Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above.
During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach.
Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis.
So, summarizing, in the evaluation of a case of thrombocytopenia, all the
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above.
During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach.
Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis.
So, summarizing, in the evaluation of a case of thrombocytopenia, all the
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
Jorge E. Cortes, MD discusses leukemia in this CME activity titled Faster, Better, Safer—Getting CML Treatment Right: How to Enhance Outcomes With Precision Medicine in the TKI Era. For the full presentation, downloadable practice aids, transcript, complete CME information, and to apply for credit please visit us at http://bit.ly/2gXAedd. CME credit will be available until December 12, 2017.
detailed discussion on cytogenetics in CML - Pathophysiology, treatment, TKI Resistance, Mutation analysis timing, various mutations in CML, BCR-ABL1 Variants, Significance of mutations and management.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
2. 28 yr male patient came with c/o
abdominal pain-1 week in duration
involving predominantly
the left upper and
centre of the abdomen
vague dragging pain
assoc with fullness of abd
no h/o any aggravating or
relieving factors
3. h/o early satiety +
h/o loss of appetite +
No h/o loss of weight
No h/o jaundice
No h/o haematemesis
No h/o altered bowel habits
No h/o bleeding tendencies
4. PAST h/o -> No h/o Tb/HTN/DM
PERSONAL h/o -> consumes alcohol
occasionally
not a smoker
5. O/E – Pt conscious
oriented
afebrile
anemic
no Cyanosis,clubbing,icterus,
lymphadenopathy
B.P-110/70 mmHG
P.R -80 min
6. P/A –mild distention of abdomen+
no dialated viens,scars or sinuses
massive spleenomegaly(+) crossing
the umbilicus
no hepatomegaly
no FF+
7. CVS – S1S2(+)
NO murmurs
RS – NVBS+
no added sounds
CNS - NFND
12. CBC
TC – 1,60,000
SHIFT TO LEFT
BLAST 1%
HB – 9.2
PLATLET -1,80,000
Chronic phase of CML
P/S
Markedly increased TC,
showsMYELOBLAST,PR
OMYELOCYTE,METAMY
ELOCYTE,BAND FORMS
13.
14.
15. BONE MARROW FRAGMENT
SHOWING A DENSLLY CELLULAR MARROW
FRAGMENT WITH ABSENT FAT CELLS
16.
17. LOW POWER MICROSCOPE:
MYELOID HYPERPLASIA WITH RELATIVELY
REDUCED ERYTHROID PROGENITORS
18.
19.
20.
21. Patient was started on Imatinib mesylate
400mg 1-0-0
22.
23.
24. CML accounts for 15% of all cases of
leukemia.
More common in men
Peak incidence : fourth and fifth decade
25.
26. In CML the c-ABL gene is translocated from
its normal abode on chromosone 9 to
chromosone 22,where it fuses with bcr gene.
As a consequence of the fusion, c-ABL loses a
region that controls tyrosine kinase activity.
Thus the BCR-ABL protien,the product of the
fusion gene has potent and constitutive
tyrosine kinase activity.
29. EASY FATIGABILITY
DECREASE TOLERANCE TO EXERTION
ABDOMINAL DISCOMFORT AND EARLY
SATIETY( DUE TO SPLENIC ENLARGEMENT)
WIEGHT LOSS AND EXCESSIVE SWEATING
The symptoms are vague, nonspecific and
gradual in onset
30. A physical examination may detect pallor and
splenomegaly.The latter was present in 90%
of patients.
UNCOMMON PRESENTATIONS :
Dramatic hypermetabolism(night sweats,wt
loss,heat intolerance)
Acute gouty arthritis(due to hyperurecemia)
Priapism,tinnitus
Lt upper quadrant n lt shoulder pain due to
splenic infarction and perisplenitis.
31. CML is often suspected on the basis on
the complete blood count, which shows
increased granulocytes of all types, typically
including maturemyeloid cells.
Basophils and eosinophils are almost universally
increased; this feature may help differentiate
CML from a leukemoid reaction.
A bone marrow biopsy is often performed as
part of the evaluation for CML, and CML is
diagnosed by detecting the Philadelphia
chromosome.
32. 10–19% myeloblasts in the blood or bone
marrow.
>20% basophils in the blood or bone marrow
Platelet count <100,000, unrelated to therapy
Cytogenetic evolution with new abnormalities in
addition to the Philadelphia chromosome
Increasing splenomegaly or white blood cell
count, unresponsive to therapy
33. Blast crisis is the final phase in the evolution of CML, and
behaves like an acute leukemia, with rapid progression
and short survival.
Blast crisis is diagnosed if any of the following are present
in a patient with CML:
>20% myeloblasts or lymphoblasts in the blood or bone
marrow.
Large clusters of blasts in the bone marrow on biopsy.
Development of a chloroma (solid focus of leukemia
outside the bone marrow)
34. IMATINIB MESYLATE
STEM CELL TRANSPLANTATION
IFN-ALPHA
HYDROXYUREA
SECOND GENERATION TK INHIBITOR-
DASATINIB AND NILOTINIB
35. IMTINIB NOW IS USED AS INITIAL THERAPY IN
ALMOST ALL PATIENTS WITH CML.
IN CASES WHERE WBC COUNT IS MARKEDLY
ELEVATED HYDROXYUREA CAN BE USED TO
PREVENT HYPERLEUKOCYTIC SYNDROME.
36. The bcr abl oncoprotien
with a molecule of ATP in
d kinase pocket.
Phosphorylation - >
substrate .Activates
downstream molecules
Imatinib occcupies d
kinase pocket preventing
phosphorylation of its
substrates
37.
38. HAEMATOLOGIC
RESPONSE
CYTOGENETIC
RESPONSE
MOLECULAR
RESPONSE(BCR
ABL TO
CONTROL GENE
RATIO
ACCORDING TO
IS SCALE)
FREQUENCY .Every 2 weeks
until a complete
response has been
achieved and
confirmed.
every 3 months
unless othwise
required
every 6 months
until a complete
response has
been achieved
and confirmed.
then every 12
months
EVERY 3
MONTHS
METHOD complete blood
count (CBC) with
differential
Conventional
cytogenetic
examination
.FISH
(fluorescene in
situ
hybridisation)
(only before
treatment)
.RQ-PCR
(Reverse
transcription
quantitative
polymerase
chain reaction)
39. SMENT METHOD
SUBOPTIMAL RESPONSE FAILURE
tologic No Complete hematologic
response(CHR) within 3
months
No hematologic response
within 3 months
Loss of CHR at any time
enetic No MCyR (Major cytogenetic
response )within 6 months
No CCyR(Complete
cytogenetic response) within
18 months
.No cytogenetic response
within 6 months
No MCyR within 12 mont
No CCyR within 18 mont
Loss of CCyR at any time
Not applicable.
CULAR No MMR(Major molecular
response) within 8 months
Loss of MMR at any time
40.
41. Second generation TKI like
DASATINIB
NILOTINIB
Allogenic human stem cell transplant
42. Well tolerated compared to other treatment
options in CML
Superficial edema
Nausea,muscle cramps
Rash,Diarrhea
Uncommon side effects:tumour lysis in
accelerated phase,splenic rupture,cerebral
edema,Varicella Zoster infections
43. Imatinib is not recommended during
pregnancy.
Hydroxyurea has the lowest mutagenic
potential among the cytotoxic agents.
IFN can also be safely used during pregnancy.
44. Patients who are younger than 65 yrs and
who have a identical twin or a
histocompatible sibling can be transplanted
after intensive therapy usually with
cyclophosphamide.
GVHD is common.