Lesch Nyhan syndrome - Mechanisms (Revised post)

 Hello friends! Let's refresh our biochemistry knowledge today.

Lesch-Nyhan syndrome is characterized by choreoathetosis, dystonia, hyperuricemia, gout, self mutilatory behavior especially self-biting of fingers, and intellectual disability due to HGPRTase mutations.

So how do HGPRTase mutations actually cause dystonia and other extrapyramidal signs and symptoms?

1.)  For the synthesis of dopamine, tetrahydrobiopterin as a cofactor for tyrosine hydroxylase is required.
Tetrahydrobiopterin itself is derived by a series of reactions in which GTP cyclohydrolase is a rate-limiting enzyme.
Now HGPRTase deficiency causes depletion of GTP thereby ultimately depleting tetrahydrobiopterin.

In fact, GTP cyclohydrolase mutations are known to cause dopa-responsive dystonia and phenotype similar to Lesch-Nyhan syndrome.

2.)  Secondly, dopamine receptors are linked to G-protein coupled receptors which alternate between GTP-GDP bound states, yet another link between GTP depletion and perturbation of dopamine signaling.

3.) Adenosine deficiency due to the reduction in salvage may adversely affect the role of adenosine as a neuroprotective agent.

Lastly, in Lesch Nyhan syndrome no characteristic imaging abnormalities are seen but reduced dendritic arborizations in the caudate nucleus, putamen, and nucleus accumbens are thought to underlie clinical manifestations.

So to summarise, Lesch Nyhan syndrome can be considered as one of the basal ganglia disorders with Wilson's disease and Huntington's disease being the other notable ones.

Have a great day!

-Kirtan Patolia

Celiac Disease (Spectrum of Manifestations)

 Hello friends! I hope all of you are doing well. Today I wanted to share with you the many faces of Celiac Disease. Although considered as the disease which chiefly causes gastrointestinal symptoms, the entire spectrum of possible manifestations it can cause is quite broad.

Some significant associations are as follows:

1.) GI- Enteropathy associated T-cell lymphoma (EATL), Microscopic colitis

2.) Liver- NASH

3.) Spleen- Functional Asplenia (SLE & Amyloidosis being other notable causes)

4.) CNS- Seizures with posterior cerebral calcification, Neuro-psychiatric symptoms, Ataxia

5.) Hematology- Evans syndrome

6.) Pulmonary- Diffuse alveolar hemorrhage

Here is the full spectrum. Hope you like it.

-Kirtan Patolia

Overview of methods of haemostasis in surgery

Contrast induced nephropathy

 

Hormone Basics - Part 1

 Hormones are divided into 2 groups

Group 1 hormones- Act via nuclear receptors

    Type 1- Have cytoplasmic receptors with effector elements in the nucleus e.g Steroid hormones (cortisol), Gonadal hormones (Androgens, estrogens, progesterones)

Mnenonic- There is only 1 General Secretary

  Type 2 -Directly act at the nucleus e,g, vit D,vit A, Thyroxine

Mnemonic-Directly AcT at the nucleus

Group 2 hormones-  Act via the cell membrane surface receptors

1. GPCR- Very extensive, will require a second post

2.Tyrosine Kinase- All Growth factors(Except TGF alpha and beta) and Insulin (Tip to remember: TKI or tyrosine kinase inhibitors are used in a lot of malignancies, there's abnormal growth in malignancies and hence TKIs stop that growth, also I in TKI will remind you of insulin, Insulin causes fat to grow!!)

3. JAK-STAT(cytokine receptor) Mr. JAcK is a Drunkard!! all he needs is PEG 

Prolactin, 

Erythropoietin, 

Growth hormone.

(Pro tip: GH and PRL are called as twin hormones, JAK STAT mutations are involved in Myeloproliferative disorders say Polycyathemia and erythropietin is needed there)

4.Serine threonine Pathway: This pathway is a perfect BAIT for the hormones.

Bone morphogenic protein  

Activin

Inhibin

Trasformation growth factor alpha and beta

That's all for today!

Have fun and stay safe!

How did you find the post?

Let me know in the comments section below!

Dr. ShilPill

Osler's triad mnemonic

 

Thank you!

Reactive arthritis mnemonic

 

Thank you!

Dizziness & Vertigo | Harrison’s IM

IgG4-related systemic disease mnemonic

It is chronic disease characterized by fibrosis and sclerosis of various tissues due to infiltration with lymphocytes that secrete IgG4. Manifestations include sclerosing sialadenitis, retroperitoneal fibrosis, autoimmune pancreatitis, Riedel thyroiditis, tubulointerstitial nephritis, and other fibrosclerotic conditions.

That's all!

Thank you. 

Dengue classification

•   Dengue from Harrison’s IM  https://youtu.be/MYVxisW4EPw

WHO 1997 classification :

Dengue fever —  >2 of the following 

●Headache

●Retro-orbital or ocular pain

●Myalgia and/or bone pain

●Arthralgia

●Rash

●Hemorrhagic manifestations (eg, positive tourniquet test, petechiae, purpura/ecchymosis, epistaxis, gum bleeding, blood in emesis, urine, or stool, or vaginal bleeding)

●Leukopenia

Dengue hemorrhagic fever — The cardinal feature of DHF is plasma leakage due to increased vascular permeability as evidenced by hemoconcentration (≥20 percent rise in hematocrit above baseline). In the setting of DHF, the presence of intense abdominal pain, persistent vomiting, and marked restlessness or lethargy, especially coinciding with defervescence, should alert the clinician to possible impending DSS.

According to the guidelines, a DHF diagnosis requires all of the following be present:

●Fever or history of acute fever lasting 2 to 7 days, occasionally biphasic 

●Hemorrhagic tendencies evidenced by at least one of the following:

•A positive tourniquet test – The tourniquet test is performed by inflating a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressures for 5 minutes. A test is considered positive when 10 or more petechiae per 2.5 cm (1 inch) square are observed. The test may be negative or mildly positive during the phase of profound shock. It usually becomes positive, sometimes strongly positive, if the test is conducted after recovery from shock.

•Petechiae, ecchymoses, or purpura.

•Bleeding from the mucosa, gastrointestinal tract, injection sites, or other locations.

•Hematemesis or melena.

●Thrombocytopenia (100,000 cells per mm3 or less) –  In healthy individuals, 4 to 10 platelets per oil-immersion field (100x; the average of the readings from 10 oil-immersion fields is recommended) indicates an adequate platelet count. An average of 3 platelets per oil-immersion field is considered low (ie, 100,000 per mm3).

●Evidence of plasma leakage due to increased vascular permeability manifested by at least one of the following:

•A rise in the hematocrit equal to or greater than 20 percent above average for age, sex, and population.

•A drop in the hematocrit following volume-replacement treatment equal to or greater than 20 percent of baseline.

•Signs of plasma leakage such as pleural effusion, ascites, and hypoproteinemia.

Dengue shock syndrome — DSS consists of DHF with marked plasma leakage that leads to circulatory collapse (shock) as evidenced by narrowing pulse pressure or hypotension.

●Rapid and weak pulse.

●Narrow pulse pressure ( ≤20 mmHg) or manifested by: observed early in the course of shock.

•Hypotension for age – observed later or in patients who experience severe bleeding.

Hypotension is defined to be a 

• SBP 80 mmHg  for those < 5 years of age 
• SBP 90 mmHg  for those equal to or > 5 years of age.

•Cold, clammy skin and restlessness.

WHO 2009 classification — 

Dengue without warning signs —>2 of the following 

●Nausea/vomiting

●Rash

●Headache, eye pain, muscle ache, or joint pain

●Leukopenia

●Positive tourniquet test

Dengue with warning signs —  any of the following 

●Abdominal pain or tenderness

●Persistent vomiting

●Clinical fluid accumulation (ascites, pleural effusion)

●Mucosal bleeding

●Lethargy or restlessness

●Hepatomegaly >2 cm

●Increase in hematocrit concurrent with rapid decrease in platelet count

Severe dengue —at least one of the following :

●Severe plasma leakage leading to:

•Shock

•Fluid accumulation with respiratory distress

●Severe bleeding

●Severe organ involvement:

•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1000 units/L

•Impaired consciousness

•Organ failure

1. Sudden high-grade fever (≥38.5°C) Children have high fever but are generally less symptomatic than adults during the febrile phase. The febrile phase lasts for three to seven days, after which most patients recover without complications. 
2. What is Biphasic fever ("saddleback") ?  - 1st febrile phase remits & recurs approx 1 to 2 days later & this 2nd febrile phase lasts 1 to 2 days.
3. Serum aspartate transaminase (AST) levels are frequently elevated; the elevations are usually modest (2 to 5 times the upper limit of normal values), but marked elevations (5 to 15 times the upper limit of normal) occasionally occur.
4. Between days 3 and 7 of the illness, you must watch for signs of vascular leakage. Corresponding clinical manifestations may include persistent vomiting, increasingly severe abdominal pain, tender hepatomegaly, development of pleural effusions and/or ascites, mucosal bleeding, and lethargy or restlessness; laboratory findings may include a high or increasing hematocrit level (≥20 percent from baseline) concurrent with a rapid decrease in the platelet count
5. The vast majority of DENV infections that progress to a critical phase result from secondary infections more than 18 months after the first infection.The critical phase lasts for 24 to 48 hours.

Thank you! 🫀🩺

Study smarter not harder- Active recall, the foolproof method to ace any test

 If I ask an average student about their preferred study strategy the answer most likely would be Highlighting, summarising, and re-reading. Making aesthetically pleasing notes in a myriad of colours may be appealing to many but is passively re-reading already familiar content an effective study strategy?

Two of the most effective study strategies I have come across are active recall and spaced repetition. In this post, I will be talking about the science behind this method. I’ll cover spaced repetition in another post.

Complete Androgen Insensitivity- A perfect female

 Hello everyone!

In today's post I'll try to explain you what Complete Androgen Insensitivity Syndrome (CAIS) is.

Androgens are primarily male hormones required for a normal male development. But also, these androgens are secreted in females by their adrenal glands and have some role in female body development too, e.g Growth of pubic and axillary hair.

Now imagine, a very very beautiful adolescent girl, say around 16 years of age, comes to your clinic with a history of primary amenorrhoea. She has absolutely flawless skin (No acne like other 16yr olds), breast development normally, no pubic and axillary hair and on further examination, some inguinal mass, maybe a hernia.

You ask the radiologist for an USG abdomen and pelvis. Don't be surprised to find testes as the hernia content and no uterus!!

This is a classic case of CAIS.

Karyotype analysis- 46XY

Inheritance- XL recessive, mutation in the AR (Androgen Receptor) gene

Genitalia- Female with blind vaginal pouch

Wolffian duct- Often present

Mullerian Duct- Absent

Gonads- Testes

Hormone Profile- Increased LH and Testosterone (But the receptors have resistance to it's action)

Increased Estradiol, FSH slightly raised.

For more pictographic representation, Watch HOUSE MD S02E13 "Skin deep"

That's it!

Happy Studying

Stay awesome!

Dr. ShilPill

How to write a Personal Statement for Residency

 

How to write a Personal Statement for residency

How to begin

1. Daily start writing down ideas in Evernote/any app which lets you take notes
2. Think of a strong patient interaction/personal story where you helped the patient and which also shows your medicine-related skills/knowledge/work ethic. Make it about yourself, what you did, and how it helped you. Do not write the entire history of the patient.
3. Either with the same story as above or explain the reason/reasons why you are interested in that particular field.
4. Make a list of your hobbies/ non-medical experiences and find a common connection between that skill set, which can actually help you during residency.
5. Read loads of sample personal statements from google!!!
6. Do not copy them (plagiarism is HARMFUL). 
7. Once you are done, send your draft to mentors/English professors/seniors etc.
8. Make sure there are absolutely no grammatical errors. (English being a 2^nd language is not an excuse for poor grammar).

 

Don’t’s

•        This is not the time to show off your creative writing skills. We are applying for a residency, not a literature graduate position. Keep it simple and easy to read.

•        Do not use super-long sentences. IMGs have a tendency of using a lot of ‘and’ and writing 3-4 line long sentences. Keep it short.

•        Target content that fits into one page. 600-700 words approx. Don’t go over 800, don’t stay under 500.

•        Do not use negative incidents/ bad mouth your home school or resources.

•        Don’t lie. You will get caught. If you say you have worked on multiple research projects and if you are unable to answer basic questions regarding your research, you WON’T be selected.

•        You never know how much importance programs give to the PS, so always make sure it is a well-written PS.

•        Don’t quote your CV.

•        Don’t use clichés or common quotes.

•        Don’t start every sentence with “I.”

•        Come across as arrogant. This is the place to showcase your strengths, but in a humble way.

 

 

How to divide paragraphs: 1^st paragraph

•        The first and last paragraphs are the most commonly read parts. Make them interesting and strong. It should be personalized.

•        Begin strong: Story/Hobby/What got you into medical school or you can skip that and talk about what got you interested in your specialty.

•        It should be a story about yourself and how it relates to your specialty, not just a history of the patient you saw.

 

DON’T’s

·        “Every patient has a story to tell.”

·        Some major illness in the family/ death motivated me to become a physician.

·        “I love to travel. Each journey takes us down a different path. Each journey inspired a new thought. I feel medicine is similar to traveling. Every patient has his own journey and I want to be there to make it fruitful for them.” (This is not the right analogy. Travel and medicine have nothing in common)

·        “I will never forget ___”

·        “I grew up with dermatology in my blood”

 

DO’s

·        “Growing up in rural ____, I experienced ____. Here I realized _____. The strict value system of perseverance and dedication led me to ____.”

·        Start with your hobby.
E.g. Football….team sport….captain of the football team….motivated my team, resolved conflicts. At the same time I realized, that whenever someone got hurt, I would assist my coach with first aid. I realized that my inclination for helping my injured team mates extended beyond the football field. Bridge it into medical school and how you continued doing the same. Got you interested in EM/ortho etc.

·        “Medicine is a field in which my love for pathophysiology and my commitment to serving others can continue to grow. I have a strong desire to use my problem-solving abilities while helping people through their most difficult times.” And then give an example justifying these 2 statements.

 

 

How to divide paragraphs: 2^nd, 3^rd and 4^th paragraphs

•        Talk about your strengths in a very SUBTLE way, citing examples.

•        Talk about your achievements and extra curriculars, your motivation and end it with what skill-set you derived from it.

•        Include hobbies. Connect them with medicine and how it will make you a better resident.

•        Relate how your actions and experiences during medical school will make you a strong physician.

•        What will you bring to their program?

•        Don’t quote your CV.

•        Show who you are as a person, not just as an ideal medical student.

 DO’s

•        Talk about your strengths in a very SUBTLE way, citing examples.

•        Talk about your achievements and extra curriculars, your motivation and end it with what skill-set you derived from it.

•        Include hobbies. Connect them with medicine and how it will make you a better resident.

•        Relate how your actions and experiences during medical school will make you a strong physician.

•        What will you bring to their program?

•        Don’t quote your CV.

•        Show who you are as a person, not just as an ideal medical student.

 DON’T’s

·        I love IM as it is such a broad field with a vast number of diseases.
(Same goes for FM and Peds and all other branches. Avoid such blanket statements.)

·        I want to be trained to manage patients on my own and do right by them to be one of the best in my field.
(Umm…isn’t this what residency is about. Everyone wants that. What is it that you are specifically looking for?)

·        Also, avoid “I love” “I want to”

·        “IM combines the wide spectrum of exotic and the mundane illness, providing a scope of touching maximum lives.”
Do you mean to say FM/EM/ortho/surgery etc. do not provide this?

·        “My mentor taught me more about medicine and how to approach a patient better than I had learned in all of my classes.”
Do not put your other classes in a negative light.

 

 

How to divide paragraphs: last paragraph

•        Summerise.

•        Tie in all your major attributes.

•        Talk about: What you are looking for in a program

•        Talk about: Where do you see yourself in a few years?

 DO’s

•        I will bring to residency energy, enthusiasm, integrity, and ability. I expect a challenging, rich environment in which to learn and practice good medicine.

•        I know I have set high goals for myself: clinician, educator, and health advocate. The majority of the time I find working with underserved populations extremely rewarding; however, it can also be emotionally demanding.

•        The combination of working at an individual level to address health needs and at a more macroscopic level to affect health policy is synergistic for me.

•        I eagerly await the unique privilege of participating in such a rewarding and exciting field of patient care.

 DON’T’s

•        Don’t be too specific regarding fellowship goals unless you are absolutely sure.

•        If you are sure regarding your fellowship, your CV should have enough experience to back it up.

•        “Medicine encompasses numerous areas that I have always found intriguing. Becoming a physician is a lifelong dream that will fulfill both my personal and career goals.”
What are the goals? State them. What are the intriguing areas? It is a vague sentence. Avoid fluff.

•        “My career goal is to enter a university-based anesthesiology program.”
Then community programs (forming a major chunk of interviews for IMGs, will not call you for an interview. Be diplomatic.

Time Frame

 •        June 1^st half: Begin jotting down ideas and writing sentences. Focus on ideas. Don’t worry about sounding smart/grammar right now.

•        June 2^nd half: Start compiling the ideas and sentences into paragraphs. Check the flow. Keep reading samples to understand how to write it.

•        July 1^st half: Make your 1^st draft. Send it to seniors/attendings/mentors.

•        July 2^nd half: Incorporate the changes suggested by them and make another draft.

•        Aug 1^st half: Send it out for suggestions again.

•        Aug 2^nd half: Make a final draft. Here your ideas, stories, hobbies, major points should be finalized and free-flowing. Now run a final grammar check. Send it to someone with professional level English for edits and grammar.

•        Sept 1^st week: Final draft ready

 

Take away

•        Personal Statements might not fetch you interviews unless it is extra-ordinary. You will get interviews based on your scores and other aspects of the application.

•        You may lose out on an interview due to a bad PS. (Incorrect grammar, poorly written)

•        Interviewers love to talk about the hobbies mentioned in the personal statement, so make sure they are real!!

•        They are looking to know you as a person, so make sure your PS does not describe 1000s of other medical students as well.

•        Once you land an interview, the PS might play a role in getting you ranked high. The program wants a candidate that would ‘Match’ their expectations!