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FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINI...Alok Gupta
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINICAL OUTCOME INACUTE LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
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This is an overview of the adjuvant Tx of pancreatic CA. A Lecture that was given in the annual conference of NCI Egypt: 45 years against cancer in Egypt. Cairo, April, 2013
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Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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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
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1. Highlights 11- ICML Lugano 15-18 June 2011 Anastasios Stathis, MD Oncology Institute of Southern Switzerland CH-6500 Bellinzona
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4. Hematological response to antiviral treatment in 94 patients with indolent B-NHL associated with HCV infection: studies of the FIL L. Arcaini et al. Ann Oncol 2011, 22 Suppl 4:iv129 (abs 138) 94 pts with iNHL and HCV infection 36 pts received IFN (in 26 with ribavirin) 57 received peg-IFN (in 53 plus ribavirin) 76 pts treated in 1st line 18 pts had AT in 2nd line CR 47%, PR 30 % in first line Lower response rate in 2nd line Similar responses between IFN and peg-IFN Better long term control of iNHL with peg-IFN PFS 5-yr OS 94%; 5-yr PFS 78% DOR > 3 yrs in 40% of pts
5. PET+ lesions at the end of chemotherapy for Hodgkin Lymphona Engert et al., Abstr. 45, ICML-11 728 advanced HL with residual disease after 6-8 BEACOPP 74% PET - No RT only 5% relapsed (NPV 94.6%) 26% PET + RT Conclusion : PET - residual disease (after BEACOPP) do NOT need RT
6. HD16 R PET scan in low risk HL : The GHSD HD16 trial
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8. DA-EPOCH-R for Burkitt’s lymphoma and PMBCL 30 Burkitt at 5y median FU EFS 97%, OS 100% 40 PMBCL at 4y median FU EFS 95%, OS 100% only 3/40 needed RT/surgery for PET+ Dunleavy et al., Abstr. 71, ICML-11 Dunleavy et al., Abstr. 150, ICML-11
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10. Centrocytic lymphoma -Described by K. Lennert more than 30 year ago -Accepted as a separate entity in the 1990s
11. The hallmark of mantle cell lymphoma is the t(11;14)(q13;q32) Mantle cell lymphoma
12. MCL frequency at the IOSI Diffuse Large B-cell Lymphoma 37% Follicular Lymphoma 20 % CLL/SLL 15 % MALT lymphoma 7% Mantle Cell Lymphoma 6.5 %
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20. 702 FL patients (EBMT + CIBMTR) Sureda et al., Abstr. 037, ICML-11 Half of relapsed FL are rescued by allo BMT Sibling Unrelated 3y PFS 60% 49% P= 0.02 3Y OS 69% 54% P < 0.01
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22. Treatment of limited-stage DLBCL can be effectively tailored using a PET-based approach LH Sehn et al. 11-ICML (Lugano 2011) - Ann Oncol 2011, 22 Suppl 4:iv91 (abs 028) N=134 Majority of limited stage patients will be PET negative after 3 cycles of R-CHOP and have excellent outcome with systemic therapy alone PET positive patients who complete treatment with IFRT have a high rate of distant relapse, and alternative approaches may be necessary OS N=134
23. R-CHOP 14 vs 21 x 8 in elderly (ASH 2009, Abstract 406, Delarue et al, GELA) ICML update: all 600 patients analysed, 2nd interim analysis. (interim analysis – 200/600 pat.) Delarue et al., Abstr. 106, ICML-11 R-CHOP 14 R-CHOP 21 RR 72% 75% 3y EFS 57% 60% 3y OS 70% 73%
24. A randomized multicentre Phase III study for first-line treatment of young patients with high risk (AAIPI 2-3) Diffuse Large B-Cell Lymphoma: Rituximab plus Dose-Dense chemotherapy CHOP14/ MegaCHOP14 with or without intensified HDC and ASCT. Results of DLCL04 FIL Trial Vitolo U et al. 11-ICML (Lugano 2011) - Ann Oncol 2011, 22 Suppl 4:iv106 (abs 072) CR/PR CR/PR Off study R-MegaCHOP14 x 4 R-CHOP14 x 4 R-MAD x 2 + BEAM + ASCT NR RANDOMIZATION R-MegaCHOP14 x 4 R-CHOP14 x 4 R E S T A G I N G 188 Pts 188 Pts R-MegaCHOP14x2 R-CHOP14 x 4 Off study NR *Patients at risk of CNS recurrence (SIE guidelines 2006): IT Mtx 4 or 6 doses
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29. Immunotoxin: brentuximab vedotin SGN-35 = anti CD30 AB + monomethyl auristatin E (anti-microtubule) 58 ALCL relapsed or refractory (50%) 72% ALK negative ORR 86% CR 53% Duration of response (1wk - 1 year), median not reached Shustov et al., Abstr. 125, ICML-11
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32. Further interesting new antibodies Abstracts, 66, 144, 67, 145, 64, 68 Name Target Activity GA101 CD20 indolent + aggressive NHL lucatumumab CD40 FL dacetuzumab CD40 DLBCL KW-0761 CCR4 ATL blinatumomab CD3/CD19 DLBCL + MCL
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35. 12-ICML June 19-22, 2013 12th INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Lugano, Switzerland Deadlines : ABSTRACT SUBMISSION: February 28, 2013 EARLY REGISTRATION: or on before March 15, 2013 LATE REGISTRATION: from March 16, 2013 (up to 3000 attendees) For information and on-line registration: www.lymphcon.ch
Editor's Notes
The aim of this presentation is to summarize the several lines of evidence which demonstrated an etiopathogenic link between bacterial infections and certain types of lymphoma. The best known model is the one of H Pylori and gastric (MALT) lymphoma... The H Pylori and MALT lymphoma story has begun more than 10 years ago and has generated a fascinating model of tumor growth from the background of a chronic inflammation This story is also the example of how improvements in the biologic knowledge can be translated into novel therapeutic strategies.