May 22, 2016

god has a horrible sense of humor

I am signing an order that needs the date and time so I ask the nurse. "May 22nd". Of course. Why else would my very first patient in the ER be one suffering from the horrific pain that bone metastases inflict? At the end of my shift, I was able to get them admitted to the hospital. And got a thumbs up from the patient. I will not elaborate upon what Herculean (and self alienating) measures were required to get to that point where a thumbs up is the best possible outcome one could wish for as a doctor. Instead, I look down at my left wrist, my familiar and well worn Mala beads rolled comfortably around my wrist. I roll one unnoticeably in between my thumb and forefinger, close my eyes, and become grounded to these ancient words which arose from my memory five years ago on a Sunday morning at 3:30 am. 

Through many countries and over many seas
I have come, Brother, to these melancholy rites,
To show this final honour to the dead,
And speak (to what purpose?) to your silent ashes,
Since now fate takes you, even you, from me.
Oh, Brother, ripped away from me so cruelly,
Now at least take these last offerings, blessed
By the tradition of our parents, gifts to the dead.
Accept, by custom, what a brother’s tears drown,
And, for eternity, Brother, ave atque vale
‘Hail and Farewell.’

May 20, 2016

an old man

     You can barely see them.  The four little dots of a band aids on my lower right back.  They represent yet another round of poking needles into my spine all in a desperate attempt to bring some modicum of relief from pain.  Most people can't tell I am in pain nearly every day.  I have become very good at hiding it. 
     When I check in at the front desk of the doctor's office, everyone has to fill out a form saying they will not drive and that someone can drive them home after the procedure.  But me?  I don't drive.  I walk.  I go back to work.  Besides who wants to know their doc is human?  We are supposed to be Superman, after all.  But my doc, who is incredibly talented with an amazing staff, can see the pain and the exhaustion it brings with it in my eyes today.  We both know we are reaching the end of what procedures are available to me. 
     "Am I even helping?  I want to make sure that I am actually helping you."
     "Well, since ablating the nerves on the left side, I can check my left blind spot a lot easier.  That's something.  But my pain?  The worst is deep down in that joints of that extra vertebra and with all this's bad....and I know there's nothing you can do about that......and I know there is nothing a surgeon can do about it."
     "I'm not going to lie to you or feed you a line.  Besides, I'm sure you've done your homework as always,"
     I interrupted and chuckle, "Yeah, I've done my homework.  I know that surgery realistically has very little to offer me."
     The sadness in her eyes told me everything I needed to know, "I know.  I could send you to one if you want but you already know the're one of my youngest patients....on the outside you look great, but on the inside...your spine looks like an old man."
     I remembered back to when I first started down this road of pain with my family doc.  He took an x-ray and we counted an extra vertebra.  I recounted it to her, "I asked him if I am like this now, what am I going to look like when I'm in my 60s?  He said, let's not think about that right now."  She chuckled in agreement.  And we went so she could stick more needles into my spine.

May 10, 2016

my old life

I sometimes miss my old life.  Wait, let me be more precise with my words lest I get lost writing all the things I miss.  I sometimes my days in research.  A project of mine from years back that was shared with another group within the company was recently presented at an endocrinology conference.  It felt good for our data to be included as most of my work ended up going into patents rather than publications.  And in the biological sciences world, publications mean more when it comes to hiring time.  A full publication should be following soon.

PP30-2 Fads1 Knockout Mice Are Lean with Improved Glycemic Control and Decreased Development of Atheromatous Plaque

Program: Abstracts - Orals, Poster Previews, and Posters
Session: PP30-Regulation of Body Weight Via Adipose and Brain Poster Preview
Sunday, April 3, 2016: 11:30 AM-11:45 AM
Room 258 (BCEC)

Poster Board SUN 600
David R Powell*1, Jason P Gay1, Melinda Smith1, Nathaniel Wilganowski1, Angela Harris1, Autumn Holland1, Maricela Reyes1, Laura Kirkham1, Laura Kirkpatrick1, Brian Zambrowicz1, Gwenn M. Hansen2, Kenneth A Platt1, Isaac van Sligtenhorst1, Zhi-Ming Ding1 and Urvi Desai1
1Lexicon Pharmaceuticals, Inc., The Woodlands, TX, 2Lexicon Pharmaceuticals, The Woodlands, TX
Delta-5-desaturase (D5D) and D6D, encoded by the fatty acid desaturase 1 (FADS1) and FADS2 genes, respectively, are enzymes in the synthetic pathways for the omega-3, -6 and -9 polyunsaturated fatty acids (PUFAs).  Although PUFAs appear to play a role in mammalian metabolic pathways, the physiologic effect of isolated D5D deficiency on these pathways, and the potential value of inhibiting this enzyme to treat metabolic disorders, is not clear.  After generating >4,650 knockouts (KOs) of independent mouse genes and analyzing them in our high-throughput phenotypic screen, we found that Fads1 KO mice were among the leanest of 3,651 chow-fed KO lines analyzed for body composition by dual energy x-ray absorptiometry, and were among the most glucose tolerant of 2,489 high fat diet (HFD)-fed KO lines analyzed by oral glucose tolerance test (OGTT). In confirmatory studies, we used quantitative magnetic resonance spectroscopy to show that chow- or HFD-fed Fads1 KO mice were significantly leaner than wild type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 38% and 31% lower in Fads1 male and female KO mice, respectively (P < 0.001 for each). Fads1 KO mice also had significantly lower glucose (P < 0.01) and insulin (P < 0.001) excursions during OGTTs along with significantly lower fasting glucose (P < 0.05), insulin (P < 0.01), triglyceride (P < 0.05) and total cholesterol (P < 0.001) levels. In additional studies using a vascular injury model, Fads1 KO mice had significant 62% and 57% decreases in femoral artery intima/media ratio after 16 days of exposure to a copper-containing silicone vascular cuff (P < 0.01 for each independent experiment), consistent with a decreased inflammatory response in the arterial wall of Fads1 KO mice. Based on these results, we bred Fads1 KO and WT mice onto an ApoE KO background and fed them a western diet to create an atherogenic environment; after 14 weeks we collected the aortic tree of each mouse, stained it with Sudan IV to identify areas of atheromatous plaque, and found that the aortic trees of male and female Fads1 KO mice had 37% and 44% less plaque, respectively, than did those of their WT littermates (P < 0.05 for each). Importantly, 1) analysis of the arachidonic acid/dihomo-gamma-linolenic acid and the gamma-linolenic acid/linoleic acid ratios in brain and liver phospholipid fractions of Fads1 KO mice were consistent with the combination of markedly decreased D5D activity and normal D6D activity, respectively; and 2) our Fads1 KO mice did not appear to have decreased survival even on diets low in arachidonic acid.  We conclude that these Fads1 KO mice exhibited a beneficial metabolic phenotype, and that this beneficial phenotype suggests that selective D5D inhibitors may be useful in the treatment of human obesity, diabetes and atherosclerotic cardiovascular disease.