigger a blood transfusion reaction or transplant rejection. To help prevent this, tissue is "typed" before the transplant procedure to identify the antigens it contains.
Though tissue typing ensures that the organ or tissue is as similar as possible to the tissues of the recipient, the match is usually not perfect. No two people (except identical twins) have identical tissue antigens.
Immunosuppressive drugs are needed to prevent organ rejection. Otherwise, organ and tissue transplantation would almost always cause an immune response and result in destruction of the foreign tissue.
There are some exceptions, however. Corneal transplants are rarely rejected because corneas have no blood supply -- immune cells and antibodies do not reach the cornea to cause rejection. In addition, transplants from one identical twin to another are almost never rejected.

Symptoms

• The organ does not function properly
• General discomfort, uneasiness, or ill feeling
• Pain or swelling in the location of the organ (rare)
• Fever (rare)

The symptoms vary depending on the transplanted organ or tissue. For example, patients who reject a kidney may have less urine, and patients who reject a heart may have symptoms of heart failure.

Signs and tests

The doctor will feel the area over and around the transplanted organ, which may feel tender to you (particularly with transplanted kidneys).
There are often signs that the organ isn't functioning properly. For example:

• Less urine output with kidney transplants
• Shortness of breath and less tolerance to exertion with heart transplants
• Yellow skin color and easy bleeding with liver transplants

A biopsy of the transplanted organ can confirm that it is being rejected. A routine biopsy is often performed to detect rejection early, before symptoms develop.
When organ rejection is suspected, one or more of the following tests may be performed prior to organ biopsy:

• Abdominal CT scan
• Chest x-ray
• Heart echocardiography
• Kidney arteriography
• Kidney ultrasound
• Lab tests of kidney or liver function

Treatment

The goal of treatment is to make sure the transplanted organ or tissue functions properly, while at the same time suppressing the recipient's immune response. Suppressing the immune response can treat and prevent transplant rejection.
Many different drugs can be used to suppress the immune response. The dosage of the medication depends on the patient's status. The dose may be very high while the tissue is actually being rejected, and then reduced to a lower level to prevent it from happening again.

Expectations (prognosis)

Some organs and tissues are more successfully transplanted than others. If rejection begins, immunosuppressive drugs may stop the rejection. Then, you must take immunosuppressive drugs for the rest of your life.
However, immunosuppressive treatment is not always successful.

Complications

• Infections (because the person's immune system is constantly suppressed)
• Loss of function of the transplanted organ/tissue
• Side effects of medications, which may be severe

Calling your health care provider

Call your health care provider if the transplanted organ or tissue does not seem to be working properly or if other symptoms occur. Also, call your health care provider if medication side effects develop.

Prevention

ABO blood typing and HLA (tissue antigen) typing before transplantation helps to ensure a close match. Suppressing the immune system is usually necessary for the rest of the transplant recipient's life to prevent the tissue from being rejected. Being careful to take post-transplant medications properly, and being closely monitored by your doctor may help prevent rejection.

Aprotinin

Rajat Das Gupta The drug aprotinin (Trasylol, Bayer), is the bovine version of the small protein basic pancreatic trypsin inhibitor, or BPTI, which inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use was to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death;[1] this was confirmed by follow-up studies. Trasylol was entirely and permanently withdrawn in May 2008, except for very restricted research use.Aprotinin is a monomeric (single-chain) globular polypeptide derived from bovine lung tissue. It has a molecular weight of 6512 and consists of 16 different amino acid types arranged in a chain 58 residues long[2][3] that folds into a stable, compact tertiary structure of the 'small SS-rich" type, containing 3 disulfides, a twisted β-hairpin and a C-terminal α-helix.[4] The amino acid sequence for bovine BPTI is RPDFC LEPPY TGPCK ARIIR YFYNA KAGLC QTFVY GGCRA KRNNF KSAED CMRTC GGA.[5] There are 10 positively-charged lysine (K) and arginine (R) side chains and only 4 negative aspartate (D) and glutamates (E), making the protein strongly basic, which accounts for the basic in its name. (Because of the usual source organism, BPTI is sometimes referred to as bovine pancreatic trypsin inhibitor.) The high stability of the molecule is due to the 3 disulfide bonds linking the 6 cysteine members of the chain (Cys5-Cys55, Cys14-Cys38 and Cys30-Cys51).[6] The long, basic lysine 15 side chain on the exposed loop (at top left in the image) binds very tightly in the specificity pocket at the active site of trypsin and inhibits its enzymatic action. BPTI is synthesized as a longer, precursor sequence, which folds up and then is cleaved into the mature sequence given above. BPTI is the classic member of the protein family of Kunitz-type serine protease inhibitors. Its physiological functions include the protective inhibition of the major digestive enzyme trypsin when small amounts are produced by cleavage of the trypsinogen precursor during storage in the pancreas. Mechanism of drug action Aprotinin inhibits several serine proteases, specifically trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/ml, and kallikrein at 300,000 IU/ml.[3] Its action on kallikrein leads to the inhibition of the formation of factor XIIa. As a result, both the intrinsic pathway of coagulation and fibrinolysis are inhibited. Its action on plasmin independently slows fibrinolysis.[2] Drug efficacy In cardiac surgery with a high risk of significant blood loss, aprotinin significantly reduced bleeding, mortality and hospital stay.[3] Beneficial effects were also reported in high-risk orthopedic surgery.[3] In liver transplantation, initial reports of benefit were overshadowed by concerns about toxicity.[7] In a meta-analysis performed in 2004, transfusion requirements decreased by 39% in coronary artery bypass graft (CABG) surgery.[8] In orthopedic surgery, a decrease of blood transfusions was likewise confirmed.[9] Drug safety There have been concerns about the safety of aprotinin.[3] Anaphylaxis (a severe allergic reaction) occurs at a rate of 1:200 in first-time use, but serology (measuring antibodies against aprotinin in the blood) is not carried out in practice to predict anaphylaxis risk because the correct interpretation of these tests is difficult.[3] Thrombosis, presumably from overactive inhibition of the fibrinolytic system, may occur at a higher rate, but until 2006 there was limited evidence for this association.[3][8] Similarly, while biochemical measures of renal function were known to occasionally deteriorate, there was no evidence that this greatly influenced outcomes.[3] A study performed in cardiac surgery patients reported in 2006 showed that there was indeed a risk of acute renal failure, myocardial infarction and heart failure, as well as stroke and encephalopathy.[10] The study authors recommend older antifibrinolytics (such as tranexamic acid) in which these risks were not documented.[10] The same group updated their data in 2007 and demonstrated similar findings.[11] In September 2006, Bayer A.G. was faulted by the FDA for not revealing during testimony the existence of a commissioned retrospective study of 67,000 patients, 30,000 of whom received aprotinin and the rest other anti-fibrinolytics. The study concluded aprotinin carried greater risks. The FDA was alerted to the study by one of the researchers involved. Although the FDA issued a statement of concern they did not change their recommendation that the drug may benefit certain subpopulations of patients.[12] In a Public Health Advisory Update dated October 3, 2006, the FDA recommended that "physicians consider limiting Trasylol use to those situations in which the clinical benefit of reduced blood loss is necessary to medical management and outweighs the potential risks" and carefully monitor patients.[13] On October 25, 2007, the FDA issued a statement regarding the "Blood conservation using antifibrinolytics" (BART) randomized trial in a cardiac surgery population. The preliminary findings suggest that, compared to other antifibrinolytic drugs (epsilon-aminocaproic acid and tranexamic acid) aprotinin may increase the risk of death.[14] On October 29, 2006 the Food and Drug Administration issued a warning that aprotinin may have serious kidney and cardiovascular toxicity. The producer, Bayer, reported to the FDA that additional observation studies showed that it may increase the chance for death, serious kidney damage, congestive heart failure and strokes. FDA warned clinicians to consider limiting use to those situations where the clinical benefit of reduced blood loss is essential to medical management and outweighs the potential risks.[15] On November 5, 2007, Bayer announced that it was withdrawing Aprotinin because of a Canadian study that showed it increased the risk of death when used to prevent bleeding during heart surgery.[16] Two studies published in early 2008, both comparing aprotinin with aminocaproic acid, found that mortality was increased by 32[17] and 64%,[18] respectively. One study found an increased risk in need for dialysis and revascularisation.[18] No cases of bovine spongiform encephalopathy transmission by aprotinin have been reported, although the drug was withdrawn in Italy due to fears of this.[3] In vitro use Small amounts of aprotinin can be added to tubes of drawn blood to enable laboratory measurement of certain rapidly degraded proteins such as glucagon. In cell biology aprotinin is used as an enzyme inhibitor to prevent protein degradation during lysis or homogenization of cells and tissues. Aprotinin can be labelled with fluorescein isothiocyanate. The conjugate retains its antiproteolytic and carbohydrate-binding properties[19] and has been used as a fluorescent histochemical reagent for staining glycoconjugates (mucosubstances) that are rich in uronic or sialic acids.[20] History Initially named "kallikrein inactivator", aprotinin was first isolated from cow parotid glands in 1930.[21] and independently as a trypsin inhibitor from bovine pancreas in 1936.[22] It was purified from bovine lung in 1964.[23] As it inhibits pancreatic enzymes, it was initially used in the treatment for acute pancreatitis, in which destruction of the gland by its own enzymes is thought to be part of the pathogenesis.[24] Its use in major surgery commenced in the 1960s.[25] BPTI is one of the most thoroughly studied proteins in terms of structural biology, experimental and computational dynamics, mutagenesis, and folding pathway. It was one of the earliest protein crystal structures solved, in 1970 in the laboratory of Robert Huber,[26] and was the first protein to have its structure determined by NMR spectroscopy, in the laboratory of Kurt Wuthrich at the ETH in Zurich in the early 1980s.[27][28] Because it is a small, stable protein whose structure had been determined at high resolution by 1975,[29] it was the first macromolecule of scientific interest to be simulated using molecular dynamics computation, in 1977 by J. Andrew McCammon and Bruce Gelin, in the Karplus group at Harvard.[30] That study confirmed the then-surprising fact found in the NMR work[31] that even well-packed aromatic sidechains in the interior of a stable protein can flip over rather rapidly (microsecond to millisecond time scale). Rate constants were determined by NMR for the hydrogen exchange of individual peptide NH groups along the chain, ranging from too fast to measure on the most exposed surface to many months for the most buried hydrogen-bonded groups in the center of the β sheet, and those values also correlate fairly well with degree of motion seen in the dyamics simulations. BPTI was important in the development of knowledge about the process of protein folding, the self-assembly of a polypeptide chain into a specific arrangement in 3D. The problem of achieving the correct pairings among the 6 Cys sidechains was shown to be especially difficult for the two buried, close-together SS near the BPTI chain termini, requiring a non-native intermediate for folding the mature sequence in vitro (it was later discovered that the precursor sequence folds more easily in vivo). BPTI was the cover image on a protein folding compendium volume by Thomas Creighton in 1992.[32] References ^ Trasylol.com (2007-11-05). "Bayer Temporarily Suspends Global Trasylol Marketing" (PDF). Press release. http://www.trasylol.com/Trasylol_11_05_07.pdf. Retrieved 2007-12-03.  ^ a b Mannucci PM; Mannucci, Pier Mannuccio (1998). "Hemostatic drugs". N. Engl. J. Med. 339 (4): 245–53. doi:10.1056/NEJM199807233390407. PMID 9673304.  ^ a b c d e f g h i Mahdy AM, Webster NR (2004). "Perioperative systemic haemostatic agents". British journal of anaesthesia 93 (6): 842–58. doi:10.1093/bja/aeh227. PMID 15277296.  ^ Richardson, J.S. (1981). "Anatomy and Taxonomy of Protein Structure". Advances in Protein Chemistry 34: 167–339. doi:10.1016/S0065-3233(08)60520-3. PMID 7020376.  ^ Kassell B, Radicevic M, Ansfield MJ, Laskowski M (1965). "The basic trypsin inhibitor of bovine pancreas. IV. The linear sequence of the 58 amino acids". Biochem. Biophys. Res. Commun. 18: 255–8. doi:10.1016/0006-291X(65)90749-7. PMID 14282026.  ^ Kassell B, Laskowski M (1965). "The basic trypsin inhibitor of bovine pancreas. V. The disulfide linkages". Biochem. Biophys. Res. Commun. 20 (4): 463–8. doi:10.1016/0006-291X(65)90601-7. PMID 5860161.  ^ Xia VW, Steadman RH (2005). "Antifibrinolytics in orthotopic liver transplantation: current status and controversies". Liver Transpl. 11 (1): 10–8. doi:10.1002/lt.20275. PMID 15690531.  ^ a b Sedrakyan A, Treasure T, Elefteriades JA (2004). "Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials". J. Thorac. Cardiovasc. Surg. 128 (3): 442–8. doi:10.1016/j.jtcvs.2004.03.041. PMID 15354106.  ^ Shiga T, Wajima Z, Inoue T, Sakamoto A (2005). "Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials". Anesth. Analg. 101 (6): 1602–7. doi:10.1213/01.ANE.0000180767.50529.45. PMID 16301226.  ^ a b Mangano DT, Tudor IC, Dietzel C (2006). "The risk associated with aprotinin in cardiac surgery". N. Engl. J. Med. 354 (4): 353–65. doi:10.1056/NEJMoa051379. PMID 16436767.  ^ Mangano D, Miao Y, Vuylsteke A, Tudor I, Juneja R, Filipescu D, Hoeft A, Fontes M, Hillel Z, Ott E, Titov T, Dietzel C, Levin J (2007). "Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery". JAMA 297 (5): 471–9. doi:10.1001/jama.297.5.471. PMID 17284697.  ^ Gardiner Harris (2006-09-30). "F.D.A. Says Bayer Failed to Reveal Drug Risk Study - New York Times". The New York Times. http://www.nytimes.com/2006/09/30/health/30fda.html. Retrieved 2007-11-05.  ^ "Facts & Comparisons: Trasylol Public Health Advisory Update". http://factsandcomparisons.com/News/ArticlePage.aspx?id=7387. Retrieved 2007-11-05.  ^ U.S. Food and Drug Administration. "Early Communication about an Ongoing Safety Review Aprotinin Injection (marketed as Trasylol)". Archived from the original on 2007-10-30. http://web.archive.org/web/20071030053834/http://www.fda.gov/cder/drug/early_comm/aprotinin.htm. Retrieved 2007-10-28.  ^ U.S. Food and Drug Administration. "Information for Healthcare Professionals; Aprotinin (marketed as Trasylol)". Archived from the original on 2006-10-10. http://web.archive.org/web/20061010033920/http://www.fda.gov/cder/drug/InfoSheets/HCP/aprotininHCP.htm. Retrieved 2006-10-30.  ^ Gardiner Harris (2007-11-05). "Bayer Withdraws Heart Surgery Drug". The New York Times. http://www.nytimes.com/2007/11/05/health/05cnd-bayer.html?hp. Retrieved 2007-11-05.  ^ Shaw AD, Stafford-Smith M, White WD, et al. (2008). "N Engl J Med". New England Journal of Medicine 358 (8): 784–793. doi:10.1056/NEJMoa0707768. PMID 18287601. http://content.nejm.org/cgi/content/abstract/358/8/784.  ^ a b Schneewiss S, Seeger JD, Landon J, Walker AM (2008). "Aprotinin during coronary-artery bypass grafting and risk of death". N Engl J Med 358 (8): 771–783. doi:10.1056/NEJMoa0707571. PMID 18287600. http://content.nejm.org/cgi/content/abstract/358/8/771.  ^ Stoddart RW, Kiernan,JA (1973). "Aprotinin, a carbohydrate-binding protein". Histochemie 34: 275–280. doi:10.1007/BF00306299. http://www.springerlink.com/content/uj80u51557v31316/?p=e12159ae3aba4710b31693618d9187fa&pi=0.  ^ Kiernan JA, Stoddart RW (1973). "Fluorescent-labelled aprotinin: a new reagent for the histochemical detection of acid mucosubstances". Histochemie 34: 77–84. http://www.springerlink.com/content/n027274324786045/?p=2d84250aa96a47a49bff1a91b8f608bc&pi=5.  ^ Kraut H, Frey EK, Bauer E (1930). "Über die Inaktivierung des kallikreins" (in German). Hoppe-Seyler's Z Physiol Chem 192: 1–21. doi:10.1515/bchm2.1930.192.1-3.1.  ^ Kunitz M, Northrup J (1936). "Isolation from beef pancreas of crystalline trypsinogen, trypsin, trypsin inhibitor, and an inhibitor trypsin compound". J Gen Physiol 19: 991–1007. doi:10.1085/jgp.19.6.991. http://www.jgp.org/cgi/reprint/19/6/991.  ^ Kraut H, Bhargava N (1964). "Versuche zur Isolierung des Kallikrein-Inaktivators aus Rinderlunge and seine Identifizierung mit dem Inaktivator aus Rinderparotis" (in German). Hoppe-Seyler's Z. Physiol. Chem. 338: 231–7. PMID 14330402.  ^ Nugent FW, Warren KW, Jonasson H, Garciadeparedes G (1964). "Early experience with trasylol in the treatment of acute pancreatitis". South. Med. J. 57: 1317–21. PMID 14195953.  ^ Tice DA, Worth Jr MH, Clauss RH, Reed GH (1964). "The inhibition of trasylol of fibrinolytic activity associated with cardiovascular operations". Surgery, gynecology & obstetrics 119: 71–4. PMID 14179354.  ^ Huber, R., et al. (1970). "The Basic Trypsin Inhibitor of Bovine Pancreas. I. Structure Analysis and Conformation of the Polypeptide Chain". Naturwissenschaften 57 (8): 389–92. PMID 5447861.  ^ Wagner, G. and Wuthrich, K. (1982). "Sequential resonance assignments in protein 1H nuclear magnetic resonance spectra: basic pancreatic trypsin inhibitor". Journal of Molecular Biology 155 (3): 347–366. doi:10.1016/0022-2836(82)90009-2. PMID 6176717.  ^ Havel, T.F. and Wuthrich, K. (1985). "An evaluation of the combined use of nuclear magnetic resonance and distance geometry for the determination of protein conformations in solution". Journal of Molecular Biology 182 (2): 281–294. doi:10.1016/0022-2836(85)90346-8. PMID 2582141.  ^ Deisenhofer, J. and Steigemann, W. (1975). "Crystallographic Refinement of the Structure of Bovine Pancreatic Trypsin Inhibitor at 1.5 Angstroms Resolution". Acta Crystallographica B 31: 238. doi:10.1107/S0567740875002415.  ^ McCammon JA, Gelin BR, Karplus M (1977). "Dynamics of folded proteins". Nature 267 (5612): 585–90. doi:10.1038/267585a0. PMID 301613.  ^ Wuthrich, K. and Wagner, G. (1975). "NMR investigations of the dynamics of the aromatic amino acid residues in the basic pancreatic trypsin inhibitor". FEBS Letters 50 (2): 265–268. doi:10.1016/0014-5793(75)80504-7. PMID 234403.  ^ Thomas E. Creighton (1992). Protein Folding. W. H. Freeman. ISBN 978-0716770275.

                      Pancreatic trypsin inhibitor

						BPTI sequence, with its folded 3D structure represented by a ribbon for the secondary structure and a stick model (gray) for the backbone and sidechains.
Identifiers
Organism	Bos taurus (domestic cow)
Symbol	PTI
Entrez	404172
RefSeq (mRNA)	NM_001001554
RefSeq (Prot)	NP_001001554
UniProt	P00974
Other data
Chromosome	13: 75.02 - 75.03 Mb

Systematic (IUPAC) name
Aprotinin
Identifiers
CAS number	9087-70-1 9004-04-0
ATC code	B02AB01
KEGG	D02971
Synonyms	Trasylol, bovine pancreatic trypsin inhibitor
Chemical data
Formula	C284H432N84O79S7
Mol. mass	6511.51 g/mol
Pharmacokinetic data
Bioavailability	100% (intravenous)
Therapeutic considerations
Pregnancy cat.	X
Legal status	RX/POM
Dependence liability	None
Routes	Intravenous

Ticlopidine

 Rajat Das Gupta

 
 WARNING: Rarely, this medication has caused serious, sometimes life-threatening blood and immune disorders (agranulocytosis, aplastic anemia, neutropenia, thrombotic thrombocytopenic purpura-TTP). Symptoms may appear within the first few days after starting this medication. Seek immediate attention if you notice any of these rare but serious side effects: difficulty speaking, weakness on one side of the body, seizures, red pinpoint-sized bleeding spots on the skin, dark-colored urine, or yellowing of eyes/skin (see also Side Effects section).
Your doctor will be monitoring your blood counts before and regularly during treatment, especially the first 3 months of therapy. It is important that you keep all your medical and laboratory appointments.
USES: This medication is used to prevent strokes in people who cannot take aspirin or for whom aspirin has failed to work. It may also be used in combination with aspirin following certain types of heart procedures (e.g., coronary stent implant).Ticlopidine is an anti-platelet drug. It works by making your blood less likely to clot.
HOW TO USE: Read the Patient Information Leaflet available from your pharmacist. Consult your doctor or pharmacist if you have any questions.Take this medication with food or just after a meal, usually twice daily, or as directed by your doctor. Do not take this medication two hours before or after taking antacids.Duration of therapy is based on your medical condition. If you are taking this medication to prevent clots after a stent implant, it is generally taken with aspirin for up to 30 days unless otherwise directed by your doctor. Consult your doctor for more details.Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day. Do not increase your dose or take this more often than prescribed. It is important to continue taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor.
SIDE EFFECTS: See also the Warning section.Diarrhea, stomach upset/pain, nausea, vomiting, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor immediately if any of these unlikely but serious side effects occur: severe/persistent or bloody diarrhea, vomit that looks like coffee grounds, blood in the urine, bleeding from gums or nose, persistent dizziness.Tell your doctor immediately if any of these rare but very serious side effects occur: signs of new infection (e.g., chills, persistent sore throat), unusual weakness/fatigue, easy bruising or bleeding, mental/mood changes, numbness/tingling of arms/legs, persistent nausea/vomiting, severe stomach/abdominal pain, change in the amount of urine.A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: history of blood or immune disorders (thrombotic thrombocytopenic purpura, aplastic anemia, agranulocytosis, neutropenia), serious/active bleeding (e.g., bleeding stomach ulcers), severe liver disease.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver or kidney problems, bleeding/blood clotting disorders, conditions that put you at risk of bleeding (e.g., stomach ulcers), high cholesterol or triglyceride levels.This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.Before having surgery, tell your doctor or dentist that you are taking this medication.While you are taking this medication, it may take longer than usual for bleeding to stop if you have a cut or injury. Use caution with sharp objects like safety razors or nail cutters and avoid activities such as contact sports to lower the chance of getting cut, bruised, or injured.Caution is advised when using this drug in the elderly because they may be more sensitive to the side effects of the drug.This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.It is not known whether this drug passes into breast milk. Breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.DRUG INTERACTIONS: See also the How To Use section.Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.This drug should not be used with the following medication because very serious interactions may occur: mifepristone.If you are currently using the medication listed above, tell your doctor or pharmacist before starting ticlopidine.Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other antiplatelet drugs (e.g., cilostazol, clopidogrel), cimetidine, digoxin, phenytoin, theophylline, tipranavir, tizanidine.Other drugs like this medication that affect blood clotting may increase your risk of bleeding. Examples are "blood thinners" (anticoagulants such as enoxaparin, heparin, warfarin). Follow your doctor's instructions carefully and continue your medications as directed. Tell your doctor immediately if you notice unusual bleeding. Consult your doctor or pharmacist for more details.For certain conditions, you may be instructed by your doctor to take ticlopidine together with aspirin. Follow your doctor's instructions and continue aspirin as directed. If you are not currently taking aspirin, consult your doctor before starting it for any medical condition. Check the labels on all your medicines because they may contain aspirin or aspirin-like NSAIDs (e.g., ibuprofen, naproxen) that can increase the risk of bleeding. Ask your pharmacist about the safe use of those products.This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.
NOTES: See also the Warning section.Do not share this medication with others.Laboratory and/or medical tests (e.g., complete blood counts, platelet counts, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.
STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.