Mouse Model of Congenital Hydrocephalus

Congenital hydrocephalus continues to be a difficult disease to treat.  Unfortunately research which explains the exact mechanisms leading to the development of this disease is lacking, likely as a result of no robust models.

In 2011, Stottmann et al, were looking to find and understand the genes involved with neurodevelopment.  In a mouse model, their lab performed a forward genetic screen using ENU to produce novel mutations with the goal of modeling human genetic defects.  During the screen, they produced a mutation which they called “progressive hydrocephalus” (prh).  At birth, these mice appear normal, but at day 14 they are visibly hydrocephalic and do not survive to the weaning period. The image above shows how the mice look compared to wild type (wt) mice.

Recently our lab discovered a gene that is completely devoid in the prh mice called coiled-coil domain containing protein 39 (Ccdc39).  This gene was found to be richly expressed in cells containing cilia and was ultimately found to be required for the assembly of inner dynein arms for the normal ciliary motility in humans and dogs (Merveille et al.).  This is important because according to Lodish et al.:

the inner-arm dyneins are responsible for producing the sliding forces that are converted to bending; this suggests that inner-arm dyneins are essential for bending

Essentially, if the inner dynein of cilia are not assembled correctly, bending forces within the cilia cannot be generated which then would greatly affect motility of the cilia and thus it’s main function.

Our lab has preliminary data that suggests the prh mutation results in loss of ccdc39 protein within the choroid plexus, and this is what may be causing the hydrocephalus phenotype seen in prh mice.  Thus aims of our research include:

  1. Proving the ccdc39 mutation in prh mice is the cause of the hydrocephalus
  2. Then selectively knocking out the ccdc39 gene in the choroid plexus to prove that cilia disruption within the choroid plexus itself is responsible for the hydrocephalus phenotype seen in prh mice
  3. Show that CSF production is abnormal in choroid plexus cells of the ccdc39 mutants

I hope to gather enough data this year to accomplish each of these goals.  I am excited for this year in the lab and am thankful to Dr. Mangano and Dr. Goto for their mentorship.


References
  • Stottmann, R. W., Moran, J. L., Turbe-Doan, A., Driver, E., Kelley, M., & Beier, D. R. (2011). Focusing forward genetics: a tripartite ENU screen for neurodevelopmental mutations in the mouse. Genetics, 188(3), 615–624. http://doi.org/10.1534/genetics.111.126862
  • Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 19.4, Cilia and Flagella: Structure and Movement. Available from: http://www.ncbi.nlm.nih.gov/books/NBK21698/
  • Merveille, A.-C., Davis, E. E., Becker-Heck, A., Legendre, M., Amirav, I., Bataille, G., et al. (2011). CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nature Genetics, 43(1), 72–78. http://doi.org/10.1038/ng.726

Artifacts – Website

According to Google, and artifact is:

an object made by a human being, typically an item of cultural or historical interest

In this case, artifacts on my website have been projects that I find interesting, and are of historical interest to me, as they highlight my growth in projects.

In this inaugural edition of adding artifacts, I’d like to link to my previous websites in an effort to show the evolution of this website over the last 10+ years.

2006 – my first ePortfolio, built from HTML through Dreamweaver.  Hit the “Home” button up in the top right corner to enter the website.  Many of the links are broken, and the website requires flash to work properly.  Should you be using a browser that does not have FLASH installed, you will just see “missing plug-in” everywhere.

 

2008 – In all my experience from the first ePortfolio, I redesigned the entire website for a more modern look.  FLASH plug-ins are still required, but the website has a more refined look, and is an interesting snapshot of my life at this time just before medical school.

 

As I entered medical school, I was officially not a technology fellow any more.  So I had to decide, do I let the ePortfolio die, or do I continue it myself.  I felt that I couldn’t let my website die and stay behind with my undergraduate years.  I officially bought the domain “shawnvuong.com” and started building my third version of the website.  At this point, flash was no longer the standard of the internet.  CSS now becoming the norm.  This was a pivotal time for the website, going from a mandatory portion of my fellowship, to a professional marketing tool for my online persona.

First attempt – did not like the layout, and it was difficult to incorporate the photos.  I ultimately decided I wanted a layout with cleaner lines.

Second attempt – I liked this layout a lot better, but felt that there were too many boxes to fill.

Third time is a charm.  This ultimately became ShawnVuong.com in 2012.

 

Since I had the server space and the ability, I offered my services to others.

At one point my mother thought she was going to open a home-made soap business.  I drafted this as her potential website.  However, her business never came to fruition.

I also ran some websites while I was in medical school.  One was a philanthropy website for an AMA 5K organized by the medical school students.  Unfortunately, I was not able to continue upkeep for this website, and its been at a standstill since 2013.

Unfortunately there are a few other website projects that have been lost in the chaos of life, whether that be old failed hard drives or just lost in the pathway of life.

As I look through these websites, its cool to see the evolution of this site through the years, and hope to keep these available for the future by documenting them here as one of my first artifacts of the new website upgrade.

Update to ShawnVuong.com

Well the time has come to update ShawnVuong [dot] com.  I have been in residency for 4 years now, and have not had any time to update or write on the blog, but I have now entered my PGY-5 year and the time is now.  At the University of Cincinnati neurosurgery residency, the PGY-5 year is currently our “professional development” year.  This year I am working in the Mangano Lab at CCHMC.  I am very excited to be working out genetic mechanisms of congenital hydrocephalus.  As a result of being in the lab, I have significantly less clinical duties, which allows me to have time to update this site.

The overall look of the site has obviously changed drastically, but so has the actual build of the website.  All of my previous e-portfolio and website projects were created using Dreamweaver software, which required me to learn HTML, CSS, and PHP.  This is time consuming and can be onerous to update and format.  There were times when I was making the previous versions of the website that I found myself spending whole weekends trying to code an object to position itself in the browser, where I wanted it to be.  Given the amazing rate of increased technology and improved ease of website building over the last 4-5 years, I have come to appreciate the customization of WordPress.  As a result, this entire website rebuild only took a couple weeks with the help of WordPress.  I chose this platform because of my previous familiarity with the software, but also due to the ease of setup, the ability to quickly change an entire website’s look but updating a theme, and simplicity of adding posts and pages to keep the website updated.

I hope to post on the blog more often now, and hope you enjoy the new website!

When should an ICP monitor be removed in Severe TBI patients?

When should the neurosurgery team take out the ICP monitor after severe TBI?  One paper suggests that we should wait until after 7 days.  Up to 17% of patients have a delayed ICP rise after severe injury.  That is of course assuming that there is no exam or functional status marker to follow, as the authors mention in their discussion.

 

O’Phelan, K. H., Park, D., Efird, J. T., Johnson, K., Albano, M., Beniga, J., et al. (2009). Patterns of increased intracranial pressure after severe traumatic brain injury. Neurocritical Care, 10(3), 280–286. doi:10.1007/s12028-008-9183-7

What is the Chou Procedure?

A procedure used in neurosurgery in an attempt to save a cranioplasty flap after an infection. Paper by Dr. Chou in 1974 describes the procedure.

 

Open debridement. Placement of two channel drains (or 4). Placed superior and inferior in the subgaleal (or subgaleal and epidural).

 

Paper originally used 1 g of Keflin (cefalotin).  Irrigating solution is infused at a rate of 1-2 liters per 24 hours (40-80 mL/hr)  and continued for 5 days.

 

Nursing note: call if output is 10 mL or more different than input.

 

Reference:

Erickson, Seljeskog, and Chou. Suction-irrigation treatment of craniotomy infections. J neurosurgery. 1974 Aug; 41(2):265-7

Guidelines for Pre-operative Antibiotics for Neurosurgery

Antibiotic Doses:

Ancef = 2 grams or 3 grams if >120 kg (30mg/kg in kids) re-dose q4 hr

Clinda = 900mg (10mg/kg in kids) re-dose q6 hr

Vanc = 15mg/kg no re-dosing

*Vanc Dosing –

In a study of 2048 patients undergoing coronary bypass graft or valve replacement surgery receiving vancomycin prophylaxis, the rate of SSI was lowest in those patients in whom an infusion was started 16–60 minutes before surgical incision.

Overall Recommendation on Timing:

Overall, administration of the first dose of antimicrobial beginning within 60 minutes before surgical incision is recommended. Administration of vancomycin and fluoroquinolones should begin within 120 minutes before surgical incision because of the prolonged infusion times required for these drugs. Because these drugs have long half-lives, this early administration should not compromise serum levels of these agents during most surgical procedures.

Population Studies Reveal:

  • S. aureus nasal colonization in the general population decreased from 32.4% in 2001–02 to 28.6% in 2003– 04 (p < 0.01), whereas the prevalence of colonization with MRSA increased from 0.8% to 1.5% (p < 0.05)
  • Between 2007 and 2009, 23.3% of children were colonized with S. aureus, but the proportion of children colonized with MRSA had increased from 8.1% in 2004 to 15.1% in 2009.

Official Recommendation Guideline for Neurosurgery Procedures

A single dose of cefazolin is recommended for patients undergoing clean neurosurgical procedures, CSF-shunting procedures, or intrathecal pump placement (Table 2). Clindamycin or vancomycin should be reserved as an alternative agent for patients with a documented b-lactam allergy (vancomycin for MRSA-colonized patients). (Strength of evidence for prophylaxis = A.)

Official Recommendation Guideline for Spine Procedures

Antimicrobial prophylaxis is recommended for orthopedic spinal procedures with and without instrumentation. The recommended regimen is cefazolin (Table 2). (Strength of evidence for prophylaxis in orthopedic spinal procedures = A.) Clindamycin and vancomycin should be reserved as alternative agents as described in the Common Principles section. If there are surveillance data showing that gram-negative organisms are a cause of SSIs for the procedure, practitioners may consider combining clindamycin or vancomycin with another agent (cefazolin if the patient is not b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone if the patient is b-lactam allergic). Mupirocin should be given intranasally to all patients known to be colonized with S. aureus.

Clinical practice guidelines for antimicrobial prophylaxis in surgery. American Journal of Health-System Pharmacy, 2013 vol. 70 (3) pp. 195-283

Spinal Manipulation No Better Than Other Treatments for Acute Lower Back Pain

New evidence by the Cochrane Collaboration shows that spinal manipulation (or adjustments) are no better at treating acute (6 weeks or less) lower back pain, than over the counter ibuprofen or other NSAIDS.  In fact, the back pain resolves on its own in most cases.  Here is what the Cochrane Collaboration had to say about their findings:

Low-back pain is a common and disabling disorder, representing a great burden both to the individual and society. It often results in reduced quality of life, time lost from work, and substantial medical expense. Spinal manipulative therapy (SMT) is widely practised by a variety of healthcare professionals worldwide and is a common choice for the treatment of low-back pain. The effectiveness of this form of therapy for the management of acute low-back pain is, however, not without dispute.

For this review, acute low-back pain was defined as pain lasting less than six weeks. Only cases of low-back pain not caused by a known underlying condition, for example, infection, tumour, or fracture, were included. Also included were patients whose pain was predominantly in the lower back but may also have radiated (spread) into the buttocks and legs.

SMT is known as a ‘hands-on’ treatment directed towards the spine, which includes both manipulation and mobilization. The therapist applies manual mobilization by passively moving the spinal joints within the patient’s range of motion using slow, passive movements, beginning with a small range and gradually increasing to a larger range of motion. Manipulation is a passive technique whereby the therapist applies a specifically directed manual impulse, or thrust, to a joint at or near the end of the passive (or physiological) range of motion. This is often accompanied by an audible ‘crack’.

In this review, a total of 20 randomized controlled trials (RCTs) (representing 2674 participants) assessing the effects of SMT in patients with acute low-back pain were identified. Treatment was delivered by a variety of practitioners, including chiropractors, manual therapists, and osteopaths. Approximately one-third of the trials were considered to be of high methodological quality, meaning these studies provided a high level of confidence in the outcome of SMT.

Overall, we found generally low to very low quality evidence suggesting that SMT is no more effective in the treatment of patients with acute low-back pain than inert interventions, sham (or fake) SMT, or when added to another treatment such as standard medical care. SMT also appears to be no more effective than other recommended therapies. SMT appears to be safe when compared to other treatment options but other considerations include costs of care.

 

 

References:

http://www.aansneurosurgeon.org/2012/10/02/spinal-manipulation-no-better-than-other-treatments-for-acute-lower-back-pain/

http://summaries.cochrane.org/CD008880/spinal-manipulative-therapy-for-acute-low-back-pain

http://www.ncbi.nlm.nih.gov.proxy.libraries.uc.edu/pubmed/22972127

 

Bilateral Fixed and Dilated Pupils

                          

We all know that the dreaded bilateral fixed and dilated pupils is a sign of something bad after a traumatic event.  But how bad is it?   When you see this sign, what do you tell the family?  Will their son, daughter, husband, wife, father, mother, ever be the same?  Well doctor, how bad is it?

One study suggests that if a trauma patient who has bilateral fixed and dilated pupils on scene with a true GCS3, they have no real appreciable chance of survival. It would be wise to discuss comfort care measures at this point. Only 6 in this study survived and all of them had a GCS higher than 3 at some point in their care.

http://www.ncbi.nlm.nih.gov.proxy.libraries.uc.edu/pubmed?term=19070839