Mechanism of action of Everolimus in breast cancer

Hello!

Did you guys know that everolimus, an immunosuppressant, is used for cancers like renal cell carcinoma, pancreatic neuroendocrine tumors, etc?

The mechanism of action is really cool, especially in ER (Estrogen receptor) +ve, HER2 -ve breast cancers.

Sometimes ER +ve tumors develop resistance to endocrine treatment such as aromatase inhibitors.

The mechanism of endocrine resistance is mainly driven by aberrant signaling along the phosphoinositide 3-kinase (PI3K) - Akt - mammalian target of rapamycin (mTOR) signaling pathway. mTOR is a Ser/Thr protein kinase that constitutes a central downstream part of this intracellular signaling pathway. Its activation enhances cell growth, proliferation and metabolism, and promotes angiogenesis. The inhibition of the mTOR pathway by targeted therapies, such as everolimus or temsirolimus, can therefore block tumor growth and induce apoptosis.

Isn't that awesome?

-IkaN

ACE Inhibitors in Diabetic Nephropathy

Whats the role of ACE inhibitors in diabetic nephropathy?
I was asked this question in viva..

》ACE Inhibitors retard the progression of Diabetic Nephropathy.
Here is the mechanism-

Renin-Angiotensin system (RAS) gets activated in Diabetes (both type 1 and 2). So there is increased production of Angiotensin and its products, which leads to various vascular and metabolic changes.
Angiotensin-II induces several fibrogenic chemokines, viz.
Monocyte Chemo attractant Protein-1 (MCP-1) and Transforming Growth Factor- beta (TGF-B)
AT-II activates transcription factors
Nuclear factor-KB and thus synthesis of MCP-1 in renal cells. MCP-1 has a role in monocyte immigration which transmigrates through vascular endothelium and gets differentiated to macrophages. This leads to increased Extracellular Matrix production and Tubulo Interstitial Fibrosis.

Slow acting drugs like Lisinopril, Enalapril, Ramipril are employed for 12 months therapy in Diabetic Nephropathy. Assessment of proteinuria, creatinine clearance, uMCP-1 is done before and after this period.
A decrease in protein content in urine, increase in creatinine clearance, and a massive decrease in urinary MCP-1 levels are seen.

Angiotensin Receptor Blockers also retard the renal damage in type 1 and type 2 diabetes.

That's all!
Thanks :)

- JasKunwar Singh

ACE Inhibitor (Captopril) Adverse effects mnemonic

Let's memorize from the name itself-
CAPTOPRIL :

C Cough
A Angioedema/ Agranulocytosis
P Proteinuria/ Potassium excess
T Taste changes ( Dysguesia )
O Orthostatic Hypotension
P Pregnancy/ Pancreatitis/ Pressure drop
R Renal failure and Renal Artery stenosis (contraindicated) / Rash
I Indomethacin inhibition
L Leukopenia/ Liver toxicity.

Hope now you won't forget it. ;)
Thanks!

- JasKunwar Singh

Of reservation, proving yourself and deserving things

"Hello IkaN,

First of all I'd like to tell you how amazing your blog is and how glad I am to have found it.

I am in first year at a government medical college. But I don't deserve to be there. I have reservation (Yes, THAT hated word). I am also well aware that I probably took this seat from someone who scored more than me. The feeling of being less first hit me in the first month of college, when I saw a lot of people speaking out against reservation. 

I wanted to be a doctor. But not like this. The self loathing got so much so that I considered dropping out but I couldn't ask my parents to pay the bond just because I got exactly what I wanted just not in the way I wanted. Nobody in college is as such discriminating towards me but I know they feel a bit differently if they knew how I got here. 

It hinders my studies. I don't feel the same amount of interest in becoming a doctor as I did before. My parents want me to study well, even get a post graduate degree but I can't bear the thought of living all my life in the shadow of reservation.  

I don't want to sound ungrateful for the opportunity I have been given. Being a doctor is a prestige few people get and I know I'm lucky to have got it. I just wish it would have been differently. Which is why I wanted to apply for USMLE.. At least there, things would be fair. If I got something I would know it was because I deserved it. But then I wonder if I couldn't even get an undergraduate seat by myself how would I manage a post graduate one especially one in America ?

I'm not poor but neither am I rich. I don't know how much the exam fees and the books required to study for the exam cost but I'm pretty sure it is not cheap. And if after giving the exam I fail, what would I do?

I really hope you reply but I would understand if you can't because of time constraints or because you don't want to. Thank you for your time either ways."

- Sent through email. 

Aromatase inhibitors and ER positive breast cancer

Happy Monday everyone!

Why are aromatase inhibitors effective in post menopausal women who have breast cancer and why not in women who are premenopausal?

I was asked this question during rounds.

Sturge- Weber syndrome

Hello

Talking about this rare syndrome, I read about in ophthalmology lecture (class of secondary glaucomas) today... So let's start with it-

- It is also known as Encephalo Trigeminal  Angiomatosis (ETA)
• Rare congenital Neurological and skin disorder (phakomatoses)
• Caused by Somatic Acivating Mutation in GNAQ gene.

• Port -wine stains (nervus flammeus) - 
            ○ Usually seen on Forehead and Upper Eyelid of one side of face; present since birth.
            ○ Light Pink to Deep Purple
            ○ Caused by Overabundance of capillaries  around Ophthalmic branch of Trigeminal nerve.

• Associated with
          ○ Secondary Glaucoma (in 50% patients)
          ○ Buphthalmos (enlarged eyeball due to increased intraocular tension)
          ○ Leukocoria (white pupillary reflex)
          ○ Neurologic manifestations- seizures, convulsions (on side of body opposite to birth mark), mental retardation, calcification of tissue and loss of nerve cells in cerebral cortex.
          ○ Ipsilateral Leptomeningeal Angioma (on same side of birth mark; calcification of underlying brain and atrophy of affected region)
• Malformed blood vessels in the piamater overlying the brain on same side of head as the birthmark.

• Radiological appearance shows Tram-Track Appearance on CT, bilaterally.

• Treatment strategies include Laser surgery, Hemispherectomy
 - Latanoprost, a Prostaglandin analogue, is suitable drug for decreasing intra ocular pressure. (1 drop daily in evening)

That's all
- Jaskunwar Singh

An Eye to Cyanide - Part 2

Hello awesome people :)

So, talking about differentials for the cyanide case.. (see previous post Here)

What all u can guess could be the case in such patient if not cyanide..?? Anyone? Think before you read it further..

Here it is...

It could be Carbon Monoxide poisoning. Reason? OK so you remember the patient had shown Cherry Red color of skin when she was brought to the emergency. Carbon monoxide also causes such discoloration of skin as well as blood. This is due to formation of carboxyhemoglobin, which causes decrease in oxygen carrying capacity of blood. So less supply of oxygen and essential nutrients to brain as well as other vitals of the patient, leading to neurological, cardiac as well as other systemic problems!!

An Eye to Cyanide

Hello awesomites!

Hope your weekend is going well :D

I just read about a case of cyanide poisoning and learnt some important points related to it. So here it is -

"A 27 year old comatose woman was brought to emergency by paramedics, and a strong odor of bitter almonds is present. Her past medical history is significant for malignant hypertension. For the past few months, she was given injections of sodium nitroprusside for the treatment, according to her accompanying relatives. She is a housewife and has been under stress regarding family problems. Also she had consumed few almonds a day ago."

Do it for the better, to achieve your Best!!!

Thinking of starting something new? That's great! Don't wait, just start it. Open the first page. C'mon you can do it. Haha.. don't worry. I know it's difficult, but trust me once you start it, you will enjoy it. Yes you will.

Remember one thing always.. Consume your time in doing something productive. Keep yourself busy in some task, create new ideas, think about something and do it. Dream a lot. Yes you really should.

Do it for the betterment of society. Do it for yourself. To achieve the best of yourself. Trust me, the day when u do that, you will feel really happy. Because you did what you wanted to. That you loved. You lived!!!

Thanks! :)
-Jaskunwar Singh.

Step 2 CS: Challenging questions

Here are some of my sample closures for challenging questions.

All my closures are generic with little word play. Whatever the SP says, I would say it back to them saying I understand it. So your sympathy - empathy is done.

See how all three closures are almost the same - 

"Will I need surgery?"
I understand that you are concerned about the possibility of having a surgery. Yes, you might require a surgery. But I assure you that we will be there to support you, throughout the treatment, regardless of the diagnosis. Does that sound okay to you?

Step 2 CS: Introduction

Here's how I introduced myself -

"Mr. Smith? Hi. I am doctor D. I'm the attending physician and I'll be taking care of you."

"Are you comfortable in the room?" (Yes.)

"May I take a seat and write a few notes as we talk?" (Yes.)
"So can you tell me what brought you to the clinic?" (Blah blah blah...)
"Can you tell me more about it?"

Step 2 CS: Counselling for PTSD

I can see that you are distressed about an event that occurred in your life. We have some medical therapy available that can help you with this. Medicines take time to work, in the mean while I can get you in touch with some support groups and social help organizations that have patients who have witnessed similar traumatic events in their life.

Step 2 CS: Physical exam findings in a patient with calf pain

We were practicing a case of calf pain (DVT / cellulitis) today and my friends told me that I documented the physical examination findings well, which is why I posted the note on the blog :)

Things in brackets are for reference only and I didn't type those in my 10 minutes encounter.