2. Circinate Balanitis.
3. Erythema Nodosum
Thursday, January 29, 2009
Skin Manifestations of Reiter's Syndrome
2. Circinate Balanitis.
3. Erythema Nodosum
Tuesday, January 27, 2009
The Most common cause of Allergic Contact Dermatitis in India
The Most common cause of Allergic Contact Dermatitis in India is
'The Congress Grass Plant'
'The Congress Grass Plant'
(Parthenium hysterophorus) - Scientific name, commonly asked.
Monday, January 26, 2009
Components of Horner's Syndrome
1. Miosis
2. Anhidrosis (/ Facial Hypohydrosis)
3. Ptosis
4. Loss of Ciliospinal Reflex
5. Enophthalmos.
* Note : The 17th Edition Harrison mentions only about the first three 'MAP'.
Important Indian Penal Code Sections asked for various Entrance examinations
FORENSIC MEDICINE : IMPORTANT IPC SECTIONS
Sec 31 IPC - Testamentary Capability / Ability to make a will
Sec 84 IPC - Similar to McNaughten's Rule / Criminal Responsibility of an insane
Sec 85 IPC - Crime caused by a person who was intoxicated against will / unknowingly.
Sec 86 IPC - Voluntary Intoxication leading to crime - punishable
Sec 299 IPC - Definition of Culpable Homicide
Sec 300 IPC - Defines Murder
Sec 302 IPC - Punishment of Murder
Sec 304 IPC - Punishment of Culpable Homicide
Sec 304A IPC - Criminal Negligence
Sec 304B IPC - Dowry Death
Sec 320 IPC - Definition of Grievous Hurt
Sec 375 IPC - Definition of Rape
Sec 376 IPC - Punishment of Rape
Sunday, January 25, 2009
Live Attenuated Vaccines
1. MMR
2. BCG
3. Polio
4. Epidemic Typhus
5. Chicken Pox -----------> You can Remember the last 6 as PEt-CITY.
6. Influenza
7. Typhoral
8. Yellow fever Vaccine
Dhanesh V
Thursday, January 22, 2009
What is Nitisinone?
Used for treatment of
1. Hereditary Tyrosinemia Type 1 (HT-1)
2. Alkaptonuria ( Less useful)
Hereditary tyrosinemia type 1 occurs due to a deficiency in fumarylacetoacetase (FAH), the
final enzyme in the tyrosine catabolic pathway.
Mechanism of Action of Nitisinone
Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme
upstream of FAH in the tyrosine catabolic pathway . By inhibiting the normal
catabolism of tyrosine in patients with HT-1, nitisinone prevents the accumulation of the
catabolic intermediates maleylacetoacetate and fumarylacetoacetate. In patients with HT-1,
these catabolic intermediates are converted to the toxic metabolites succinylacetone and
succinylacetoacetate, which are responsible for the observed liver and kidney toxicity.
Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation
of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1.
Since nitisinone inhibits catabolism of tyrosine, use of this drug can result in elevated
plasma levels of this amino acid. Treatment with nitisinone, therefore, requires
restriction of the dietary intake of tyrosine and phenylalanine to prevent the toxicity
associated with elevated plasma levels of tyrosine
Link : More information of Nitisinone at FDA page
Wednesday, January 21, 2009
CATCH 22 - DiGeorge Syndrome / Velo-cardio-facial syndrome
C - Cardiac defects *
A - Abnormal Facies
T - Thymic (and parathyroid) hypoplasia
C - Cleft Palate
H - Hypocalcemia due to parathyroid hypoplasia
22 - It's the most common microdeletion syndrome and it affects Chr.22q11**
Further :
* " In a series of 545 patients with 22q11 deletions, 20% had no cardiac defects (ie, based on clinical examination and echocardiography findings). The most common cardiac anomalies included tetralogy of Fallot (17%), ventricular septal defect and interrupted aortic arch (14% each), pulmonary atresia/ventricular septal defect (10%), and truncus arteriosus (9%). Other anomalies included pulmonic stenosis, atrial septal defect, atrioventricular septal defect, and transposition of great arteries".
http://emedicine.medscape.com/article/135711-overview
** "DiGeorge anomaly is the most frequent contiguous gene deletion syndrome in humans. Microdeletion of chromosome 22 accounts for more than 90% of cases of DiGeorge anomaly. Deletions of chromosome 22q11.2 are found in the vast majority of patients with DiGeorge anomaly and VCFS."
Hope it's of some help.
Tuesday, January 20, 2009
Common Strains of organisms used for Vaccine Production
----------------------------------------------------------------------------------
Measles - Edmonston Zogreb Strain
Typh-Oral - Ty21a Strain
Chicken Pox - OKA Strain
Rabies - Pitts Moore Strain
BCG - Danish 1331
Polio - Lancing, Leon, Brunhilde Strain
Mumps- Jeryll Lynn Strain
Yellow Fever- 17 D vaccine Strain
Hep A - HM175/GBM strain
Rubella- RA 27/3 Strain
Diphtheria- Park Williams 8 Strain
(Note : The BOLD ones are the commonly asked ones in varous PGMEE exams)
--------------------------------------------------------------------------------------------------
Thursday, January 15, 2009
A Few Biochemistry points to start with..
Bioenergetics: Role of ATP
1. First law of thermodynamics states that the total energy of a system, including its surroundings, remains constant. It implies that within the total system, energy is neither lost nor gained during any change. The second law of thermodynamics states that the total entropy of a system must increase if a process is to occur spontaneously.
2. ATP contains 3 phosphate groups, adenine and ribose, Mg2+
3. E.g. of high energy phosphates:
1. Acetyl-Co-A, 2. SAM 3. PRPP 4. UDPglc, 5. PEP 6.Creatine phosphate, 6.1, 3-BPG.
4. ATP à ADP DG0= -7.3kcal/mol or -30.5kJ/mol.
5. ATP àAMP + Pi, DG0= -7.7 or -32.2 kJ/mol. Highest energy phosphate is PEP.
6. There are three major sources of ~P taking part in energy conservation or energy capture:
· Oxidative phosphorylation: The greatest quantitative source of ~P in aerobic organisms. Free energy comes from respiratory chain oxidation using molecular O2 within mitochondria.
· Glycolysis: A net formation of two ~P results from the formation of lactate from one molecule of glucose, generated in two reactions catalyzed by phosphoglycerate kinase and pyruvate kinase, respectively.
· The citric acid cycle: One ~P is generated directly in the cycle at the succinyl thiokinase step.
7. Phosphagens act as storage forms of high-energy phosphate and include creatine phosphate, occurring in vertebrate skeletal muscle, heart, spermatozoa, and brain; and arginine phosphate, occurring in invertebrate muscle.
8. Cytochrome oxidase is a hemoprotein; the enzyme is poisoned by carbon monoxide, cyanide, and hydrogen sulfide. The cytochrome oxidase enzyme complex is known as cytochrome aa3. It contains two molecules of heme (2Fe) and 2 atoms of Cu.
9. Xanthine Oxidase and Aldehyde Dehydrogenase contains Molybdenum. Glutathione Peroxidase contains Selenium.
10. All cytochromes are classified as Dehydrogenases except Cytochrome Oxidase.
11. Enzymes of Mitochondria, Outer MM- 1. Glycerophosphate acyl transferase, 2.Acyl CoA Synthetase; Matrix 1. TCA Cycle enzymes 2.Beta Oxidation Enzymes 3. Pyruvate Dehydrogenase, Inner MM 1. ATP Synthase 2. ETC 3. Membrane Transporters.
12. The Electron transport Chain
· Complex I or NADH-Q-Oxidoreductase.
· Complex III or Q-cyt c-Oxidoreductase.
· Complex IV or cytochrome oxidase.
· Complex II or Succinate-Q- Reductase.
Q and Cyt-C are the mobile units. Complex I utilize 5H+. In Complex II (succinate -Q reductase), FADH2 is formed during the conversion of succinate to fumarate in the citric acid cycle. The chemiosmotic theory, proposed by Peter Mitchell, postulates that the two processes are coupled by a proton gradient across the inner mitochondrial membrane so that the proton motive force caused by the electrochemical potential difference (negative on the matrix side) drives the mechanism of ATP synthesis. Complexes I, III, and IV act as proton pumps.
13. The ATP Synthase complex consists of 2 subcomplexes F0 and F1. F1 is a fixed one containing 3 alpha and 3 bets subunits. ATP Synthase has a “bent-axle” consisting of Gamma and Epsilon subunits. F0 consists of multiple ‘C’ units arranged as a disc which rotates while protons pass through them, thereby rotating the axle also, resulting in the formation of 3ATPs from the Beta subunit in one turn.
14. When substrates are oxidized via Complexes I, III, and IV in the respiratory chain (i.e., via NADH), 2.5 mol of ATP are formed per half mol of O2 consumed; i.e., the P: O ratio = 2.5. On the other hand, when a substrate (e.g., succinate or 3-phophoglycerate) is oxidized via Complexes II, III, and IV, only 1.5 mol of ATP are formed; i.e., P:O = 1.5. These reactions are known as oxidative phosphorylation at the respiratory chain level. Most cells in the resting state are in state 4 of respiratory control, i.e., Availability of ADP only.
15. Inhibitors of ETC
Complex I: Amobarbital, Rotenone and Piericidin-A.
Complex II: Malonate, Carboxin and TTFA.
Complex III: BAL/Dimercaprol and Antimycin A
Complex IV: H2S, Cyanide and Carbon Monoxide.
Atractyloside inhibits oxidative phosphorylation by inhibiting the transporter of ADP into and ATP out of the mitochondrion.
Uncouplers dissociate oxidation in the respiratory chain from phosphorylation. E.g. ,4-dinitrophenol, Thermogenin, Oligomycin.
Thermogenin (or the uncoupling protein) is a physiological uncoupler found in brown adipose tissue that functions to generate body heat, particularly for the newborn and during hibernation in animals. The antibiotic oligomycin completely blocks oxidation and phosphorylation by blocking the flow of protons through ATP synthase.
16. The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADH:Q oxidoreductase (Complex I) or cytochrome oxidase (Complex IV) deficiency. It is caused by a mutation in mitochondrial DNA and may be involved in Alzheimer's disease and diabetes mellitus.
17. D and L isomerism: The designation of a sugar isomer as the D form or of its mirror image as the L form is determined by its spatial relationship to the parent compound of the carbohydrates, the three-carbon sugar glycerose (glyceraldehyde). Most of the monosaccharides occurring in mammals are D sugars. The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized light is passed through a solution of an optical isomer, it rotates either to the right, dextrarotatory (+), or to the left, levorotatory (–). The direction of rotation of polarized light is independent of the stereochemistry of the sugar, so it may be designated D(–), D(+), L(–), or L(+). For example, the naturally occurring form of fructose is the D(–) isomer. For glucose in solution, more than 99% is in the pyranose form.
18. Alpha and beta anomers: The ring structure of an aldose is a hemiacetal, since it is formed by combination of an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a hemiketal. Crystalline glucose is Alpha-D-glucopyranose. The cyclic structure is retained in solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom.
19. Epimers: Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose are known as epimers. Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2 and 4, respectively.
20. Excreted in the urine in essential pentosuria- L-Xylulose. An intermediate in the uronic acid pathway- L-gulonate. D-galactosamine is also known as chondrosamine.
21. Lactose may be excreted in the urine in pregnancy. Glycophorin is a major integral membrane glycoprotein of human erythrocytes.
Physiologically Important Lipids
22. Eicosapentaenoic Acid- Timnodonic Acid (fish oil), Docosahexaenoic Acid- Cervonic Acid (6 double Bonds).
23. Ergosterol occurs in plants and yeast and is important as a precursor of vitamin D.
24. Glycerol is a substrate for gluconeogenesis. The fatty acids are transported bound
to serum albumin; they are taken up by most tissues (but not brain or erythrocytes). In the liver, triacylglycerol arising from lipogenesis, free fatty acids, and chylomicron remnants is secreted into the circulation in very low density lipoprotein (VLDL).
25. Flux-Generating Reaction: It may be identified as a nonequilibrium reaction in which the Km of the enzyme is considerably lower than the normal substrate concentration. E.g. hexokinase.
26. Muscle preferentially takes up and metabolizes free fatty acids in the fasting state.
TCA Cycle
27. Isocitrate Dehydrogenase The decarboxylation requires Mg++ or Mn++ ions.
28. Succinyl-CoA is converted to succinate by the enzyme succinate thiokinase (succinyl-CoA synthetase). This is the only example in the citric acid cycle of substrate level phosphorylation. Tissues in which gluconeogenesis occurs (the liver and kidney) contain two isoenzymes of succinate thiokinase, one specific for GDP and the other for ADP. The GTP formed is used for the decarboxylation of oxaloacetate to PEP in gluconeogenesis, and provides a regulatory link between TCA activity and the withdrawal of oxaloacetate for gluconeogenesis.
29. Twelve ATP are formed per turn of the Citric Acid Cycle, three molecules of NADH and one of FADH2 are produced for each molecule of acetyl-CoA catabolized in one turn of the cycle.
30. Vitamins Play Key Roles in the Citric Acid Cycle 4: 1. Flavin-FAD for Succinate Dehydrogenase 2. Niacin NAD 3.Thiamine TPP for Isocitrate Dehydrogenase Decarboxylation 4. Pantothenic Acid – CoEnzyme A
31. Serine-Cystine-Threonine-Glycine-Hydroxyproline, Alanine (ßTryptophan): àà
Pyruvate.
32. Valine, Isoleucine and Methionine VIM be converted into Succinyl CoA, similarly
Tyrosine and Phenylalanine can be coverted into Fumarate.
33. Glutamine, Arginine, Proline and Histidine into GLUTAMATE then into alphaketoglutarate.
34. Glucokinase has a Km very much higher than the normal intracellular concentration of glucose.
pgmeedoubts@gmail.com
Newer Medicines 3: 31-41
31. Omapatrilat: Inhibits both ACE and Neutral Endopeptidase.
32. Pegaptanib: is a selective vascular endothelial growth factor (VEGF) antagonist, is indicated for the treatment of neovascular (wet) age-related macular degeneration.
33. Pemetrexed is a chemotherapy drug that interferes with three folic acid related enzymes (an antifolate antineoplastic agent), is indicated, in combination with Cisplatin, for the treatment of malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.
34. Perhexiline: pFOX (Fatty acid oxidase) inhibitor.
35. Raltegravir – is the first integrase inhibitor for drug resistant HIV infection.
36. Rifaximin - treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli in patients 12 years old and older.
37. Sorafenib is a multikinase inhibitor targeting a number of serine/threonine and receptor tyrosine kinases, is specifically indicated for the treatment of advanced renal cell carcinoma (RCC).
38. Tezosentan: Endothelin-1-Antagonist, Cardiac remodeling inhibitor.
39. Tipranavir is a non-peptide protease inhibitor which selectively inhibits virus-specific processing of viral Gag and Gag-pol polyproteins, preventing formation of functional mature virions.
40. Ularitide: Recombinant Urodilantin, a natriuretic peptide similar to ANP, BNP.
41. Zoledronic Acid: First one yearly therapy for Osteoporosis, for Paget’s disease and post-menopausal osteoporosis.
pgmeedoubts@gmail.com
Newer Medicines 2 : 21-30
21. Lapatinib : Kinase inhibitor used in metastatic breast cancer with HER2 overexpression.
22. Lenalidomide is an orally available thalidomide analog, exerting both anti-angiogenic and immunomodulatory/anti-inflammatory properties. Thrombocytopenia and neutropenia were the most frequently observed serious adverse events.
23. Lenalidomide: An IMID – Immunomodulatory derivative of Thalidomide.
24. Levosimendan: Calcium sensitizer.
25. Maprotiline: 2nd gen. antidepressant, with predominant NA reuptake inhibitor, little anticholinergic side effects, but may produce seizures.
26. Maraviroc – the first chemokine receptor antagonist, Entry Inhibitor for drug resistant HIV infection. Maraviroc blocks the main route of virus entry into uninfected cells—chemokine receptor 5 (CCR5).
27. Mecasermin contains recombinant-DNA-engineered human insulin-like growth factor-1 (rhIGF-1). It is designed to replace natural IGF-1 in pediatric patients who are deficient, promoting normalized stature growth. Patients with severe primary IGF-1 deficiency (Primary IGFD) fail to produce adequate levels of IGF-1, due to disruption of the growth hormone (GH) pathway used to promote IGF-1 release (possible GH pathway disruptions include mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects) and is specifically indicated for the long-term treatment of growth failure in pediatric patients with Primary IGFD or with GH gene deletion who have developed neutralizing antibodies to GH. It is not indicated to treat Secondary IGFD resulting from GH deficiency, malnutrition, hypothyroidism or other causes; it is not a substitute for GH therapy.
28. Modafinil: for patients with narcolepsy, sleep apnea, and shift work sleep disorder.
29. Natalizumab: recombinant humanized IgG4k monoclonal antibody produced in murine myeloma cells and is indicated for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations, 300 mg IV infusion every four weeks.
30. Nesiritide: Recombinant BNP.
pgmeedoubts@gmail.com
Newer Medicines 2 : 11-20
11. Darunavir: Protease Inhibitor.
12. Dofetilide: Potassium Channel Blocker.
13. Enoximone: PDE IIIa inhibitor (Amrinone/Milrinone)
14. Eplerenone: Aldosterone antagonist.
15. Etomoxir: pFOX (Fatty acid oxidase) inhibitor.
16. Guanfacine: a selective alpha-2A-adrenoceptor agonist of CNS for ADHD.
17. HPV Vaccine (GARDASIL) against HPV 6, 11, 16 and 18.
18. Irinotecan: Topoisomerase 1 inhibitor, called CPT-11, a Camptothecin molecule, anti-leukemia agent, also useful in Colon carcinoma, producing a metabolite SN-38 which produces secretory diarrhoea manageable with Loperamide or Octreotide, and also myelosuppression especially with patients with deficient UGT1A1.
19. Istaroxime: Na+/K+ -ATPase inhibitor (E.g. Digoxin), FIRST DRUG to target LUSITROPY.
20. Ixabepilone: Microtubule inhibitor for monotherapy for metastatic breast cancer after treatment failure with other agents.
pgmeedoubts@gmail.com
Newer Medicines 1 - 10
2. Ambrisentan: Endothelin receptor antagonist for treatment of pulmonary hypertension.
3. Anidulafungin: Echinocandin antifungal for treatment of candidemia, abcess, oesophagial candidasis.
4. Armodafinil : CNS stimulant, R-enantiomer of Modafinil
5. Atomoxetine: CNS noradrenaline (NA) reuptake inhibitor, first and only FDA approved non-stimulant drug for treatment of ADHD.
6. Bosentan: Endothelin-1-Antagonist, Cardiac remodeling inhibitor. Used for Rx of PPH.
7. Candoxatrilat: Inhibit Neutral Endopeptidase, increases ANP.
8. Carperitide: Recombinant BNP.
9. Cinacalcet - Cinacalcet is an oral calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. The calcium-sensing receptors on the surface of parathyroid gland cells also regulate parathyroid hormone (PTH) secretion. Increasing the sensitivity of these receptors results in lowering of PTH which subsequently lowers serum calcium levels. In addition, significant reductions in calcium may lower the threshold for seizures. Sensipar is an oral calcimimetic medication that lowers the levels of parathyroid hormone, phosphurous and calcium in patients undergoing kidney dialysis or in patients with parathroid cancer. Cinacalcet (Senipar) is indicated for the treatment of secondary hyperparathyroidism in chronic kidney disease patients on dialysis and the treatment of elevated calcium levels (hypercalcemia) in patients with parathyroid carcinoma. The recommended starting oral dose of Sensipar is 30 mg once daily.
10. Conivaptan is a non-peptide dual arginine vasopressin (AVP) V1A and V2 receptor antagonist. It is designed to inhibit the effects of AVP, also known as antidiuretic hormone (ADH), is specifically indicated for the treatment of SIADH. . In the kidneys, AVP's activity (primarily at V2 receptors) inhibits aquaresis, or excretion of free water. By exerting antagonistic activity at both V1A and V2 receptors, the drug is designed to inhibit inappropriate/excessive AVP secretion, thereby increasing rates aquaresis. Increased water secretion is correlated with net fluid loss, increased urinary output, and decreased urinary osmolality. Can cause hypokalemia, edema, pollakuria(daytime excessive urination)
pgmeedoubts@gmail.com
Skeletal Muscle Relaxants : Contd....
* SMR used in Asthmatics : Atracurium, Vecuronium.
* SMR used to reduce BP : d-TC.
* SMR used to maintain BP : Pancuronium.
* SMR which is cardiostable (commonly used) : Vecuronium.
* SMR safe in Hepatic Failure & Renal Failure : Atracurium, Cisatracurium.
* SMR contraindicated in Pregnancy and Renal failure : Gallamine.
* Pancuronium is Vagolytic and thus it can produce tachycardia.
That's all for now..
pgmeedoubts@gmail.com
CNS and Neurons
(CNS) contains about 10(raised to)11 (100 billion) neurons. It also contains 10–50 times this number of glial cells.
Protein Zero (P0) responsible for compaction of myelin, mutations of protein zero causes peripheral neuropathy. Nodes of Ranvier are 1micro meter in size placed 1 mm apart.
Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus, a process called accommodation.
Anelectrotonic-hyperpolarizing potential change, catelectrotonic- depolarizing potential change.
Absolute refractory period, corresponding to the period from the time the firing level is reached until repolarization is about one-third complete.
A decrease in extracellular Ca2+ concentration increases the excitability of nerve and muscle cells by decreasing the amount of depolarization necessary to initiate the changes in the Na+ and K+ conductance that produce the action potential.
Erlanger and Gasser Classification of Nerve Fibers into A, B, and C groups, further subdividing the A group into alpha, beta, gamma and delta fibers.
Maximum speed of construction A-delta fibers, maximum size for A-delta fibers.
Which are preganglionic autonomic fibers? Ans: Type B fibers.
A and B fibers are myelinated; C fibers are unmyelinated.
Protein Zero (P0) responsible for compaction of myelin, mutations of protein zero causes peripheral neuropathy. Nodes of Ranvier are 1micro meter in size placed 1 mm apart.
Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus, a process called accommodation.
Anelectrotonic-hyperpolarizing potential change, catelectrotonic- depolarizing potential change.
Absolute refractory period, corresponding to the period from the time the firing level is reached until repolarization is about one-third complete.
A decrease in extracellular Ca2+ concentration increases the excitability of nerve and muscle cells by decreasing the amount of depolarization necessary to initiate the changes in the Na+ and K+ conductance that produce the action potential.
Erlanger and Gasser Classification of Nerve Fibers into A, B, and C groups, further subdividing the A group into alpha, beta, gamma and delta fibers.
Maximum speed of construction A-delta fibers, maximum size for A-delta fibers.
Which are preganglionic autonomic fibers? Ans: Type B fibers.
A and B fibers are myelinated; C fibers are unmyelinated.
Neurons Classification and susceptility to pressure, anesthesia and hypoxia
Always expect one MCQ in physiology especially from the second portion of the chart.
Renin–Angiotensin System
- Renin is an aspartyl protease, contains 340 AA, t ½ <>
- After Nephrectomy the prorenin levels may actually rise (from ovaries), but rennin falls to 0.
- Angiotensinogen is found in the 2-globulin fraction.
- Angiotensinogen -> AT-I (decapeptide) -> (ACE) AT-II (octapeptide) in Lungs. ACE is a dipeptidyl carboxypeptidase that splits off histidyl - leucine from the physiologically inactive angiotensin I. AT II t ½ 1-2 minutes. The normal PRA in supine subjects eating a normal amount of sodium is approximately 1 ng of angiotensin I generated /mL/hr. The plasma angiotensin II concentration in such subjects is about 25 pg/mL (approximately 25 pmol/L).
- Dry Cough in ACEI is d/t increased Bradykinin.
- AT1 receptors are serpentine receptors coupled by a G protein (Gq).
- 1. JG cells (granular cells) - in the media of the afferent arterioles – intra renal pressure sensor, 2. Agranular lacis cells those are located in the junction between the afferent and efferent arterioles in the mesangium, 3. Macula densa (part of tubule – start of DCT, senses Na+) All 3 constitutes JGA.
- GOLDBLATT Hypertension – Syn. Renal Hypertension – decreased blood supply to one kidney -> increased renin.
Cerebral Blood Flow & Its Regulation
- Inhaled nitrous oxide (N2O) (Kety method). The average cerebral blood flow in young adults is 54 mL/100 g/min. The average adult brain weighs about 1400 g, so the flow for the whole brain is about 756 mL/min. In resting humans, the average blood flow in gray matter is 69 mL/100 g/min compared with 28 mL/ 100 g/min in white matter.
- Because brain tissue and spinal fluid are essentially incompressible, the volume of blood, spinal fluid, and brain in the cranium at any time must be relatively constant (Monro–Kellie doctrine).
- In the brain, auto regulation maintains a normal cerebral blood flow at arterial pressures of 65–140 mm Hg.
- O2 consumption by the human brain (cerebral metabolic rate for O2, CMRO2) averages about 3.5 mL/ 100 g of brain/min (49 mL/min for the whole brain) in an adult. This figure represents approximately 20% of the total body resting O2 consumption.
- Glucose enters the brain via GLUT 1 in cerebral capillaries.
- Blood Flow in Various Parts of the Brain – Best is P.E.T (2 Deoxy Glucose).
- CPP = MAP – CVP/ICP (whichever is higher), (Normal CPP 80-100 mmHg, ICP <10mm Hg.)
- Most important extrinsic influence on CPP is Arterial pCO2.
- Cerebral Blood Flow changes by 5-7 % with 10C change of temperature.
Wednesday, January 14, 2009
MONOCLONAL ANTIBODIES AND NEW DRUGS
1. Rituximab: Anti CD 20 / Anti B cell MAb. Human study underway for treatment of ANCA+ vasculitis.
2. Infliximab: Humanized Mouse Chimeric Anti TNFa (Rheumatoid Arthritis, Crohn’s)
3. Adalimumab: Fully humanized Anti TNFa (Rheumatoid Arthritis)
4. Etanercept: Recombinant TNF-receptor-Ig fusion protein Inhibit TNF-a (RA, JRA, Psoriasis).
5. Anakinra: Recombinant IL-1 receptor antagonist (IL-1Ra) : rheumatoid arthritis
6. OKT3: Anti-CD3 and T cell murine monoclonal antibody: Inhibit T cell function; induce T cell lymphopenia: treatment of cardiac and renal allograft rejection.
7. hOKT3 gamma-1: Humanized anti-CD3 monoclonal antibody: Eliminates auto-reactive T cells: Human study underway in Type I diabetes, psoriasis.
8. Daclizumab: Humanized anti-CD25 (IL-2R) monoclonal antibody, for graft versus host disease and UC (trial).
9. Omalizumab: Humanized anti-IgE monoclonal antibody, Human study underway for allergy (Hay fever, allergic rhinitis).
Will be updating
Dr.DV
Monday, January 12, 2009
X-Linked Dominant Diseases
Alport Syndome (Dominant inheritance) / Hereditary Nephritis Syndrome.
Incontinentia Pigmenti
Vitamin D Resistant Rickets / Hypophosphatemic Rickets
Double check before you study the following..
Rett syndrome
Coffin-Lowry syndrome
Aarsog Syndrome
Aicardi Syndrome
Idiopathic Hypoparathyroididsm
OTC Deficiency
X-Linked Recessive Diseases
Hemophilia A
Hemophilia B
G6PD Deficiency
Fragile-X Syndrome
Kallmann Syndrome
Adrenoleukodystrophy
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
CGD / Chronic Granulomatous Disease(Majority 70%)
Lesch-Nyhan Syndrome
Red Green Colour blindness
Ocular Albinism
Lowe's Oculo-Cerebro-Renal Syndrome
Wiscott-Aldrich Syndrome
SCID
Hunter's Syndrome (MPS)
Menke's Kinky hair disease
Fabry's Disease
Autosomal Recessive Diseases
Note : Majority of Inborn Errors of Metabolism are Autosomal Recessive.
PKU
Albinism
Galactosemia
Canavan' s Disease
Refsum's Disease
Abetalipoproteinemia
Ataxia Telengectasia
Friedrich's Ataxia
Familial Mediterranean Fever
ARPCKD
21-Hydroxylase deficiency
Werner Syndrome
Acrodermatitis Enteropathica (Zn Deiciency)
Kartagener's Syndrome
Refsum's Disease
Abetalipoproteinemia
Ataxia Telengectasia
Friedrich's Ataxia
Familial Mediterranean Fever
Alpha-1- Anti Trypsin deficiency
Cystic Fibrosis
ARPCKD
21-Hydroxylase deficiency
Bartter's Syndrome types 1,2,3 and 4 . (Type 5 is AD)(salt wasting, hypokalemia)
Gitelman variant of Bartter's (salt wasting, hypokalemia and HYPOMAGNESEMIA)
Wilson's Disease
Caroli's Disease
Caroli's Disease
Hemochromatosis (HFE gene)
CGD / Chronic Granulomatous Disease(Don't confuse it's only 30%)
Chediak-Higashi Syndrome
Specific Granule Deficiency
MPO Deficiency
Sickle cell Anemia
Chediak-Higashi Syndrome
Specific Granule Deficiency
MPO Deficiency
Sickle cell Anemia
Werner Syndrome
Acrodermatitis Enteropathica (Zn Deiciency)
Kartagener's Syndrome
Gyrate Atrophy
Autosomal Dominant Diseases
Tip1 : Majority of CNSdisorders are Autosomal Dominant, the major exception being Friedrich's Ataxia(AR)
Tip 2 : All Neurocutaneous syndromes/ Phacomatoses are AD except Ataxia Telengectasia.
MODY 1(HNF 4 alpha)
Familial Melanoma
Basal Cell Nevus Syndrome
Darier's Disease
Factor V Leiden Mutation
Neurofibromatosis 1 and 2
Von- Hippel-Lindau Syndrome
Sturge-Weber Syndrome
Tuberous Sclerosis
MEN 1 & 2
FAP
HNPCC / Lynch Syndrome
Gilbert's Syndrome
Alagille Syndrome
Peutz-Jeghers Syndrome
Turcot's Syndrome
Gardner's Syndrome
Juvenile Polyposis Syndrome
Hypertrophic Cardiomyopathy
Long QT Syndrome
Marfan Syndrome
Primary Pulmonary Hypertension(BMPR2 gene)
Adult AD Polycystic Kidney Disease
Familial Hypocalciuric Hypercalcemia
Neurohypophyseal Diabetes Insipidus
Familial Hyperaldosteronism
Bartter's Syndrome Type 5 (1,2,3 and 4 are AR)
Liddle's Syndrome
Gordon's Syndrome / Pseudo-hypoaldosteronism Type II
(Note : Liddle's - HTN with hypokalemia, Gordon's-- HTN with hyperkalemia)
Malignant Hyperthermia / Central Core Disease
Hyperkalemic Periodic paralysis
Familial Parkinsonism Disease
Spinocerbellar Ataxias
Dystrophia Myotonica/ Myotonic Dystrophy
Noonan Syndrome
Best Disease
Retinoblastoma
Malignant Hyperthermia / Central Core Disease
Hyperkalemic Periodic paralysis
Familial Parkinsonism Disease
Spinocerbellar Ataxias
Dystrophia Myotonica/ Myotonic Dystrophy
Noonan Syndrome
Best Disease
Retinoblastoma
Wednesday, January 7, 2009
Alagille syndrome : An Overview
Clinical
Physical
Presentation varies. Some patients are diagnosed after prolonged neonatal jaundice or when liver biopsy findings reveal paucity of intrahepatic bile ducts. Others may be diagnosed during evaluation for right-sided heart disease. Some individuals are diagnosed by careful examination after an index case is identified in the family.
- Nutrition and growth
- Children often present with poor linear growth.
- Altered longitudinal growth is attributed to wasting or inadequate intake, and an element of growth hormone resistance may also be present.6 Studies to assess the impact of higher doses of growth hormone on linear growth in patients with Alagille syndrome are currently underway.
- Head and neck
- Commonly associated facial features include broadened forehead, pointed chin, and elongated nose with bulbous tip.
- Characteristic facial features may not be obvious during infancy but may become more apparent as the child ages.
- Ophthalmologic
- Ocular abnormalities are common.7 The most frequent ophthalmologic finding is a posterior embryotoxon, which was observed in more than 75% of patients in one large series conducted by Emerick et al.8
- Some of these patients may also have the Axenfeld anomaly (ie, iris attachment to Descemet membrane).
- Other findings reported include retinitis pigmentosa, pupillary abnormalities, and anomalies of the optic disc.
- Cardiovascular
- Nearly all patients have cardiac murmurs.
- The most common cardiac lesions are stenoses within the pulmonary tree (peripheral pulmonic stenosis) with or without other structural lesions.
- Hemodynamically significant lesions include atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy of Fallot, patent ductus arteriosus (PDA), and pulmonary atresia (PA). Significant intracardiac lesions place patients with Alagille syndrome at increased mortality risk.
- Hepatic
- Hepatic disease is a key feature of Alagille syndrome.
- Most infants present with cholestatic jaundice.
- Hepatosplenomegaly is common.
- Elevations in serum bile acids often result in severe pruritus and xanthomas (hypercholesterolemia).
- Fat-soluble vitamin deficiencies, including coagulopathies and rickets, are frequent.
- Skeletal
- Abnormalities of the vertebrae, ribs, and hands are frequently associated with Alagille syndrome.
- Butterfly hemivertebrae were found in one half of the patients analyzed by Emerick et al in a large series of patients with Alagille syndrome.8
- Other isolated anomalies include rib anomalies and shortening of the radius, ulna, and phalanges.
- Neurologic
- Mild developmental delay and mental retardation are reported in some children with Alagille syndrome.
- If noted during the physical examination, diminished deep tendon reflexes should direct the clinician to exclude vitamin E deficiency.
- Renal: Occult renal artery stenosis, lipoid nephrosis, or glomerulosclerosis may present with signs and symptoms of chronic hypertension.
- Vascular: Vascular lesions have been recently described in 6% of the patients with confirmed Alagille syndrome who were followed by Kamath et al.9 These lesions included basilar artery aneurysms, internal carotid artery anomalies, middle cerebral artery aneurysm, Moyamoya disease and aortic aneurysms,coarctation of the aorta, and renal artery stenosis.
Causes
- Alagille syndrome is an autosomal dominant mutation with variable expression localized to the JAG1 gene (20p12).
- The JAG1 gene product functions as a ligand for the notch-1 receptor. In animal models, interactions between JAG1 ligand and notch-1 receptor play an important role in the determination of ultimate cell fate. Few patients, generally those with more severe phenotypes, have complete deletion of the JAG1 gene.
Sunday, January 4, 2009
What is USMLE STEP 3 ?
STEP 3
Step 3 is organized along two principal dimensions: clinical encounter frame and physician task (see Table 4). Step 3 content reflects a data-based model of generalist medical practice in the United States.
Encounter frames capture the essential features of circumstances surrounding physicians' clinical activity with patients. They range from encounters with patients seen for the first time for nonemergency problems, to encounters with regular patients seen in the context of continued care, to patient encounters in (life-threatening) emergency situations. Encounters occur in clinics, offices, skilled nursing care facilities, hospitals, emergency departments, and on the telephone. Each test item in an encounter frame also represents one of the six physician tasks. For example, initial care encounters emphasize taking a history and performing a physical examination. In contrast, continued care encounters emphasize decisions regarding prognosis and management.
USMLE Step 3 Specifications*
Clinical Encounter Frame
20%-30% Initial care
50%-60% Continued care
15%-25% Emergency care
Physician Task
8%-12% Obtaining history and performing physical examination
8%-12% Using laboratory and diagnostic studies
8%-12% Formulating most likely diagnosis
8%-12% Evaluating severity of patient's problems
8%-12% Applying scientific concepts and mechanisms of disease
45%-55% Managing the patient
- health maintenance
- clinical intervention
- clinical therapeutics
- legal and ethical issues
* Percentages are subject to change at any time. See the USMLE website for the most up-to-date information.
Primum® Computer-Based Case Simulations (CCS)
Step 3 examinees test using two formats: multiplechoice questions and Primum computer-based case simulations (CCS), a testing format that allows you to provide care for a simulated patient. You decide which diagnostic information to obtain and how to treat and monitor the patient's progress. The computer records each step you take in caring for the patient and scores your overall performance. This format permits assessment of clinical decision-making skills in a more realistic and integrated manner than other available formats.
In Primum CCS, you may request information from the history and physical examination; order laboratory studies, procedures, and consultants; and start medications and other therapies. Any of the thousands of possible entries that you type on the "order sheet" are processed and verified by the "clerk." When you have confirmed that there is nothing further you wish to do, you decide when to reevaluate the patient by advancing simulated time. As time passes, the patient's condition changes based on the underlying problem and your interventions; results of tests are reported, and results of interventions must be monitored. You suspend the movement of simulated time as you consider next steps. While you cannot go back in time, you can change your orders to reflect your updated management plan.
The patient's chart contains, in addition to the order sheet, the reports resulting from your orders. By selecting the appropriate chart tabs, you can review vital signs, progress notes, patient updates, and test results. You may care for and move the patient among the office, home, emergency department, intensive care unit, and hospital ward.
The cases used in the CCS portion of the Step 3 examination are based upon a CCS examination blueprint. The blueprint defines the requirements for CCS examination forms. The CCS blueprint is used to construct CCS examination forms focusing primarily on presenting symptoms and presenting locations. Presenting symptoms relate to the Step 3 Problem/Disease List and are associated with the central nervous system, eye/ear/nose/mouth/throat, respiratory system, circulatory system, digestive system, behavioral/emotional disorders, musculoskeletal system, skin/subcutaneous tissue, endocrine/nutrition/ metabolic disorders, kidneys/urinary tract, reproductive system, pregnancy/childbirth, neonate/childhood illnesses, blood and blood-forming organs, infectious/parasitic diseases, injuries/wound/toxic effects/burns, and health maintenance issues. Presenting locations include the outpatient office, emergency department, inpatient unit, intensive care unit, and the patient's home.
You will see cases related to some, but not all, of these problem/disease and location categories. The intent is to ensure that all examinees encounter a broad range of cases reflecting common and important symptoms and diagnoses. The selection of cases is also guided by specifications relating to age and gender. Each CCS examination form is structured to reflect a balance of cases that is fair and equitable for all examinees.
Details at www.usmle.org
Saturday, January 3, 2009
What is Step 2 CS and Step 3 CK?
STEP 2 CLINICAL KNOWLEDGE (CK)
Step 2 CK includes test items in the following content areas:
- internal medicine,
- obstetrics and gynecology,
- pediatrics,
- preventive medicine,
- psychiatry,
- surgery,
- other areas relevant to provision of care under supervision.
Most Step 2 CK test items describe clinical situations and require that you provide one or more of the following:
- a diagnosis,
- a prognosis,
- an indication of underlying mechanisms of disease,
- the next step in medical care, including preventive measures.
Step 2 CK is a broadly based, integrated examination. It frequently requires interpretation of tables and laboratory data, imaging studies, photographs of gross and microscopic pathologic specimens, and results of other diagnostic studies. Step 2 CK classifies test items along two dimensions: disease category and physician task, as shown in Table 2.
USMLE Step 2 CK Specifications*
Normal Conditions and Disease Categories
- Normal growth and development and general principles of care
- Individual organ systems or types of disorders
- immunologic disorders
- diseases of the blood and blood-forming organs
- mental disorders
- diseases of the nervous system and special senses
- cardiovascular disorders
- diseases of the respiratory system
- nutritional and digestive disorders
- gynecologic disorders
- renal, urinary, and male reproductive systems
- disorders of pregnancy, childbirth, and the puerperium
- disorders of the skin and subcutaneous tissue
- diseases of the musculoskeletal system and connective tissue
- endocrine and metabolic disorders
Physician Task
15%-20% Promoting preventive medicine and health maintenance
20%-35% Understanding mechanisms of disease
25%-40% Establishing a diagnosis
15%-25% Applying principles of management
* Percentages are subject to change at any time. See the USMLE website for the most up-to-date information.
STEP 2 CLINICAL SKILLS (CS)
Step 2 CS assesses whether you can demonstrate the fundamental clinical skills essential for safe and effective patient care under supervision. There are three subcomponents of Step 2 CS (see Table 3): Integrated Clinical Encounter (ICE), Communication and Interpersonal Skills (CIS), and Spoken English Proficiency (SEP).
The Subcomponents of Step 2 CS
Integrated Clinical Encounter (ICE)
- Data gathering - patient information collected by history taking and physical examination
- Documentation - completion of a patient note summarizing the findings of the patient encounter, diagnostic impression, and initial patient work-up
Communication and Interpersonal Skills (CIS)
- Questioning skills
- Information-sharing skills
- Professional manner and rapport
Spoken English Proficiency (SEP)
- Clarity of spoken English communication within the context of the doctor-patient encounter
Step 2 CS uses standardized patients, i.e., people trained to portray real patients. You are expected to establish rapport with the patients, elicit pertinent historical information from them, perform focused physical examinations, answer questions, and provide counseling when appropriate. After each interaction with a patient, you will record pertinent history and physical examination findings, list diagnostic impressions, and outline plans for further evaluation, if necessary. The cases cover common and important situations that a physician is likely to encounter in common medical practice in clinics, doctors' offices, emergency departments, and hospital settings in the United States.
The cases that make up each administration of the Step 2 CS examination are based upon an examination blueprint. An examination blueprint defines the requirements for each examination, regardless of where and when it is administered. The sample of cases selected for each examination reflects a balance of cases that is fair and equitable across all examinees. While the set of cases administered on a given day will differ from the set of cases administered on another day, each set of cases is comparable.
The intent is to ensure that examinees encounter a broad spectrum of cases reflecting common and important symptoms and diagnoses. The criteria that are used to define the blueprint and create individual examinations focus primarily on presenting complaints and conditions. Presentation categories include, but are not limited to, cardiovascular, constitutional, gastrointestinal, genitourinary, musculoskeletal, neurological, psychiatric, respiratory, and women's health. Examinees will see cases from some, but not all, of these categories. The selection of cases is also guided by specifications relating to acuity, age, gender, and type of physical findings presented in each case.
Friday, January 2, 2009
What is USMLE Step 1 ?
2009 USMLE Bulletin - Examination Content
STEP 1
Step 1 includes test items in the following content areas:
- anatomy,
- behavioral sciences,
- biochemistry,
- microbiology,
- pathology,
- pharmacology,
- physiology,
- interdisciplinary topics, such as nutrition, genetics, and aging.
Step 1 is a broadly based, integrated examination. Test items commonly require you to perform one or more of the following tasks:
- interpret graphic and tabular material,
- identify gross and microscopic pathologic and normal specimens,
- apply basic science knowledge to clinical problems.
Step 1 classifies test items along two dimensions, system and process....given below.
USMLE Step 1 Specifications*
System**
40%-50% General principles
50%-60% Individual organ systems
- hematopoietic/lymphoreticular
- nervous/special senses
- skin/connective tissue
- musculoskeletal
- respiratory
- cardiovascular
- gastrointestinal
- renal/urinary
- reproductive
- endocrine
Process
30%-50% Normal structure and function
30%-50% Abnormal processes
15%-25% Principles of therapeutics
10%-20% Psychosocial, cultural, occupational and environmental considerations
* Percentages are subject to change at any time. See the USMLE website for the most up-to-date information.
** The general principles category includes test items concerning those normal and abnormal processes that are not limited to specific organ systems. Categories for individual organ systems include test items concerning those normal and abnormal processes that are system specific.
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