Վիքիպեդիա

Մասնակից:Տաթև Հարությունյան/Ավազարկղ

Ծանրության աստիճանի գնահատում

խմբագրել

Սուր պանկրեատիտով հիվանդների մի մասն առողջանում է։ Որոշների մոտ կարող է առաջանալ աբսցես, պսևդոցիստ կամ դուոդենալ անանցանելիություն։ 5% դեպքերում կարող է առաջանալ ՍՇԴՀ, ԴՆՄ։ Առանձնացնում են թեթև և ծանր աստիճանի սուր պանկրեատիտ։

Սուր պանկրեատիտի դեպքում նեկրոզային օջախների քանակը որոշում է հետագա կլինիկական ընթացքը։ Սուր պանկրեատիտի դեպքերի 20%–ը սուր են և մահացությունը կազմում է 20%։ Ծանր աստիճանի սուր պանկրեատիտի դեպքում անհրաժեշտ է բժշկական անհապաղ միջամտություն։

Նեկրոզին հաջորդում է համակարգային բորբոքային պատասխանի համախտանիշը (ՀԲՊՀ), որը

Necrosis will be followed by a systemic inflammatory response syndrome (SIRS) and will determine the immediate clinical course. The further clinical course is then determined by bacterial infection. SIRS is the cause of bacterial (Gram negative) translocation from the patients colon.

There are several ways to help distinguish between these two forms. One is the above-mentioned Ranson Score.

In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most,[1][2] but not all[3] studies report that the Apache score may be more accurate. In the negative study of the APACHE-II,[3] the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at www.sfar.org.

Practice guidelines state:

2006: "The two tests that are most helpful at admission in distinguishing mild from severe acute pancreatitis are APACHE-II score and serum hematocrit. It is recommended that APACHE-II scores be generated during the first 3 days of hospitalization and thereafter as needed to help in this distinction. It is also recommended that serum hematocrit be obtained at admission, 12 h after admission, and 24 h after admission to help gauge adequacy of fluid resuscitation."[4]
2005: "Immediate assessment should include clinical evaluation, particularly of any cardiovascular, respiratory, and renal compromise, body mass index, chest x ray, and APACHE II score"[5]

Ռենսոնի սանդղակ

խմբագրել

Ռենսոնի սանդղակն օգտագործվում է սուր պանկրեատիտի ծանրության աստիճանը գնահատելու համար։ Ներկայացվել է 1974թ–ին։

Ընդունման պահին

խմբագրել
  • տարիքը > 55
  • լեյոկցիտները > 16000 բջիջ/մմ3
  • արյան գլյուկոզը > 11.1 մմոլ/լ (> 200 մգ/դլ)
  • շիճուկային ԱՍՏ > 250 միջ․միավ․/լ
  • շիճուկային ԼԴՀ > 350 միջ․միավ․/լ

48 ժամ անց

խմբագրել
  • Կալցիում (շիճուկային կալցիում < 2.0 մմոլ/լ (< 8.0 մգ/դլ)
  • Հեմատոկրիտի նվազում >10%
  • Սատուրացիա (PO2 < 60 մմ սս)
  • Արյան մեջ միջանյութի քանակի ավելացում մինչև 1.8մմոլ/լ (5մգ/դլ) ներերակային հիդրատացիայից հետո
  • Հիմքի դեֆիցիտ > 4 մգ էկվ/լ

The criteria for point assignment is that a certain breakpoint be met at any time during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis.

Alternatively, pancreatitis can be diagnosed by meeting any of the following:[2]

Alternative Ranson score

խմբագրել

Ranson's score of ≥ 8 Organ failure Substantial pancreatic necrosis (at least 30% glandular necrosis according to contrast-enhanced CT)

Interpretation If the score ≥ 3, severe pancreatitis likely. If the score < 3, severe pancreatitis is unlikely Or

Score 0 to 2 : 2% mortality Score 3 to 4 : 15% mortality Score 5 to 6 : 40% mortality Score 7 to 8 : 100% mortality

APACHE II սանդղակ

խմբագրել

"Acute Physiology And Chronic Health Evaluation" (APACHE II, սուր ֆի) score > 8 points predicts 11% to 18% mortality[4]

  • Hemorrhagic peritoneal fluid
  • Ճարպակալում
  • Indicators of organ failure
  • հիպոտենզիա (SBP <90 mmHG) կամ տախիկարդիա > 130 զարկ/րոպե
  • PO2 <60 մմ սս
  • Oliguria (<50 mL/h) or increasing BUN and creatinine
  • Շիճուկային կալցիում < 1.90 մմոլ/լ (<8.0 մգ/դլ) կամ շիճուկային ալբումին <33 գ/լ (<3.2գճ/դլ)

Բալթազարի սանդղակ

խմբագրել

Developed in the early 1990s by Emil J. Balthazar et al.,[6] the Computed Tomography Severity Index (CTSI) is a grading system used to determine the severity of acute pancreatitis. The numerical CTSI has a maximum of ten points, and is the sum of the Balthazar grade points and pancreatic necrosis grade points:

Balthazar grade

Balthazar grade ՀՇ տվյալներ CT grade points
Grade A Normal CT 0 points
Grade B Focal or diffuse enlargement of the pancreas 1 point
Grade C Pancreatic gland abnormalities and peripancreatic inflammation 2 points
Grade D Fluid collection in a single location 3 points
Grade E Two or more fluid collections and / or gas bubbles in or adjacent to pancreas 4 points

Necrosis score

Necrosis percentage Points
No necrosis 0 points
0 to 30% necrosis 2 points
30 to 50% necrosis 4 points
Over 50% necrosis 6 points

CTSI's staging of acute pancreatitis severity has been shown by a number of studies to provide more accurate assessment than APACHE II, Ranson, and C-reactive protein (CRP) level.[7][8][9][10] However, a few studies indicate that CTSI is not significantly associated with the prognosis of hospitalization in patients with pancreatic necrosis, nor is it an accurate predictor of AP severity.[11][12]

Գլազգոյի սանդղակ

խմբագրել

Գլազգոյի սանդղակն օգտագործվում է և՛ լեղաքարերի, և՛ ալկոհոլի հետևանքով առաջացած պանկրեատիտների դեպքում, մինչդեռ Ռենսոնի սանդղակը կիրառելի է միայն ալկոհոլի հետևանքով առաջացած պանկրեատիտի դեպքում։ Եթե պացիենտի վիճակը գնահատվում է 3 և ավելի միավոր, նշանակում է առկա է ծանր աստիճանի պանկրեատիտ և պացիենտին պետք է տեղափոխել ինտենսիվ թերապիայի բաժանմումք։ Այս սանդղակով գնահատումն իրականացվում է «PANCREAS» եզրույթով․

  • P - PaO2 / թթվածնի պարցիալ ճնշում <8 կՊա
  • A - Age / տարիք >55
  • N - Neutrophilia / նեյտրոֆիլիա >15x10(9)/L
  • C - Calcium / կալցիում <2 մմոլ/լ
  • R - Renal function: Urea / երիկամային ֆունկցիա․միզանյութ >16 մմոլ/լ
  • E - Enzymes: / ֆերմենտներ լակտատդեհիդրոգենազա >600 միջ․միավ․/լ; ԱՍՏ >200միջ․ միավ․/լ
  • A - Albumin / ալբումին <32 գ/լ (շիճուկում)
  • S - Sugar: blood glucose / գլյուկոզ >10 մմոլ/լ

BISAP սանդղակ

խմբագրել

Predicts mortality risk in pancreatitis with fewer variables than Ranson's criteria. Data should be taken from the first 24 hours of the patient's evaluation.

  • Արյան մեջ միզանյութի քանակ >25 մգ/դլ (8.9 մմոլ/լ)
  • Abnormal mental status with a Glasgow coma score <15
  • Evidence of SIRS (systemic inflammatory response syndrome)
  • Տարիքը > 60
  • ՀՇ–ով հայտնաբերվում է հեղուկ թոքամզի խոռոչում

Patients with a score of zero had a mortality of less than one percent, whereas patients with a score of five had a mortality rate of 22 percent. In the validation cohort, the BISAP score had similar test performance characteristics for predicting mortality as the APACHE II score.[13] As is a problem with many of the other scoring systems, the BISAP has not been validated for predicting outcomes such as length of hospital stay, need for ICU care, or need for intervention.

Համաճարակաբանություն

խմբագրել

ԱՄՆ-ում տարեկան դեպքերը 18-ն են 100,000 բնակչության համար, իսկ հոսպիտալացման դեպքերը 220,000 են[14]: Ըստ եվրոպական հետազոտության, 1985–1995թթ–ներին սուր պանկրեատիտի դեպքերի տարեկան հաճախականությունը 12.4–ից դարձել է 15.9՝ 100,000 մարդու հաշվարկով[15]։

Արևմտյան երկրներում սուր պանկրեատիտի հիմնական պատճառն ալկոհոլն է․ ԱՄՆ–ում՝ 65%, Շվեդիայում՝ 20%, Միացյալ Թագավորությունում՝ 5%։ Արևելյան երկրներում հիմնական պատճառը լեղաքարերն են։ Սուր պանկրեատիտի պատճառները փոքր–ինչ տարբերվում են տարիքային խմբերի համար, օրինակ վնասվածքները և համակարգային հիվանդությունները որպես պատճառ ավելի հաճախ են երեխաների մոտ։ Խոզուկը (էպիդեմիկ պարօտիտ) ավելի հաճախադեպ պատճառ է դեռահասային տարիքում։





Հասարակություն և մշակույթ

խմբագրել

The way people view stillbirths has changed dramatically over time, however its economic and psychosocial impact is often underestimated.[16] In the early 20th century, when a stillbirth occurred, the baby was taken and discarded and the parents were expected to immediately let go of the attachment and try for another baby.[17] In many countries parents are expected by friends and family members to recover from the loss of an unborn baby very soon after it happens.[18] Societally-mediated complications such as financial hardship and depression are among the more common results.[18] A stillbirth can have significant psychological effects on the parents, notably causing feelings of guilt in the mother.[19]

Օրինական սահմանումներ

խմբագրել
In Japan, statues of Jizō, a Buddhist patron deity of children, memorialize stillborn babies.

Ավստրալիա

խմբագրել

Մեռելածնությունն Ավստրալիայում սահմանվում է հետևյալ կերպ․ երեխան ծնվում է առանց կյանքի նշանների, կշռում է ավելի քան 400 գրամ կամ հղիության 20–րդ շաբաթում է[20]։

Ավստրիա

խմբագրել

Երեխան կշռում է ամենաքիչը 500 գրամ և բացակայում են շնչառական, մկանային շարժումները, արյան շրջանառությունը։

Կանադա

խմբագրել

Beginning in 1959, "the definition of a stillbirth was revised to conform, in substance, to the definition of fetal death recommended by the World Health Organization."[21] The definition of "fetal death" promulgated by the World Health Organization in 1950 is as follows:

"Fetal death" means death prior to the complete expulsion or extraction from its mother of a product of human conception, irrespective of the duration of pregnancy and which is not an induced termination of pregnancy. The death is indicated by the fact that after such expulsion or extraction, the fetus does not breathe or show any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles. Heartbeats are to be distinguished from transient cardiac contractions; respirations are to be distinguished from fleeting respiratory efforts or gasps.[22]

Germany

խմբագրել
Monument to stillborn babies in Germany

In Germany, a stillbirth is defined as birth of a child of at least 500 g weight without blood circulation or breath. Details for burial vary amongst the federal states.[23]

Republic of Ireland

խմբագրել
At one time, this Angels' Plot was one of the few burial grounds for stillborn babies that was consecrated by the Catholic Church in Ireland.

Since 1 Jan 1995 stillbirths occurring in the Republic of Ireland must be registered; stillbirths which occurred before that date can also be registered but evidence is required.[24] For the purposes of civil registration, s.1 of the Stillbirths Registration Act 1994 refers to :-

"...a child weighing at least 500 grammes, or having reached a gestational age of at least 24 weeks who shows no signs of life."

The Netherlands

խմբագրել

In the Netherlands, stillbirth is defined differently by the central bureau of statistics (CBS) and the Dutch perinatal registry (Stichting PRN). The birth and mortality numbers from the CBS include all liveborn children, regardless of gestational duration and all stillbirths from 24 weeks of gestation and onwards. In the Perinatal Registry, gestational duration of both liveborn and stillborn children is available. They register all liveborn and stillborn children from 22, 24 or 28 weeks of gestation and onwards (dependent on the report: fetal, neonatal or perinatal mortality). Therefore, data from these institutions on (still)births can not simply be compared one-on-one.

United Kingdom

խմբագրել

The registration of still-births has been required in England and Wales from 1927, in Scotland from 1939 but is not required in Northern Ireland.[25] Sometimes a pregnancy is terminated deliberately during a late phase, for example for congenital anomaly. UK law requires these procedures to be registered as "stillbirths".[26]

England and Wales
խմբագրել

For the purposes of the Births and Deaths Registration Act 1926 (as amended), section 12 contains the definition that :-

"still-born" and "still-birth" shall apply to any child which has issued forth from its mother after the twenty fourth week of pregnancy and which did not at any time after being completely expelled from its mother, breathe or show any other signs of life.

A similar definition is applied within the Births and Deaths Registration Act 1953 (as amended), contained in s.41.

The above definitions apply within those Acts thus other legislation will not necessarily be in identical terms.

s.2 of the 1953 Act requires that registration of a birth takes place within 42 days of the birth except where an inquest takes place or the child has been "found exposed" in which latter case the time limit runs from the time of finding.

Extracts from the register of still-births are restricted to those who have obtained consent from the Registrar General for England and Wales.

Scotland
խմբագրել

Section 56(1) of the Registration of Births, Deaths and Marriages (Scotland) Act 1965 (as amended) contains the definition that :-

"still-born child" means a child which has issued forth from its mother after the twenty-fourth week of pregnancy and which did not at any time after being completely expelled from its mother breathe or show any other signs of life, and the expression "still-birth" shall be construed accordingly

s.21(1) of the same Act requires that :-

Except so far as otherwise provided by this section or as may be prescribed, the provisions of this Part of this Act shall, so far as applicable, apply to still-births in like manner as they apply to births of children born alive.

In the general case, s.14 of the Act requires that a birth has to be registered within 21 days of the birth or of the child being found.

Unlike the registers for births, marriages, civil partnerships and deaths, the register of still-births is not open to public access and issue of extracts requires the permission of the Registrar General for Scotland.

Northern Ireland
խմբագրել

In Northern Ireland, the Births and Deaths Registration (Northern Ireland) Order 1976,[27] as amended contains the definition :-

"still-birth" means the complete expulsion or extraction from its mother after the twenty-fourth week of pregnancy of a child which did not at any time after being completely expelled or extracted breathe or show any other evidence of life.

Registration of still-births can be made by a relative or certain other persons involved with the still-birth but it is not compulsory to do so. Registration takes place with the District Registrar for the Registration District where the still-birth occurred or for the District in which the mother is resident. A still-birth certificate will be issued to the registrant with further copies only available to those obtaining official consent for their issue. Registration may be made within three months of the still-birth[28]

ԱՄՆ

խմբագրել

ԱՄՆ–ում «մեռելածնություն» եզրույթի հստակ սահմանում չկա։[22]

In the U.S., the Born-Alive Infants Protection Act of 2002 specifies that any breathing, heartbeat, pulsating umbilical cord, or confirmed voluntary muscle movement indicate live birth rather than stillbirth.[29]

The Centers for Disease Control and Prevention collects statistical information on "live births, fetal deaths, and induced termination of pregnancy" from 57 reporting areas in the United States. Each reporting area has different guidelines and definitions for what is being reported; many do not use the term "stillbirth" at all. The federal guidelines suggest (at page 1) that fetal death and stillbirth can be interchangeable terms. The CDC definition of "fetal death" is based on the definition promulgated by the World Health Organization in 1950 (see section above on Canada). Researchers are learning more about the long term psychiatric sequelae of traumatic birth and believe the effects may be intergenerational[30]

The federal guidelines recommend reporting those fetal deaths whose birth weight is over 12.5 oz (350 g), or those more than 20 weeks gestation. Forty-one areas use a definition very similar to the federal definition, thirteen areas use a shortened definition of fetal death, and three areas have no formal definition of fetal death. Only 11 areas specifically use the term 'stillbirth', often synonymously with late fetal death, however they are split between whether stillbirths are "irrespective of the duration of pregnancy", or whether some age or weight constraint is applied. A movement in the U.S. has changed the way that stillbirths are documented through vital records. Previously, only the deaths were reported. However 27 states have enacted legislation that offers some variation of a birth certificate as an option for parents who choose to pay for one. Parents may not claim a tax exemption for stillborn infants, even if a birth certificate is offered. To claim an exemption, the birth must be certified as live, even if the infant only lives for a very brief period.

Արտաքին հղումներ

խմբագրել
  1. ↑ Larvin M, McMahon MJ (July 1989). «APACHE-II score for assessment and monitoring of acute pancreatitis». Lancet. 2 (8656): 201–5. doi:10.1016/S0140-6736(89)90381-4. PMID 2568529.
  2. ↑ Yeung YP, Lam BY, Yip AW (May 2006). «APACHE system is better than Ranson system in the prediction of severity of acute pancreatitis». Hepatobiliary & Pancreatic Diseases International. 5 (2): 294–9. PMID 16698595. Արխիվացված է օրիգինալից 2006-10-26-ին.
  3. ↑ 3,0 3,1 Chatzicostas C, Roussomoustakaki M, Vlachonikolis IG, Notas G, Mouzas I, Samonakis D, Kouroumalis EA (November 2002). «Comparison of Ranson, APACHE II and APACHE III scoring systems in acute pancreatitis». Pancreas. 25 (4): 331–5. doi:10.1097/00006676-200211000-00002. PMID 12409825. (comment=this study used a Apache cutoff of >=10)
  4. ↑ 4,0 4,1 Banks PA, Freeman ML, և այլք: (Practice Parameters Committee of the American College of Gastroenterology) (October 2006). «Practice guidelines in acute pancreatitis». The American Journal of Gastroenterology. 101 (10): 2379–400. doi:10.1111/j.1572-0241.2006.00856.x. PMID 17032204.
  5. ↑ UK Working Party on Acute Pancreatitis (May 2005). «UK guidelines for the management of acute pancreatitis». Gut. 54 Suppl 3 (Suppl 3): iii1–9. doi:10.1136/gut.2004.057026. PMC 1867800. PMID 15831893.
  6. ↑ Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH (February 1990). «Acute pancreatitis: value of CT in establishing prognosis». Radiology. 174 (2): 331–6. doi:10.1148/radiology.174.2.2296641. PMID 2296641.
  7. ↑ Gürleyik G, Emir S, Kiliçoglu G, Arman A, Saglam A (November 2005). «Computed tomography severity index, APACHE II score, and serum CRP concentration for predicting the severity of acute pancreatitis». JOP. 6 (6): 562–7. PMID 16286706.
  8. ↑ Knoepfli AS, Kinkel K, Berney T, Morel P, Becker CD, Poletti PA (2007). «Prospective study of 310 patients: can early CT predict the severity of acute pancreatitis?» (PDF). Abdominal Imaging. 32 (1): 111–5. doi:10.1007/s00261-006-9034-y. PMID 16944038.
  9. ↑ Leung TK, Lee CM, Lin SY, Chen HC, Wang HJ, Shen LK, Chen YY (October 2005). «Balthazar computed tomography severity index is superior to Ranson criteria and APACHE II scoring system in predicting acute pancreatitis outcome». World Journal of Gastroenterology. 11 (38): 6049–52. doi:10.3748/wjg.v11.i38.6049. PMC 4436733. PMID 16273623.{{cite journal}}: CS1 սպաս․ չպիտակված ազատ DOI (link)
  10. ↑ Vriens PW, van de Linde P, Slotema ET, Warmerdam PE, Breslau PJ (October 2005). «Computed tomography severity index is an early prognostic tool for acute pancreatitis». Journal of the American College of Surgeons. 201 (4): 497–502. doi:10.1016/j.jamcollsurg.2005.06.269. PMID 16183486.
  11. ↑ Triantopoulou C, Lytras D, Maniatis P, Chrysovergis D, Manes K, Siafas I, Papailiou J, Dervenis C (October 2007). «Computed tomography versus Acute Physiology and Chronic Health Evaluation II score in predicting severity of acute pancreatitis: a prospective, comparative study with statistical evaluation». Pancreas. 35 (3): 238–42. doi:10.1097/MPA.0b013e3180619662. PMID 17895844.
  12. ↑ Mortelé KJ, Mergo PJ, Taylor HM, Wiesner W, Cantisani V, Ernst MD, Kalantari BN, Ros PR (October 2004). «Peripancreatic vascular abnormalities complicating acute pancreatitis: contrast-enhanced helical CT findings». European Journal of Radiology. 52 (1): 67–72. doi:10.1016/j.ejrad.2003.10.006. PMID 15380848.
  13. ↑ Papachristou GI, Muddana V, Yadav D, O'Connell M, Sanders MK, Slivka A, Whitcomb DC (February 2010). «Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis». The American Journal of Gastroenterology. 105 (2): 435–41, quiz 442. doi:10.1038/ajg.2009.622. PMID 19861954.
  14. ↑ Whitcomb DC (May 2006). «Clinical practice. Acute pancreatitis». The New England Journal of Medicine. 354 (20): 2142–50. doi:10.1056/NEJMcp054958. PMID 16707751.
  15. ↑ Eland IA, Sturkenboom MJ, Wilson JH, Stricker BH (October 2000). «Incidence and mortality of acute pancreatitis between 1985 and 1995». Scandinavian Journal of Gastroenterology. 35 (10): 1110–6. doi:10.1080/003655200451261. PMID 11099067.
  16. ↑ Heazell, Alexander E P; Siassakos, Dimitrios; Blencowe, Hannah; Burden, Christy; Bhutta, Zulfiqar A; Cacciatore, Joanne; Dang, Nghia; Das, Jai; Flenady, Vicki; Gold, Katherine J; Mensah, Olivia K; Millum, Joseph; Nuzum, Daniel; O'Donoghue, Keelin; Redshaw, Maggie; Rizvi, Arjumand; Roberts, Tracy; Toyin Saraki, H E; Storey, Claire; Wojcieszek, Aleena M; Downe, Soo (2016). «Stillbirths: economic and psychosocial consequences» (PDF). The Lancet. 387 (10018): 604–616. doi:10.1016/S0140-6736(15)00836-3. ISSN 0140-6736. PMID 26794073.
  17. ↑ Cooper, J. D. (1980). «Parental Reactions to Stillbirth». The British Journal of Social Work. 10 (1): 55–69. doi:10.1093/oxfordjournals.bjsw.a054495. Earle, S.; Komaromy, C.; Layne, L., eds. (2012). Understanding reproductive loss: perspectives on life, death and fertility. Ashgate Publishing Ltd. ISBN 978-1-4094-2810-7. Արխիվացված օրիգինալից 2017-03-19-ին.
  18. ↑ 18,0 18,1 Քաղվածելու սխալ՝ Սխալ <ref> պիտակ՝ «
    03» անվանումով ref-երը տեքստ չեն պարունակում:
  19. ↑ Քաղվածելու սխալ՝ Սխալ <ref> պիտակ՝ «Rob20142» անվանումով ref-երը տեքստ չեն պարունակում:
  20. ↑ Lahra MM, Gordon A, Jeffery HE (2007). «Chorioamnionitis and fetal response in stillbirth». Am. J. Obstet. Gynecol. 196 (3): 229.e1–4. doi:10.1016/j.ajog.2006.10.900. PMID 17346531. «Stillbirth is defined within Australia as fetal death (no signs of life), whether antepartum or intrapartum, at ≥20 weeks of gestation or ≥400 g birthweight, if gestational age is unknown.»
  21. ↑ Statistics Canada ("Canada's National Statistical Agency"), History, Vital Statistics - Stillbirth Database, in Vital Statistics – Stillbirth Database Արխիվացված Մայիս 5, 2007 Wayback Machine.
  22. ↑ 22,0 22,1 Centers for Disease Control and Prevention. State Definitions and Reporting Requirements (PDF) (1997 Revision ed.). National Center for Health Statistics. Արխիվացված (PDF) օրիգինալից 2017-08-29-ին.
  23. ↑ «Gesetze». Initiative-regenbogen.de. Արխիվացված է օրիգինալից 2013-07-13-ին. Վերցված է 2013-08-06-ին.
  24. ↑ «Registering a stillbirth». citizensinformation.ie. Արխիվացված օրիգինալից 7 February 2009-ին. Վերցված է 15 January 2017-ին.
  25. ↑ «Archived copy». Արխիվացված է օրիգինալից 2012-03-27-ին. Վերցված է 2012-03-18-ին.{{cite web}}: CS1 սպաս․ արխիվը պատճենվել է որպես վերնագիր (link)
  26. ↑ Bythell M; և այլք: (2008). «The contribution of late termination of pregnancy to stillbirth rates in Northern England, 1994-2005». The British Journal of Obstetrics and Gynaecology. 115 (5): 664–666. doi:10.1111/j.1471-0528.2008.01668.x. PMID 18333949.
  27. ↑ «Births and Deaths Registration (Northern Ireland) Order 1976». Legislation.gov.uk. Արխիվացված օրիգինալից 2013-05-23-ին. Վերցված է 2013-08-06-ին.
  28. ↑ NI Direct - Registering a Still-birth Արխիվացված 2012-03-27 Wayback Machine
  29. ↑ «House Report 107-186 - BORN-ALIVE INFANTS PROTECTION ACT OF 2001». gpo.gov. Արխիվացված օրիգինալից 16 October 2006-ին. Վերցված է 15 January 2017-ին.
  30. ↑ Cacciatore J (2010). «Unique stories of women and their families after the death of a baby». Journal of Healthcare Social Work. 49 (2): 134–148. doi:10.1080/00981380903158078. hdl:2286/R.I.28317. PMID 20175019.

Վիլլեբրանդի հիվանդություն

խմբագրել

Վոն Վիլլեբրանդի հիվանդություն (vWD), արյան մակարդման ժառանգական հիվանդություններից ամենատարածվածն է։ Ձեռքբերովի տեսակը կարող է առաջանալ այլ ախտաբանությունների պատճառով[1]։ Առաջանում է Վիլլեբրանդի գործոնի որակական կամ քանակական անբավարարությունից․ գործոնը մուլտիմեր սպիտակուց է, անհրաժեշտ թրոմբոցիտների ադհեզիայի համար։ Վիլլեբրանդի հիվանդության երեք հիմնական տեսակներն են ժառանգականը, ձեռքբերովին և թրոմբոցիտայինը։ Ժառանգականն ունի երեք ենթատեսակ՝ I, II, III[2]։ Platelet type vWD is also an inherited condition.[3] In 2008 a new diagnostic category of "Low VWF" was proposed to include those individuals whose Von Willebrand Factor levels were below the normal reference range but not low enough to be Von Willebrand Disease (levels in the 30-50 IU/dL range).[4]

Patients with Low VWF can experience bleeding, despite mild reductions in VWF levels.[5] vWD type 1 is the most common type of the disorder, with mild bleeding symptoms such as nosebleeds and occasionally more severe symptoms can occur. Blood type can affect the presentation and severity of symptoms of vWD.[6]

II ենթատեսակը ամենահաճախ հանդիպողն է և ախտանշանները լինում են թույլ և միջին։ Անվանակոչվել է ֆինն բժիշկ Էրիկ Ադոլֆ վոն Վիլլեբրանդի պատվին, որը 1926թվականին առաջին անգամ նկարգրել է հիվանդությունը։

Ախտանշաններ

խմբագրել

Տարբեր տեսակների դեպքում արյան կորուստը տարբեր է՝ կապտուկներ, քթային և/կամ լնդային արյունահոսություններ։ Կանանց մոտ կարող են լինել առատ դաշտան և արյան կորուստ ծննդաբերության ժամանակ[7][8]։

Ներքին առատ արյունահոսությունները բնորոշ են III ենթատեսակին։

Ժառանգականություն

խմբագրել

Վիլլեբրանդի գործոնի գենը տեղակայված է 12–րդ քրոմոսոմի կարճ՝ p թևում։ I և II ենթատեսակները հիմնականում ժառանգվում են աուտոսոմ դոմինանտ, իսկ III ենթատեսակը՝ աուտոսոմ ռեցեսիվ։ Հիվանդությունը հանդիպում է բնակչության 1%–ի մոտ, տղամարդկանց և կանանց ախտահարում է հավասարապես[9]։

Ախտաֆիզիալոգիա

խմբագրել

Von Willebrand factor is mainly active in conditions of high blood flow and shear stress. Deficiency of vWF, therefore, shows primarily in organs with extensive small vessels, such as skin, gastrointestinal tract, and uterus. In angiodysplasia, a form of telangiectasia of the colon, shear stress is much higher than in average capillaries, and the risk of bleeding is increased concomitantly.

In more severe cases of type 1 vWD, genetic changes are common within the vWF gene and are highly penetrant. In milder cases of type 1 vWD, a complex spectrum of molecular pathology may exist in addition to polymorphisms of the vWF gene alone.[10] The individual's ABO blood group can influence presentation and pathology of vWD. Those individuals with blood group O have a lower mean level than individuals with other blood groups. Unless ABO group–specific vWF:antigen reference ranges are used, normal group O individuals can be diagnosed as type I vWD, and some individuals of blood group AB with a genetic defect of vWF may have the diagnosis overlooked because vWF levels are elevated due to blood group.[11]

Ախտորոշում

խմբագրել

When vWD is suspected, blood plasma of a patient must be investigated for quantitative and qualitative deficiencies of vWF. This is achieved by measuring the amount of vWF in a vWF antigen assay and the functionality of vWF with a glycoprotein (GP)Ib binding assay, a collagen binding assay, or a ristocetin cofactor activity (RiCof) or ristocetin-induced platelet agglutination (RIPA) assays. Factor VIII levels are also performed because factor VIII is bound to vWF which protects the factor VIII from rapid breakdown within the blood. Deficiency of vWF can then lead to a reduction in factor VIII levels, which explains the elevation in PTT. Normal levels do not exclude all forms of vWD, particularly type 2, which may only be revealed by investigating platelet interaction with subendothelium under flow, a highly specialized coagulation study not routinely performed in most medical laboratories. A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A platelet function assay may give an abnormal collagen/epinephrine closure time, and in most cases, a normal collagen/ADP time. Type 2N may be considered if factor VIII levels are disproportionately low, but confirmation requires a "factor VIII binding" assay. Additional laboratory tests that help classify sub-types of vWD include von-willebrand multimer analysis, modified ristocetin induced platelet aggregation assay and vWF propeptide to vWF antigen ratio propeptide. In cases of suspected acquired von-Willebrand syndrome, a mixing study (analysis of patient plasma along with pooled normal plasma/PNP and a mixture of the two tested immediately, at one hour, and at two hours) should be performed.[12] Detection of vWD is complicated by vWF being an acute-phase reactant with levels rising in infection, pregnancy, and stress.

Other tests performed in any patient with bleeding problems are a complete blood count-CBC (especially platelet counts), activated partial thromboplastin time-APTT, prothrombin time with International Normalized Ratio-PTINR, thrombin time-TT, and fibrinogen level. Testing for factor IX may also be performed if hemophilia B is suspected. Other coagulation factor assays may be performed depending on the results of a coagulation screen. Patients with von Willebrand disease typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.

The testing for vWD can be influenced by laboratory procedures. Numerous variables exist in the testing procedure that may affect the validity of the test results and may result in a missed or erroneous diagnosis. The chance of procedural errors are typically greatest during the preanalytical phase (during collecting storage and transportation of the specimen) especially when the testing is contracted to an outside facility and the specimen is frozen and transported long distances.[13] Diagnostic errors are not uncommon, and the rate of testing proficiency varies amongst laboratories, with error rates ranging from 7 to 22% in some studies to as high as 60% in cases of misclassification of vWD subtype. To increase the probability of a proper diagnosis, testing should be done at a facility with immediate on-site processing in a specialized coagulation laboratory.[14][15]

Տեսակներ

խմբագրել

The four hereditary types of vWD described are type 1, type 2, type 3, and pseudo- or platelet-type. Most cases are hereditary, but acquired forms of vWD have been described. The International Society on Thrombosis and Haemostasis's classification depends on the definition of qualitative and quantitative defects.[16]

 
von Willebrand disease type III (and sometimes II) is inherited in an autosomal recessive pattern.

Տեսակ 1

խմբագրել

Այս տեսակը Type 1 vWD (60-80% of all vWD cases) is a quantitative defect which is heterozygous for the defective gene. It can arise from failure to secrete vWF into the circulation or from vWF being cleared more quickly than normal. Decreased levels of vWF are detected at 20-50% of normal, i.e. 20-50 IU. [9]

Շատ պացիենտների մոտ ախտանշանները կամ բացակայում են, կամ էլ թույլ են արտահայտված։ Այդ պատճառով էլ շատ հաճախ հիվանդության այս տեսակը հնարավոր է չախտորոշել մինչև կյանքի վերջ։ Հիվանդությունը կարող է բացահայտվել այլ բժշկական միջամտությունների ժամանակ, օրինակ վիրահատությունների կամ ատամի հեռացման դեպքում արյունահոսություններ, ինչպես նաև կապտուկների արագ առաջացում, մենոռագիա (առատ դաշտան)։ Միայն փոքր մասի մոտ են հնարավոր առատ արյունահոսություններ։

Տեսակ 2

խմբագրել

Այս տեսակը (15-30% դեպքերում) պայմանավորված է գործոնի որակական փոփոխությամբ, և արյունահոսության քանակը տարբեր մարդկանց մոտ տարբեր է։ Ունի 4 ենթատեսակ՝ 2A, 2B, 2M, and 2N[9]։

Տեսակ 2A
խմբագրել

The ability of the qualitatively defective von Willebrand factors to coalesce and form large vWF multimers is impaired, resulting in decreased quantity of large vWF multimers and low RCoF activity. Only small multimer units are detected in the circulation. Von Willebrand factor antigen (vWF:Ag) assay is low or normal.

Տեսակ 2B
խմբագրել

This is a "gain of function" defect. The ability of the qualitatively defective vWF to bind to glycoprotein Ib (GPIb) receptor on the platelet membrane is abnormally enhanced, leading to its spontaneous binding to platelets and subsequent rapid clearance of the bound platelets and of the large vWF multimers. Thrombocytopenia may occur. Large vWF multimers are reduced or absent from the circulation.

The ristocetin cofactor activity is low when the patient's platelet-poor plasma is assayed against formalin-fixed, normal donor platelets. However, when the assay is performed with the patient's own platelets (platelet-rich plasma), a lower-than-normal amount of ristocetin causes aggregation to occur. This is due to the large vWF multimers remaining bound to the patient's platelets. Patients with this subtype are unable to use desmopressin as a treatment for bleeding, because it can lead to unwanted platelet aggregation and aggravation of thrombocytopenia.

տեսակ 2M
խմբագրել

Type 2M vWD is a qualitative defect of vWF characterized by its decreased ability to bind to GPIb receptor on the platelet membrane and normal capability at multimerization. The vWF antigen levels are normal. The ristocetin cofactor activity is decreased and high molecular weight large vWF multimers are present in the circulation.[17]

Type 2N (Normandy)
խմբագրել

This is a deficiency of the binding of vWF to coagulation factor VIII. The vWF antigen test is normal, indicating normal quantity of vWF. The ristocetin cofactor assay is normal. Assay for coagulation factor VIII revealed marked quantitative decrease equivalent to levels seen in hemophilia A. This has led to some vWD type 2N patients being misdiagnosed as having hemophilia A.

Type 3

խմբագրել

Type 3 is the most severe form of vWD (homozygous for the defective gene) and is characterized by complete absence of production of vWF. The von Willebrand factor is undetectable in the vWF antigen assay. Since the vWF protects coagulation factor VIII from proteolytic degradation, total absence of vWF leads to extremely low factor VIII level, equivalent to that seen in severe hemophilia A with its clinical manifestations of life-threatening external and internal hemorrhages. The inheritance pattern of vWD type 3 is autosomal recessive, while the inheritance pattern of hemophilia A is X-linked recessive.

Platelet-type

խմբագրել

Platelet-type vWD (also known as pseudo-vWD) is an autosomal dominant genetic defect of the platelets. The vWF is qualitatively normal and genetic testing of the von Willebrand gene and vWF protein reveals no mutational alteration. The defect lies in the qualitatively altered GPIb receptor on the platelet membrane which increases its affinity to bind to the vWF. Large platelet aggregates and high molecular weight vWF multimers are removed from the circulation resulting in thrombocytopenia and diminished or absent large vWF multimers. The ristocetin cofactor activity and loss of large vWF multimers are similar to vWD type 2B.

Acquired

խմբագրել

Acquired vWD can occur in patients with autoantibodies. In this case, the function of vWF is not inhibited, but the vWF-antibody complex is rapidly cleared from the circulation.

A form of vWD occurs in patients with aortic valve stenosis, leading to gastrointestinal bleeding (Heyde's syndrome). This form of acquired vWD may be more prevalent than is presently thought. In 2003, Vincentelli et al. noted that patients with acquired vWD and aortic stenosis who underwent valve replacement experienced a correction of their hemostatic abnormalities, but that the hemostatic abnormalities can recur after 6 months when the prosthetic valve is a poor match with the patient.[18] Similarly, acquired vWD contributes to the bleeding tendency in people with an implant of a left ventricular assist device (a pump that pumps blood from the left ventricle of the heart into the aorta).[19]


Դիկլոֆենակ

խմբագրել

Դիկլոֆենակ, վաճառքային անունը «Վոլտարեն», ոչ ստերոիդային հակաբորբոքային դեղ (ՈՍՀԲԴ), օգտագործվում է բորբոքային հիվանդությունների, օրինակ հոդատապի դեպքում ցավի մեղմացման համար[20]։ Կիրառվում է պեր օրալ հաբերի, ներարկման կամ քսուքների ձևով[20][21]։ Ցավը վերանում է օգտագործումից մոտ մեկուկես ժամ անց, և ցավազրկումը պահպանվում է մոտ ութ ժամ[20]։ Հասանելի է նաև միսոպրոստոլի հետ կոմբինացիայով, կիրառվում է ստամոքսի խնդիրների դեպքում[22]։

Հիմնական կողմնակի ազդեցություններն են որովայնային ցավերը, ստամոքսաղիքային ուղու արյունահոսությունները, սրտխառնոցը, գլխացավը, գլխապտույտը, այտուցները[20]։ Լուրջ կողմնակի ազդեցությունները ներառում են սրտային անբավարարությունը, կաթվածը, երիկամային խնդիրները, ստամոքսի խոցը[22][20]։ Խորհուրդ չի տրվում օգտագործել հղիության երրորդ եռամսյակում[20], իսկ կրծքով կերակրման ժամանակ օգտագործումն անվտանգ է[22]։ Ենթադրվում է, որ նվազեցնում է պրոստագլանդինի արտադրությունը[23]։ Արգելակում է ցիկլոօքսիգենազ–1 (ՑՕԳ-1) և ցիկլոօքսիգենազ–2 (ՑՕԳ-2) ֆերմենտները[20]։

Դիկլոֆենակը պատենտավորվել է 1965թ–ին, ԱՄՆ–ում բժշկական կիրառությունը սկսվել է 1988թ–ին[20][24]։ It is available as a generic medication.[20]

Diclofenac was patented in by Ciba-Geigy; it came into medical use in the United States in . The wholesale cost in the developing world is generally less than US$2 per month as of 2015.[25] In the United States the wholesale cost of this amount is typically less than US$9 as of 2018.[26] In 2017, it was the 94th most commonly prescribed medication in the United States, with more than eight million prescriptions.[27][28] Հասանելի է և՛ նատրիումի, և՛ կալիումի աղերի տեսքով[22]։

Բժշկական կիրառություն

խմբագրել

Կիրառվում է ցավի, բորբոքային հիվանդությունների, դիսմենորեայի բուժման համար[29]։

Ցավ

խմբագրել

Բորբոքային գործընթացները կարող են ներառել ոսկրամկանային բարդություններ, հատկապես՝ արթրիտ, ռևմատոիդ արթրիտ, պոլիմիոզիտ, դերմատոմիոզիտ, ատամնացավ, քունք–ստործնոտային կապանի ցավ, սպոնդիլոարթրիտ, անկիլոզացնող սպոնդիլիտ, հոդատապի գրոհներ[30], նաև ցավի կառավարումը երիկամային կամ լեղային քարերի դեպքում։ Կիրառման մյուս ցուցում է համարվում սուր միգրենը[31]։ Դիկլոֆենակը սովորաբար օգտագործվում է հետվնասվածքային, հետվիրահատական մեղմ և միջին աստիճանի ցավերի դեպքում, հատկապես եթե առկա է նաև բորբոքում[30]։ Արդյունավետ է դաշտանային ցավերի և էնդոմետրիոզի ժամանակ։

Դիկլոֆենակը հասանելի է նաև տեղային կիրառման դեղաձևերով, և արդյունավետ է օստեորաթրիտի, և ոչ այլ ոսկրամկանային ցավերի համար[32]։

Կարող է օգտակար լինել նաև ակտինիկ կերատոզի ժամանակ, ինչպես նաև կապանների վնասումից առաջացած սուր ցավերի դեպքում[33]։

Շատ երկրներում դիկլոֆենակն աչքի կաթիլների ձևով օգտագործվում է աչքի առաջային մասի սուր և քրոնիկ ոչ բակտերիալ բորբոքման բուժման համար[34]։ Դիկլոֆենակի աչքի կաթիլները կիրառվում են եղջերաթաղանթի քերծվածքների դեպքում ցավի կառավարման համար[35]։

Դիկլոֆենակը հաճախ օգտագործվում է քաղցկեղի առկայության դեպքում ցավազրկման համար, հատկապես եթե առկա է նաև բորբոքում[36]։ Կարող է կիրառվել

օփիոիդների հետ համակցված, օրինակ՝ դիկլոֆենակ և կոդեին։

Հակացուցումներ

խմբագրել
  • Գերզգայունություն դիկլոֆենակի նկատմամբ
  • ՈՍՀԲԴ–ների (օրինակ՝ ասպիրին) կիրառումից հետո ալերգիկ ռեակցիաներ (շոկ, բրոնխասպազմ, ռինիտ, եղնջացան)
  • Հղիության երրորդ եռամսյակ
  • Խոցային հիվանդություն կամ արյունահոսություններ ստամոքսաղիքային համակարգից
  • Աղիների բորբոքային հիվանդություններ՝ Կրոնի հիվանդություն, խոցային կոլիտ
  • Սուր սրտային անբավարարություն (NYHA III / IV)
  • Pain management in the setting of coronary artery bypass graft (CABG) surgery
  • Ծանր լյարդային անբավարարություն
  • Ծանր քրոնիկ երիկամային անբավարարություն (creatinine clearance <30 ml/min)
  • Caution in patients with pre-existing hepatic porphyria, as diclofenac may trigger attacks
  • Caution in patients with severe, active bleeding such as cerebral hemorrhage
  • առհասարակ ՈՍՀԲԴ–երը չպետք է օգտագործվեն մլակային տենդի դեպքում, քանի որ դրանք հանգեցնում են մազանոթային թափանցելիության բարձրացման, սրտային անբավարարության
  • Caution in patients with fluid retention or heart failure
  • կարող է հանգեցնել նոր հիպերտենզիայի զարգացման կամ գոյություն ունեցող հիպերտենզիայի ընթացքի վատթարացման
  • կարող է առաջացնել մաշկային լուրջ խնդիրներ՝ էքսֆոլիատիվ դերմատիտ, Սթիվենս–Ջոնսոնի համախտանիշ, տոքսիկ էպիդերմալ նեկրոլիզ (վերջինս կարող է լինել մահացու)[37]

Կողմնակի ազդեցություններ

խմբագրել

Դիկլոֆենակի սպառումը հանգեցրել է սիրտ–անոթային համակարգի խնդիրների քանակի զգալի աճի․ հետազոտությունը ներառել է դիկլոֆենակը, իբուպրոֆենը, նապրօքսենը[38]։ Նկարագրվել են նաև ստամոքսաղիքային ուղու վերին հատվածների խնդիրներ[38]։

Դiclofenac consumption has been associated with significantly increased vascular and coronary risk in a study including coxib, diclofenac, ibuprofen and naproxen. Upper gastrointestinal complications were also reported. Major adverse cardiovascular events (MACE) were increased by about a third by diclofenac, chiefly due to an increase in major coronary events.[38] Compared with placebo, of 1000 patients allocated to diclofenac for a year, three more had major vascular events, one of which was fatal.[38] Vascular death was increased significantly by diclofenac.[38]

Սիրտանոթային համակարգ

խմբագրել

In 2013, a study found major vascular events were increased by about a third by diclofenac, chiefly due to an increase in major coronary events.[38] Compared with placebo, of 1000 people allocated to diclofenac for a year, three more had major vascular events, one of which was fatal.[38] Vascular death was increased by diclofenac (1·65).[38]

Following the identification of increased risks of heart attacks with the selective COX-2 inhibitor rofecoxib in 2004, attention has focused on all the other members of the NSAIDs group, including diclofenac. Research results are mixed, with a meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to nonusers.[39] Professor Peter Weissberg, Medical Director of the British Heart Foundation said, "However, the increased risk is small, and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms". Only aspirin was found not to increase the risk of heart disease; however, this is known to have a higher rate of gastric ulceration than diclofenac. In Britain the Medicines and Healthcare Products Regulatory Agency (MHRA) said in June 2013 that the drug should not be used by people with serious underlying heart conditions—people who had suffered heart failure, heart disease or a stroke were advised to stop using it completely.[40] As of January 15, 2015 the MHRA announced that diclofenac will be reclassified as a prescription-only medicine (POM) due to the risk of cardiovascular adverse events.[41]

A subsequent large study of 74,838 Danish users of NSAIDs or coxibs found no additional cardiovascular risk from diclofenac use.[42] A very large study of 1,028,437 Danish users of various NSAIDs or coxibs found the "Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk."[43]

Diclofenac is similar in COX-2 selectivity to celecoxib.[44]

Ստամոքսաղիքային համակարգ

խմբագրել
  • Ստամոքսաղիքային խնդիրներն ամենահաճախ գանգատներից են։ Խոցի զարգացման և/կամ արյունահոսության դեպքում հարկավոր է անհապաղ դադարեցնել դիկլոֆենակով բուժումը։ Երկար թերապիայի ընթացքում շատ պացիենտներ պրոֆիլակտիկ ընդունում են գաստրոպրոտեկտիվ դեղեր (միսոպրոստոլ, ռանիտիդին, օմեպրազոլ)։

Լյարդ

խմբագրել
  • Liver damage occurs infrequently, and is usually reversible. Hepatitis may occur rarely without any warning symptoms and may be fatal. Patients with osteoarthritis more often develop symptomatic liver disease than patients with rheumatoid arthritis. Liver function should be monitored regularly during long-term treatment. If used for the short-term treatment of pain or fever, diclofenac has not been found more hepatotoxic than other NSAIDs.
  • As of December 2009, Endo, Novartis, and the US FDA notified healthcare professionals to add new warnings and precautions about the potential for elevation in liver function tests during treatment with all products containing diclofenac sodium.[45]
  • Cases of drug-induced hepatotoxicity have been reported in the first month, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.
  • Physicians should measure transaminases periodically in patients receiving long-term therapy with diclofenac. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 week after initiating treatment with diclofenac.

Միզային համակարգ

խմբագրել
  • NSAIDs "are associated with adverse renal [kidney] effects caused by the reduction in synthesis of renal prostaglandins"[46] in sensitive persons or animal species, and potentially during long-term use in nonsensitive persons if resistance to side effects decreases with age. However, this side effect cannot be avoided merely by using a COX-2 selective inhibitor because, "Both isoforms of COX, COX-1 and COX-2, are expressed in the kidney... Consequently, the same precautions regarding renal risk that are followed for nonselective NSAIDs should be used when selective COX-2 inhibitors are administered."[46] However, diclofenac appears to have a different mechanism of renal toxicity.
  • Studies in Pakistan showed diclofenac caused acute kidney failure in vultures when they ate the carcasses of animals that had recently been treated with it. Drug-sensitive species and individual humans are initially assumed to lack genes expressing specific drug detoxification enzymes.[47]

Հոգեկան առողջություն

խմբագրել
  • Նյարդային համակարգի վրա նկարագրված կողմնակի ազդեցությունները թեև հազվադեպ են, բայց ներառվում են կողմնակի ազդեցությունների մեջ, քանի որ հանդիպում են նշանակալի չափով։ Այսպիսի կողմնակի ազդեցություններն են դեպրեսիան, ընկճախտը, գիշերային մղձավանջները, փսիխոտիկ ռեակցիաները և դյուրագրգռությունը[48]։

Ազդեցության մեխանիզմ

խմբագրել

Դեղի հակաբորբոքային, ջերմիջեցնող, ցավազրկող ազդեցությունների առաջացման հիմնական մեխանիզմը պրոստագլանդինների սինթեզի The primary mechanism responsible for its anti-inflammatory, antipyretic, and analgesic action is thought to be inhibition of prostaglandin synthesis by inhibition of the transiently expressed prostaglandin-endoperoxide synthase-2 (PGES-2) also known as cycloxygenase-2 (COX-2). It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.[49]

Research and an updated reveal of mechanism of action of diclofenac shows, that its action is as with all NSAIDs by inhibition of prostaglandin synthesis. Important is that diclofenac inhibits COX-1 and COX-2 with relative equipotency.

The action of one single dose is much longer (6 to 8 hr) than the very short 1.2–2 hr half-life of the drug would indicate. This could be partly because it persists for over 11 hours in synovial fluids.[50]

Diclofenac may also be a unique member of the NSAIDs. Some evidence indicates it inhibits the lipoxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). It also may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain its high potency - it is the most potent NSAID on a broad basis.[51]

Marked differences exist among NSAIDs in their selective inhibition of the two subtypes of cyclooxygenase, COX-1 and COX-2.[52] Much pharmaceutical drug design has attempted to focus on selective COX-2 inhibition as a way to minimize the gastrointestinal side effects of NSAIDs such as aspirin. In practice, use of some COX-2 inhibitors with their adverse effects has led to massive numbers of patient family lawsuits alleging wrongful death by heart attack, yet other significantly COX-selective NSAIDs, such as diclofenac, have been well tolerated by most of the population.

Besides the COX-inhibition, a number of other molecular targets of diclofenac possibly contributing to its pain-relieving actions have recently been identified. These include:

  • Blockage of voltage-dependent sodium channels (after activation of the channel, diclofenac inhibits its reactivation also known as phase inhibition)
  • Blockage of acid-sensing ion channels (ASICs)[53]
  • Positive allosteric modulation of KCNQ- and BK-potassium channels (diclofenac opens these channels, leading to hyperpolarization of the cell membrane)Society and culture

Cost

խմբագրել

In the United States the NADAC per dose is less than US$0.15 as of 2018 for 50 mg and 75 mg tablets.[54] The average wholesale cost in the United States in 2019 is about US$50 to $US100 per month at a typical dose.[55]

History

խմբագրել

In the United States, 1% diclofenac gel was approved by the FDA in 2007. It was approved as a prescription drug and was indicated for the relief of the pain of osteoarthritis of joints responsive to topical treatment; in particular, it was prescribed for the joints in the hands, knees and feet.[56] It has not been shown to work for strains, sprains, bruises or sports injuries.[56] It was intended for the temporary relief of joint pain due to the most common type of arthritis, osteoarthritis.[56] In February 2020, the gel became an over-the-counter drug and the FDA granted the approval of the nonprescription product to GlaxoSmithKline plc.[56]

Formulations and trade names

խմբագրել

The name "diclofenac" derives from its chemical name: 2-(2,6-dichloranilino) phenylacetic acid. Diclofenac was first synthesized by Alfred Sallmann and Rudolf Pfister and introduced as Voltaren by Ciba-Geigy (now Novartis) in 1973, by GlaxoSmithKline.[57]

In the United Kingdom, United States, India, and Brazil diclofenac may be supplied as either the sodium or potassium salt; in China, it is most often supplied as the sodium salt, while in some other countries it is only available as the potassium salt. It is often available without prescription in many of these countries.Կաղապար:Mcn

Pennsaid is a minimally systemic prescription topical lotion formulation of 1.5% w/w diclofenac sodium, which is approved in the US, Canada and other countries for osteoarthritis of the knee.

Flector Patch, a minimally systemic topical patch formulation of diclofenac, is indicated for acute pain due to minor sprains, strains, and contusions. The patch has been approved in many other countries outside the US under different brand names.

Voltaren and Voltarol contain the sodium salt of diclofenac. In the United Kingdom, Voltarol can be supplied with either the sodium salt or the potassium salt, while Cataflam, sold in some other countries, is the potassium salt only. However, Voltarol Emulgel contains diclofenac diethylammonium, in which a 1.16% concentration is equivalent to a 1% concentration of the sodium salt. In 2016 Voltarol was one of the biggest selling branded over-the-counter medications sold in Great Britain, with sales of £39.3 million.[58]

Diclofenac is available in stomach acid-resistant formulations (25 and 50 mg), fast-disintegrating oral formulations (25 and 50 mg), powder for oral solution (50 mg), slow- and controlled-release forms (75, 100 or 150 mg), suppositories (50 and 100 mg), and injectable forms (50 and 75 mg).

Diclofenac is also available over-the-counter in some countries: 12.5 mg diclofenac as potassium salt in Switzerland (Voltaren dolo), the Netherlands (Voltaren K), and preparations containing 25 mg diclofenac as the potassium salt in Germany (various trade names), New Zealand, Australia, Japan, (Voltaren Rapid), and Sweden (Voltaren T and Diclofenac T). Diclofenac as potassium salt can be found throughout the Middle East in 25 mg and 50 mg doses (Cataflam).

Solaraze (3% diclofenac sodium gel) is topically applied, twice a day for three months, to manage the skin condition known as actinic or solar keratosis. Parazone-DP is a combination of diclofenac potassium and paracetamol, manufactured and supplied by Ozone Pharmaceuticals and Chemicals, Gujarat, India. It is sold in Uruguay alone or, in combination with orphenadrine to treat muscle spasms/pain due to injuries (Dicloflex Ion).

On 14 January 2015, diclofenac oral preparations were reclassified as prescription-only medicines in the UK. The topical preparations are still available without prescription.[59]

Diclofenac formulations are available worldwide under many different trade names.[60]

Ecological effects

խմբագրել

Use of diclofenac for animals is controversial due to toxicity when eaten by scavenging birds that eat dead animals; the medication has been banned for veterinary use in many countries.

Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent – a 95% decline by 2003[61] and a 99.9% decline by 2008. The mechanism is presumed to be renal failure;[62] however, toxicity may be due to direct inhibition of uric acid secretion in vultures.[63] Vultures eat the carcasses of livestock that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical,[64] as vultures do not have a particular enzyme to break down diclofenac. At a meeting of the National Wildlife Board in March 2005, the Government of India announced it intended to phase out the veterinary use of diclofenac.[65] Meloxicam is a safer alternative to replace use of diclofenac.[66] It is more expensive than diclofenac, but the cost is droppingԿաղապար:When as more pharmaceutical companies are beginning to manufacture it.

Steppe eagles have the same vulnerability to diclofenac as vultures and may also fall victim to it.[67] Diclofenac has been shown also to harm freshwater fish species such as rainbow trout.[68][69][70][71] In contrast, New World vultures, such as the turkey vulture, can tolerate at least 100 times the level of diclofenac that is lethal to Gyps species.[72]

"The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian Subcontinent that pose a potential threat to human health. In many places, populations of feral dogs (Canis familiaris) have increased sharply from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses. Associated with the rise in dog numbers is an increased risk of rabies"[66] and casualties of almost 50,000 people.[73] The Government of India cites this as one of the major consequences of a vulture species extinction.[65] A major shift in the transfer of corpse pathogens from vultures to feral dogs and rats could lead to a disease pandemic, causing millions of deaths in a crowded country like India, whereas vultures' digestive systems safely destroy many species of such pathogens. Vultures are long-lived and slow to breed. They start breeding only at the age of six and only 50% of young survive. Even if the government ban is fully implemented, it will take several years to revive the vulture population.[74]

The loss of vultures has had a social impact on the Indian Zoroastrian Parsi community, who traditionally use vultures to dispose of human corpses in Towers of Silence, but are now compelled to seek alternative methods of disposal.[66]

Despite the vulture crisis, diclofenac remains available in other countries including many in Europe.[75] It was controversially approved for veterinary use in Spain in 2013 and continues to be available, despite Spain being home to around 90% of the European vulture population and an independent simulation showing that the drug could reduce the population of vultures by 1-8% annually. Spain's medicine agency presented simulations suggesting that the number of deaths would be quite small.[76][77]


References

խմբագրել
  1. ↑ «Von Willebrand disease: MedlinePlus Medical Encyclopedia». www.nlm.nih.gov. Վերցված է 2016-06-26-ին.
  2. ↑ Goodeve A, James P (1993). «von Willebrand Disease». PMID 20301765. {{cite journal}}: Cite journal requires |journal= (օգնություն)
  3. ↑ Swystun LL, James PD (January 2017). «Genetic diagnosis in hemophilia and von Willebrand disease». Blood Reviews. 31 (1): 47–56. doi:10.1016/j.blre.2016.08.003. PMID 27596108.
  4. ↑ Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel TL, Rick ME, Sadler JE, Weinstein M, Yawn BP (March 2008). «von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA)». Haemophilia. 14 (2): 171–232. doi:10.1111/j.1365-2516.2007.01643.x. PMID 18315614.
  5. ↑ Lavin M, Aguila S, Schneppenheim S, Dalton N, Jones KL, O'Sullivan JM, O'Connell NM, Ryan K, White B, Byrne M, Rafferty M, Doyle MM, Nolan M, Preston RJ, Budde U, James P, Di Paola J, O'Donnell JS (November 2017). «Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels». Blood. 130 (21): 2344–2353. doi:10.1182/blood-2017-05-786699. PMC 5881608. PMID 28916584.
  6. ↑ «Von Willebrand Disease». hemophilia.org. 4 March 2014. Վերցված է 4 April 2018-ին.
  7. ↑ Lavin M, Aguila S, Dalton N, Nolan M, Byrne M, Ryan K, White B, O'Connell NM, O'Sullivan JM, Di Paola J, James PD, O'Donnell JS (July 2018). «Significant gynecological bleeding in women with low von Willebrand factor levels». Blood Advances. 2 (14): 1784–1791. doi:10.1182/bloodadvances.2018017418. PMC 6058240. PMID 30042144.
  8. ↑ De Wee EM, Knol HM, Mauser-Bunschoten EP, van der Bom JG, Eikenboom JC, Fijnvandraat K, De Goede-Bolder A, Laros-van Gorkom B, Ypma PF, Zweegman S, Meijer K, Leebeek FW (November 2011). «Gynaecological and obstetric bleeding in moderate and severe von Willebrand disease» (PDF). Thrombosis and Haemostasis. 106 (5): 885–92. doi:10.1160/TH11-03-0180. PMID 21947221.
  9. ↑ 9,0 9,1 9,2 National Hemophilia Federation (2014-03-05). «Von Willebrand Disease». National Hemophilia Federation. Վերցված է 3 December 2017-ին.
  10. ↑ James PD, Notley C, Hegadorn C, Leggo J, Tuttle A, Tinlin S, Brown C, Andrews C, Labelle A, Chirinian Y, O'Brien L, Othman M, Rivard G, Rapson D, Hough C, Lillicrap D (January 2007). «The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian cohort study». Blood. 109 (1): 145–54. doi:10.1182/blood-2006-05-021105. PMID 17190853.
  11. ↑ Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR (June 1987). «The effect of ABO blood group on the diagnosis of von Willebrand disease». Blood. 69 (6): 1691–5. doi:10.1182/blood.V69.6.1691.1691. PMID 3495304.
  12. ↑ Swami A, Kaur V (November 2017). «von Willebrand Disease: A Concise Review and Update for the Practicing Physician». Clinical and Applied Thrombosis/Hemostasis. 23 (8): 900–910. doi:10.1177/1076029616675969. PMID 27920237.
  13. ↑ Christine A. Lee, Rezan A. Kadir, Peter A. Kouides: Inherited Bleeding Disorders in Women P., 1-4051-6915-X
  14. ↑ Favaloro EJ, Bonar R, Kershaw G, Sioufi J, Baker R, Hertzberg M, Street A, Marsden K (July 2006). «Reducing errors in identification of von Willebrand disease: the experience of the royal college of pathologists of australasia quality assurance program». Seminars in Thrombosis and Hemostasis. 32 (5): 505–13. doi:10.1055/s-2006-947865. PMID 16862524.
  15. ↑ Chandler WL, Peerschke EI, Castellone DD, Meijer P (June 2011). «Von Willebrand factor assay proficiency testing. The North American Specialized Coagulation Laboratory Association experience». American Journal of Clinical Pathology. 135 (6): 862–9. doi:10.1309/AJCPH5JK4ONENPAE. PMID 21571959.
  16. ↑ Sadler JE (April 1994). «A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis». Thrombosis and Haemostasis. 71 (4): 520–5. doi:10.1055/s-0038-1642471. PMID 8052974.
  17. ↑ Oxford Handbook of Clinical Haematology, Chapter 11
  18. ↑ Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, Bauters A, Decoene C, Goudemand J, Prat A, Jude B (July 2003). «Acquired von Willebrand syndrome in aortic stenosis». The New England Journal of Medicine. 349 (4): 343–9. doi:10.1056/NEJMoa022831. PMID 12878741.
  19. ↑ Uriel N, Pak SW, Jorde UP, Jude B, Susen S, Vincentelli A, Ennezat PV, Cappleman S, Naka Y, Mancini D (October 2010). «Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation». Journal of the American College of Cardiology. 56 (15): 1207–13. doi:10.1016/j.jacc.2010.05.016. PMID 20598466.
  20. ↑ 20,0 20,1 20,2 20,3 20,4 20,5 20,6 20,7 20,8 «Diclofenac epolamine Monograph for Professionals». Drugs.com (անգլերեն). AHFS. Վերցված է 22 December 2018-ին.
  21. ↑ Chung, CH (11 December 2017). «The use of Injectable Nonsteroidal Anti-Inflammatory Drugs in Local Accident & Emergency Practice». Hong Kong Journal of Emergency Medicine. 9 (2): 65–71. doi:10.1177/102490790200900201.
  22. ↑ 22,0 22,1 22,2 22,3 British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. էջեր 1033–1035. ISBN 978-0857112989.
  23. ↑ Mosby's Drug Reference for Health Professions (անգլերեն). Elsevier Health Sciences. 2017. էջ 398. ISBN 9780323566827.
  24. ↑ Fischer, Janos (2006). Analogue-based drug discovery. Wiley-VCH. էջ 517. ISBN 978-3527312573.
  25. ↑ «Diclofenac Sodium». International Medical Products Price Guide. Վերցված է 4 December 2019-ին.(չաշխատող հղում)
  26. ↑ «NADAC as of 2018-12-19». Centers for Medicare and Medicaid Services (անգլերեն). Վերցված է 22 December 2018-ին.
  27. ↑ «The Top 300 of 2020». ClinCalc. Վերցված է 11 April 2020-ին.
  28. ↑ «Diclofenac - Drug Usage Statistics». ClinCalc. Վերցված է 11 April 2020-ին.
  29. ↑ «Diclofenac Epolamine». The American Society of Health-System Pharmacists. Վերցված է 3 April 2011-ին.
  30. ↑ 30,0 30,1 «RUFENAL». Birzeit Pharmaceutical Company. Արխիվացված է օրիգինալից 2011-05-26-ին.
  31. ↑ «Patient Site - CAMBIA (diclofenac potassium) for oral solution». cambiarx.
  32. ↑ Dutta NK, Mazumdar K, Dastidar SG, Park JH (October 2007). «Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice». International Journal of Antimicrobial Agents. 30 (4): 336–40. doi:10.1016/j.ijantimicag.2007.04.016. PMID 17644321.
  33. ↑ «Diclofenac (Topical Application Route) Description and Brand Names - Mayo Clinic». www.mayoclinic.com.
  34. ↑ cbg-meb.nl, SPC Netherlands
  35. ↑ Wakai A, Lawrenson JG, Lawrenson AL, Wang Y, Brown MD, Quirke M, և այլք: (May 2017). «Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions». The Cochrane Database of Systematic Reviews. 5: CD009781. doi:10.1002/14651858.CD009781.pub2. PMC 6481688. PMID 28516471.
  36. ↑ «WHO - WHO's cancer pain ladder for adults». www.who.int.
  37. ↑ «Diclofenac Potassium». Drugs.com. Drugsite Trust. Վերցված է 2015-11-15-ին.
  38. ↑ 38,0 38,1 38,2 38,3 38,4 38,5 38,6 38,7 Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, և այլք: (August 2013). «Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials». Lancet. 382 (9894): 769–79. doi:10.1016/S0140-6736(13)60900-9. PMC 3778977. PMID 23726390.
  39. ↑ Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (June 2006). «Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials». BMJ. 332 (7553): 1302–8. doi:10.1136/bmj.332.7553.1302. PMC 1473048. PMID 16740558.
  40. ↑ «Heart risk warning over painkiller». BBC News. 29 June 2013 – via www.bbc.co.uk.
  41. ↑ «Press release: Diclofenac tablets now only available as a prescription medicine». Medicines and Healthcare Products Regulatory Agency. January 14, 2015. Վերցված է January 14, 2015-ին.
  42. ↑ Solomon DH, Avorn J, Stürmer T, Glynn RJ, Mogun H, Schneeweiss S (May 2006). «Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk». Arthritis and Rheumatism. 54 (5): 1378–89. doi:10.1002/art.21887. PMID 16645966.
  43. ↑ Fosbøl EL, Folke F, Jacobsen S, Rasmussen JN, Sørensen R, Schramm TK, և այլք: (July 2010). «Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals». Circulation: Cardiovascular Quality and Outcomes. 3 (4): 395–405. doi:10.1161/CIRCOUTCOMES.109.861104. PMID 20530789.
  44. ↑ FitzGerald GA, Patrono C (August 2001). «The coxibs, selective inhibitors of cyclooxygenase-2». The New England Journal of Medicine. 345 (6): 433–42. doi:10.1056/NEJM200108093450607. PMID 11496855.
  45. ↑ «Voltaren Gel (diclofenac sodium topical gel) 1% - Hepatic Effects Labeling Changes». 2009-12-04. Արխիվացված է օրիգինալից 2015-03-29-ին.
  46. ↑ 46,0 46,1 Brater DC (April 2002). «Renal effects of cyclooxygyenase-2-selective inhibitors». Journal of Pain and Symptom Management. 23 (4 Suppl): S15–20, discussion S21–3. doi:10.1016/S0885-3924(02)00370-6. PMID 11992745.
  47. ↑ Becker, Rachel (2016). «Cattle drug threatens thousands of vultures». Nature. doi:10.1038/nature.2016.19839.
  48. ↑ «Diclofenac Side Effects». Drugs.com. Վերցված է 21 January 2013-ին.
  49. ↑ Dastidar SG, Ganguly K, Chaudhuri K, Chakrabarty AN (April 2000). «The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis». International Journal of Antimicrobial Agents. 14 (3): 249–51. doi:10.1016/S0924-8579(99)00159-4. PMID 10773497.
  50. ↑ Fowler PD, Shadforth MF, Crook PR, John VA (1983). «Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis». European Journal of Clinical Pharmacology. 25 (3): 389–94. doi:10.1007/BF01037953. PMID 6628528.
  51. ↑ Scholer DW, Ku EC, Boettcher I, Schweizer A (April 1986). «Pharmacology of diclofenac sodium». The American Journal of Medicine. 80 (4B): 34–8. doi:10.1016/0002-9343(86)90077-x. PMID 3085490.
  52. ↑ Cryer B, Feldman M (May 1998). «Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs». The American Journal of Medicine. 104 (5): 413–21. doi:10.1016/S0002-9343(98)00091-6. PMID 9626023.
  53. ↑ Voilley N, de Weille J, Mamet J, Lazdunski M: Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001 Oct 15;21(20):8026-33.
  54. ↑ «NADAC as of 2018-12-19». Centers for Medicare and Medicaid Services. Վերցված է 22 December 2018-ին.
  55. ↑ Tarascon Pocket Pharmacopoeia 2019 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. 2018. էջ 6. ISBN 978-1-284-16754-2.
  56. ↑ 56,0 56,1 56,2 56,3 Քաղվածելու սխալ՝ Սխալ <ref> պիտակ՝ «FDA switch» անվանումով ref-երը տեքստ չեն պարունակում:
  57. ↑ Altman R, Bosch B, Brune K, Patrignani P, Young C (May 2015). «Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology». Drugs. 75 (8): 859–77. doi:10.1007/s40265-015-0392-z. PMC 4445819. PMID 25963327.
  58. ↑ «A breakdown of the over-the-counter medicines market in Britain in 2016». Pharmaceutical Journal. 28 April 2017. Վերցված է 29 May 2017-ին.
  59. ↑ «Oral diclofenac presentations with legal status 'P' – reclassified to POM - GOV.UK». www.gov.uk.
  60. ↑ «Diclofenac». Drugs.com. Վերցված է 22 December 2018-ին.
  61. ↑ Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, և այլք: (February 2004). «Diclofenac residues as the cause of vulture population decline in Pakistan». Nature. 427 (6975): 630–3. Bibcode:2004Natur.427..630O. doi:10.1038/nature02317. PMID 14745453.
  62. ↑ Swan GE, Cuthbert R, Quevedo M, Green RE, Pain DJ, Bartels P, և այլք: (June 2006). «Toxicity of diclofenac to Gyps vultures». Biology Letters. 2 (2): 279–82. doi:10.1098/rsbl.2005.0425. PMC 1618889. PMID 17148382.
  63. ↑ Naidoo V, Swan GE (April 2009). «Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction» (PDF). Comparative Biochemistry and Physiology. Toxicology & Pharmacology. 149 (3): 269–74. doi:10.1016/j.cbpc.2008.07.014. hdl:2263/13907. PMID 18727958.
  64. ↑ «Vet drug 'killing Asian vultures'». BBC News. 2004-02-28.
  65. ↑ 65,0 65,1 «Saving the Vultures from Extinction» (Press release). Press Information Bureau, Government of India. 2005-05-16. Վերցված է 2006-05-12-ին.
  66. ↑ 66,0 66,1 66,2 Swan G, Naidoo V, Cuthbert R, Green RE, Pain DJ, Swarup D, և այլք: (March 2006). «Removing the threat of diclofenac to critically endangered Asian vultures». PLOS Biology. 4 (3): e66. doi:10.1371/journal.pbio.0040066. PMC 1351921. PMID 16435886.{{cite journal}}: CS1 սպաս․ չպիտակված ազատ DOI (link)
  67. ↑ Phadnis, Mayuri (May 28, 2014). «Eagles fall prey to vulture-killing chemical». Pune Mirror. Վերցված է May 28, 2014-ին.
  68. ↑ Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (June 2004). «Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I: histopathological alterations and bioaccumulation in rainbow trout». Aquatic Toxicology. 68 (2): 141–50. doi:10.1016/j.aquatox.2004.03.014. PMID 15145224.
  69. ↑ Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler HR, Schwaiger J (June 2004). «Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part II: cytological effects in liver, kidney, gills and intestine of rainbow trout (Oncorhynchus mykiss)». Aquatic Toxicology. 68 (2): 151–66. doi:10.1016/j.aquatox.2004.03.015. PMID 15145225.
  70. ↑ Schwaiger & Triebskorn (2005). UBA-Berichte 29/05: 217-226.
  71. ↑ Triebskorn R, Casper H, Scheil V, Schwaiger J (February 2007). «Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio)». Analytical and Bioanalytical Chemistry. 387 (4): 1405–16. doi:10.1007/s00216-006-1033-x. PMID 17216161.
  72. ↑ Rattner BA, Whitehead MA, Gasper G, Meteyer CU, Link WA, Taggart MA, և այլք: (November 2008). «Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac». Environmental Toxicology and Chemistry. 27 (11): 2341–5. doi:10.1897/08-123.1. PMID 18476752.
  73. ↑ Walker, Matt (August 6, 2008). «Rabies tragedy follows loss of India's vultures». New Scientist.
  74. ↑ Choudhary, Srishti (August 29, 2016). «'Decline in vulture population has given rise to diseases': Dr Vibhu Prakash». The Indian Express. Վերցված է December 12, 2018-ին.
  75. ↑ «E-010588/2015: answer given by Mr Andriukaitis on behalf of the Commission». European Parliament. Վերցված է 2 May 2016-ին.
  76. ↑ Becker, Rachel (2016). «Cattle drug threatens thousands of vultures». Nature. doi:10.1038/nature.2016.19839. Վերցված է 2 May 2016-ին. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (օգնություն)
  77. ↑ International, BirdLife. «Vulture killing drug now available on EU market». www.birdlife.org.
խմբագրել

Դիաբետիկ ռետինոպաթիա

խմբագրել

Հետազոտություն

խմբագրել

Light treatment

խմբագրել

A medical device comprising a mask that delivers green light through the eyelids while a person sleeps was under development in 2016.[1][2] The light from the mask stops rod cells in the retina from dark adapting, which is thought to reduce their oxygen requirement, which in turn diminishes new blood vessel formation and thus prevents diabetic retinopathy.[1] As of 2016 a large clinical trial was underway.[1] As of 2018, the results from the clinical trial showed no long-term therapeutic benefit from using the mask in diabetic retinopathy patients.

C-սպիտակուց

խմբագրել

C-peptide had shown promising results in treatment of diabetic complications incidental to vascular degeneration.[3] Creative Peptides,[4] Eli Lilly,[5] and Cebix[6] all had drug development programs for a C-peptide product. Cebix had the only ongoing program until it completed a Phase IIb trial in December 2014 that showed no difference between C-peptide and placebo, and it terminated its program and went out of business.[7][8]

Ցողունաբջջային թերապիա

խմբագրել

Clinical trials are under way or are being populated in preparation for study at medical centers in Brazil, Iran and the United States. Current trials involve using the patients' own stem cells derived from bone marrow and injected into the degenerated areas in an effort to regenerate the vascular system.[9]

Զարկերակային ճնշման կարգավորում

խմբագրել

A Cochrane review examined 15 randomized controlled trials to determine whether interventions that sought to control or reduce blood pressure in diabetics had any effects of diabetic retinopathy.[10] While the results showed that interventions to control or reduce blood pressure prevented diabetic retinopathy for up to 4–5 years in diabetics, there was no evidence of any effect of these interventions on progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs.[10]

Fundoscopic image analyses

խմբագրել

Diabetic retinopathy is diagnosed entirely by recognizing abnormalities on retinal images taken by fundoscopy. Color fundus photography is mainly used for staging the disease. Fluorescein angiography is used to assess the extent of retinopathy that aids in treatment plan development. Optical coherence tomography (OCT) is used to determine the severity of edema and treatment response.[11]

Because fundoscopic images are the main sources for diagnosis of diabetic retinopathy, manually analyzing those images can be time-consuming and unreliable, as the ability of detecting abnormalities varies by years of experience.[12] Therefore, scientists have explored developing computer-aided diagnosis approaches to automate the process, which involves extracting information about the blood vessels and any abnormal patterns from the rest of the fundoscopic image and analyzing them.[13]

Ծանոթագրություններ

խմբագրել
  1. ↑ 1,0 1,1 1,2 Sivaprasad S, Arden G (February 2016). «Spare the rods and spoil the retina: revisited». Eye. 30 (2): 189–92. doi:10.1038/eye.2015.254. PMC 4763134. PMID 26656085.
  2. ↑ «Noctura 400 Sleep Mask for diabetic retinopathy ‐ Horizon Scanning Research & Intelligence Centre». www.hsric.nihr.ac.uk. Արխիվացված է օրիգինալից 2015-09-25-ին. Վերցված է 2015-09-24-ին.
  3. ↑ Bhatt MP, Lim YC, Ha KS (November 2014). «C-peptide replacement therapy as an emerging strategy for preventing diabetic vasculopathy». Cardiovascular Research. 104 (2): 234–44. doi:10.1093/cvr/cvu211. PMID 25239825.
  4. ↑ «C-peptide - Creative Peptides -». AdisInsight. Վերցված է 22 October 2016-ին.
  5. ↑ «C-peptide – Eli Lilly». AdisInsight. Վերցված է 22 October 2016-ին.
  6. ↑ «C-peptide long-acting – Cebix». adisinsight.springer.com. AdisInsight. Վերցված է 22 October 2016-ին.
  7. ↑ Bigelow, Bruce V. (23 February 2015). «Cebix Shuts Down Following Mid-Stage Trial of C-Peptide Drug». Xconomy. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (օգնություն)
  8. ↑ Garde, Damian (February 24, 2015). «Cebix hangs it up after raising $50M for diabetes drug». FierceBiotech. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (օգնություն)
  9. ↑ Ljubimov, Alexander. «Stem Cell Therapy for Diabetic Retinopathy» (PDF). Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA, USA Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Արխիվացված է օրիգինալից (PDF) 2014-12-30-ին. Վերցված է 2014-12-30-ին. {{cite web}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (օգնություն)
  10. ↑ 10,0 10,1 Do DV, Wang X, Vedula SS, Marrone M, Sleilati G, Hawkins BS, Frank RN (January 2015). «Blood pressure control for diabetic retinopathy». The Cochrane Database of Systematic Reviews. 1: CD006127. doi:10.1002/14651858.CD006127.pub2. PMC 4439213. PMID 25637717.
  11. ↑ «Diabetic Retinopathy». Merck Manuals Professional Edition. Վերցված է 2016-11-13-ին.
  12. ↑ Kaur M, Talwar R (2014). «Review on: Blood Vessel Extraction and Eye Retinopathy Detection». International Journal of Computer Science and Information Technologies. 5 (6): 7513–7516.
  13. ↑ Ahmad A, Mansoor AB, Mumtaz R, Khan M, Mirza SH (2014-12-01). «Image processing and classification in diabetic retinopathy: A review». 2014 5th European Workshop on Visual Information Processing (EUVIP): 1–6. doi:10.1109/EUVIP.2014.7018362. ISBN 978-1-4799-4572-6.
Ստացված է «https://hy.wikipedia.org/w/index.php?title=Մասնակից:Տաթև_Հարությունյան/Ավազարկղ&oldid=8435153» էջից