خير الناس أنفعهم للناس📚

https://youtu.be/NXp0RmCcAB4?feature=shared

مع إعلان الاحتلال الصهيوني إرسال عينة DNA للجثمان الذي يعتقد أنه ليحي السنوار إلى أوروبا للتأكد من مقتله

ما هي الفكرة العامة لتحليل ال DNA أو ما يسمى ببصمة الشخص الوراثية ال
DNA finger printing

ده فيديوا ربع ساعة هنشرح فيه الفكرة البصمة الوراثية
https://youtu.be/kh61KntDtmw?feature=shared

miRNAs:
جائزة نوبل هذا العام في ال microRNAs، اللي حابب يعرف معلومة عنه

https://youtu.be/5NQmgjY32dA
كلمتين مفصلتين عن ال microRNAs

https://www.facebook.com/share/p/vWA9SoE7XD2Chbw4/

https://www.facebook.com/share/p/5RrUPsWcLzYCX7s7/?mibextid=oFDknk

_______

BM:

ال BM هنا مالوش أهمية في التشخيص ولكن بيتعمل للآتي
1_ perform Cytogenetics
2_ asses BM fibrosis
3_ asses transformation into acute leukemia
لو اتعمل هنلاقيه مثل
peripheral blood ➡
Hypercellular and blast less than 10 %

_______

Cytogenetics :

Positive Philadelphia chromosome t(9,22) detected by karyotyping in 95 % of patients of CML, other 5% CML cases with negative Philadelphia chromosome detected by FISH technique or RT-PCR to detect BCR-ABL fusion gene.
يبقي كده أهم شيء هو ان ال
BCR-ABL mutation gene present into 100% of cases of CML , absence of BCR-ABL fusion gene exclude chronic myelogenous leukemia

في كلام جديد بيقول
Rare patients with leucocytosis and splenomegaly have no demonstrable Ph chromosome or BCR–ABL transcripts and are said to be Ph-negative CML, which has fewer treatment options and a worse prognosis !!!!!.


Other Cytogenetics :

Trisomy 8_9_19_21
Isochromosome 17
Double Philadelphia chromosome

_______

Phase of CML :

1_ Chronic phase
2_ accelerated phase
3_ Blast phase
ال chronic phase قلناها
ال blast phase يعني ال blast cells عدت ال 20%
ال accelerated phase لها criteria
1_ Blast cell 10_19%
2_ basophilia more than 20%
3_ persistent leucocytosis more than 10000 or persistent splenomegally unresponding to treatment
4_ persistent thrombocytosis more than 1 millio
n unresponding to treatment
5_ persistent thrombocytopenia less than 100,000 unrelated to treatment
6_ development of new chromosomal abnormalities

_______

Treatment of chronic myelogenous leukemia ( CML) :

1_ interferon Alfa
2_ Hydroxyurea_ Busulfan
3_ Tyrosine kinase inhibitors :
a_ 1st generation ➡ Imatinib
b_ 2nd generation ➡Dasatinib,
Nilotinib,Bosutinib.
c_ 3rd generation ➡ Ponatinib

4_ Omacetaxin ➡ protein synthesis inhibitors, more selective on BCR-ABL

5_ Allogeneic stem cell transplant


Special situation :

Imatinib resistant CML➡use Dasatinib or Nilotinib.
CML with T315I mutation ➡ use ponatinib.


#دمحمد_بهجت_سفيان_medical_biochimestry

Chronic myelogenous leukemia (CML) :
بسم الله الرحمن الرحيم
هتكلم اليوم إن شاء الله عن CML


Definition :

CML is a myeloproliferative neoplasm with an incidence if 1–2 per 100 000 population averaging 700 new cases in the UK each year.

_______

Pathogenesis :

يحدث نتيجة translocation بين
chromosome 9,22
في الذراعين الطويلين للكروموسومين
t(9q,22q)
أشوف الموضوع ده بال karyotyping أصبغ وأشوف التغيير في الكروموسوم تحت الميكروسكوب وده موجود في
95% of CML cases
ال 5% الباقيين من CML إذا لم يوجد في karyotyping علي مستوي الكروموسوم أشوفه علي مستوي ال molecular يعني ايه هو الجين مثلا CGATGAC مثلا يقوم يحصل ال translocation يقوم يجيله sequence جديد ولنفترض CCTAA يبقي الجين الجديد افتراضا مثلا
CGATGACCCTAA
الاتنين علي بعض أعطوا جين آخر حصل transcription وطلع mRNA مختلف طلع لل ribosome في cytoplasm واترجم لبروتين جديد اسمه
p210BCR-ABL protein
البروتين ده له
tyrosine kinase action
يعني بيعمل
activation to specific protein by phosphorylate it's tyrosine residue these proteins activate signal transduction inside the cells leads to activation of replication and cell cycle leads to malignancy ( CML).

يعن عاوز أقول
إنه حصل translocation بين كروموسومات 9_22
نتج عن ذلك جين جديد إسمه BCR _ABL جين.. خرج نتيجة لذلك بروتين جديد اسمه
p210 BCR_ABL protein
ده له tyrosine kinase كتير فيزود
cell cycle
جامد فبيعمل السرطان.

فأنا ممكن أشوف هذه translocation بحاجتين
1_ cytogenetics ➡Philadelphia chromosome by karyotyping or FISH.
2_ molecular genetics ➡ BCR _ABL gene mutation by RTPCR.
ممكن أشوف الكلام ده بال
FISH technique
عن طريق إني أحضر probe لل sequence بتاع
BCR-ABL gene
وأشوفها بالميكروسكوب عن طريق fluorescent
وممكن أشوفها بال RT-PCR

By the time that the disease is diagnosed the bone marrow is grossly hypercellular and there is a marked leucocytosis in the peripheral blood, often with a basophilia, There is also usually an associated anaemia and thrombocytosis, which may be marked, Infiltration of the spleen results in splenomegaly in 50–60% of cases .

_______

Clinical pictures :

بداية المرض ده هييجي بأعراض إيه
40% of patient is asymptomatic
Approximately 30–50% of patients are asymptomatic at diagnosis and are diagnosed by routine physical examination or blood tests done for a different reason.

الباقي بيشتكي من حاجات nonspecific زي
Malaise, easy fatigue, headache,Anorexia,..
الحاجة الوحيدة اللي ممكن تبقي باينه هي
splenomegally even huge splenomegally.

#يبقي المرض ده مهم لأطباء ال
clinical pathology
لأن التشخيص معتمد عليهم بنسبة كبيرة لأن المريض غالبا بيبقي جاي يعمل check up ويفاجأ بالمرض



Age and sex :

Presentation may be at any age, but it is very rare in children, and peaks between the ages of 50 and 70 years, with a slight male predominance.

_______

Investigations :

أول حاجة بنشوفها في صورة الدم نلاقي
Leucocytosis ➡from 12,000 up to1 million

أكثر حاجة تشوف فيها عد أبيض عالي جدا هي
CML and
chronic Prolymphocytic leukaemia

تفرد فيلم تلاقي
Marked shift to the left (stab,band,juvenile, myelocyte,promyelocyte,blast cell)
وان شاء نحط لكل واحدة صورة
في الغالب بنلاقي أكثر حاجة ال
myelocyte and stab.

ال blast cells في الغالب من 1_5% وممكن يوصلوا ل 10% لو زادوا عن 10 يعني من 10_20% تبقي الحالة
accelerated type
لو زاد عن 20% يبقي كده الحالة اتقلبت
acute on top of chronic.

بنبص بنلاقي في الفيلم
Absolute basophilia and eosinophilia
طبعا المهم أكثر ال basophilia وبيهمنا العدد علشان لو زاد عن 20% يبقي accelerated type

بنلاقي في الغالب
Normocytic normochromic anaemia
بسبب ال BM affection
ممكن ال folic acid يستهلك ويقل ويحصل
Macrocytosis and hypersegmented neutrophils.
الصفائح
Usually thrombocytosis and may be normal platelet and may be thrombocytopenia if BM affection occurs

طبعا فيه
Splenomegaly in about 60% of cases.

ممكن بنلاقي أيضا
Other investigations
1_ High LDH and ESR
2_ High uric acid
3_ granulocyte increase synthesis of transcobalamine II ➡ ⬆VIT B12
4_ psudohyperkalemia
5_ NAP score low ( diffentiate between leukaemia and leukemoid reaction)

من فترة كده لقيت ناس كثير بتمدح في الشيعة الروافض، فأصبت بالحزن لضياع أصول العقيدة، وعكفت على الكتب حتى خرجت بهذا الفيديوا
القول الفصل في العقيدة في الصحابة :
https://youtu.be/RNmpUaVBxpE

واليوم لقيت الناس بتمدح تاني الشيعة الروافض، اللي بس عاوز يعرف طوامهم يشوف من الدقيقة 46

CALPROTECTIN

PURPOSE
- Evaluation of patients suspected of having a GIT inflammatory process

- Distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS), when used in conjunction with other diagnostic modalities, including endoscopy, histology, and imaging

Clinical information:
- Calprotectin is expressed primarily by granulocytes and, to a lesser degree, by monocytes/macrophages and epithelial cells.

- In neutrophils, calprotectin comprises almost 60% of the total cytoplasmic protein content.

- Activation of the intestinal immune system leads to recruitment of cells from the innate immune system, including neutrophils >>> The neutrophils are then activated >>> which leads to release of cellular proteins, including calprotectin.
Calprotectin eventually translocates across the epithelial barrier and enters the lumen of the gut.

- As the inflammatory process progresses, the released calprotectin is absorbed by the fecal material before it is excreted from the body.

- The amount of calprotectin present in the feces is proportional to the number of neutrophils within the GIT mucosa and can be used as an indirect marker of intestinal inflammation.

_ Patients with IBD may be diagnosed with Crohn disease or ulcerative colitis.
When used for this differential diagnosis, fecal calprotectin has sensitivity and specificity both of approximately 85%. However, it must be remembered that increases in fecal calprotectin are not diagnostic for IBD, as other disorders such as celiac disease, colorectal cancer, and GIT infections, may also be associated with neutrophilic inflammation.

REFERENCE VALUES
< or =50.0 ug/g (Normal)
50.1-120.0 ug/g (Borderline)
> or =120.1 ug/g (Abnormal)

Reference values apply to all ages.

Interpretattion:
- Calprotectin concentrations of 50.0 ug/g and lower are not suggestive of an active inflammatory process within the GIT. For patients experiencing GIT symptoms, consider further evaluation for functional GIT disorders.

- Calprotectin concentrations between 50.1 and 120.0 ug/g are borderline and may represent a mild inflammatory process, such as in treated IBD or associated with NSAID or aspirin usage. For patients with clinical symptoms suggestive of IBD, retesting in 4 to 6 weeks may be indicated.

- Calprotectin concentrations of 120.1 ug/g and higher are suggestive of an active inflammatory process within the GIT. Further diagnostic testing to determine the etiology of the inflammation is suggested.

Causions:
- Elevations in fecal calprotectin are not diagnostic for IBD, and normal fecal calprotectin concentrations do not exclude the possibility of IBD. Diagnosis of IBD should be based on clinical evaluation, endoscopy, histology, and imaging studies.

- Borderline results in fecal calprotectin may be observed in patients taking NSAIDs, aspirin, or proton-pump inhibitors.

- For borderline results, repeat testing in 4 to 6 weeks is suggested.

- Elevations in fecal calprotectin may be observed in other disease states associated with neutrophilic inflammation of the GIT, including celiac disease, colorectal cancer, and GIT infections.

- Falsely decreased concentrations of fecal calprotectin may be observed in patients with neutropenia or granulocytopenia.

#دمحمد_بهجت_سفيان_medical_biochimestry