DBA Research Needs You

ATTN: DBA Parents and Patients

Ellen Muir

Some things to consider when having a port placed:

Always weigh the risks and the benefits of any medical intervention.    

A port is a small medical device placed under the skin and is used to infuse fluids for medical treatment into the blood stream and to also withdraw blood from a large vein.  It is accessed with a special needle, in usually one stick.  Its parts include a reservoir with a septum (area where the needle is inserted), and catheter.  The special needle used to access it is called a 'huber' needle.  It has a 90 degree bend so it is comfortable when in use and is 'non coring,' which means it won't leave a hole when the needle is removed.

A port may sometimes be referred to as a port-a-cath, mediport, or passport.  Depending on the manufacturer, the name varies.  Just as the name varies, so does the size and materials it is made of.  Most port reservoirs are made of stainless steel, titanium or plastic. For anyone who may need to have a cardiac MRI to look for iron overload, we recommend a plastic port so it does not interfere with the results.  If it cannot be plastic, placement outside the scanning field is recommended (such as right side of chest).  If your hospital does not use plastic ports, they can be special ordered.

The reservoir has a silicone septum which allows it to be punctured with a special needle, hundreds of times.  It is self sealing so it does not leak when the needle is taken out.  The catheter, which attaches to the reservoir, is made of a soft, bendable silicone or polyurethane.  The surgeon must make a pocket for the reservoir under the skin, usually in the chest area.  Speak to your surgeon to decide on what area is best for you.  Your options for placement are upper chest, over the ribs (under the breast), or sometimes in the forearm.  The catheter is then threaded through a major vein and ends at the superior vena cava of the heart.

Poor IV access when receiving monthly blood transfusion is one reason for placing any type of central venous access device (CVAD).  Other reasons may include for delivery of chemotherapy, IV nutrition, antibiotics and for dialysis.   A Broviac (Hickman, Groshong) is another type of CVAD, where the access point is outside of the body.  This type of 'tunneled catheter' is what is used during stem cell transplantation.  A peripherally inserted central catheter (PICC) is another type of external catheter that is used for temporary IV access. 

Benefits:

IV's can be started quickly and relatively easily without repeated needle sticks.  You can continue to bathe and even swim with a port once the surgical incision has healed.  A numbing cream can be placed to the port site 30 minutes before accessing it so you don't feel the pinch.

Some homecare agencies will not provide 24/7 Deferral therapy with an IV that is not a central line.  A port is a good option.

Possible Complications:

Infection - a severe bacterial infection can compromise the device, require its surgical removal, and seriously jeopardize the health.   To prevent infection, these ports are accessed using sterile technique, the needle should be changed once a week.  If you experience fever, you need to seek medical attention immediately, so blood cultures can be taken (sometimes from the port and from a vein in the arm).  Antibiotics need to be given through the port right away to prevent sepsis, a serious life threatening blood infection.

If receiving 24/7 IV therapy, the dressing must stay dry and needle be changed weekly to prevent any bacteria from growing.

Thrombosis - formation of a blood clot in the catheter may clog the port.  To prevent clotting, the port is flushed with saline and heparin, usually by a nurse or other medical professional, or someone properly trained that is a family member or the patient, at least once every four weeks, if not being used and after it is used for treatment or blood draw.

If a thrombin sheath forms at the tip of the catheter (forms a kind of flap) blood is not able to be withdrawn.  The catheter can still infuse as it the flap is pushed away with pressure of the fluid.  In the future, this may become a complete blockage or be a source of infection.

Mechanical failure- sometimes when withdrawing blood the tip of the catheter is pulled against the wall of the vein and no blood is able to be withdrawn, due to too much suction.  The catheter can still infuse as it is pushed away from the vein wall with the pressure of the fluid.

Infiltration- if the needle is not placed through the port septum, fluid can leak and cause pain, swelling and sometimes redness.

Age - If the device is put into a child, the child's growth means that the catheter becomes relatively shorter and will move further away from the superiorvena cava - it may be necessary to remove or replace it.

Complications can occur during surgery, speak to your surgeon and anesthesiologist.

If you are trying to decide which port is right for your needs, you can contact me and I can help guide you on a more personal level.

Ellen Muir, RN, MSN, CNS                                                             877-DBA-NURSe (322-6877)                                                   emuir@nshs.edu

Steven R. Ellis, PhD DBAF Research Director

Reciprocal space!

 No, not as in the "final frontier"- type of space, but instead the type of space those individuals trying to determine the three dimensional structure of biological macromolecules find themselves in. 

A way of determining the structure of a molecule too small to see is to first form solid crystals of these molecules, and then bombard these crystals with directed X-rays and measure how the molecules within the crystals diffract the X-rays.  The reflections collected from the diffracted X-rays provide information about electron densities within a structure and bond distances between atoms.  Using this information, and tens of thousands of calculations, it is possible to deduce the structure of many types of molecules that are medically relevant.  The reference to reciprocal space relates to the fact that there is an inverse relationship between bond distances between atoms in the structure and the angle in which the X-rays diffract.  Consequently, when you measure the reflections produced from diffracted X-rays, larger reflections equate to smaller molecular units and vice versa......go figure.    

X-ray diffraction was developed in the early 1900's by William Lawrence Bragg where it was first used to determine the structures of relatively small molecules.  As the technology increased, it became possible to determine the structure of increasingly large structures culminating with the solution of the first three-dimensional structure of a protein in the 1950's by Max Perutz and John Kendrew.  The protein was myoglobin, a relatively small oxygen binding protein isolated from the muscle of sperm whales.  Since this time the structures of hundreds, if not thousands of different proteins, have been solved.

By now you might be scratching your head wondering where I am going with this discourse.  Well, around the turn of the millennium the three dimensional structure of a small ribosomal subunit was solved ¹, followed shortly by the structure of the large subunit ², and then both subunits joined as the ribosome itself ³.  As impressive as these feats were, they were of somewhat limited value for those of us working in the DBA field because these structures were for bacterial ribosomes, and the majority of DBA genes encode ribosomal proteins that are not found on the bacterial ribosome.  Instead, many of the ribosomal proteins affected in DBA appear to be bells and whistles added to the basic structure of the bacterial ribosome as more sophisticated organisms including us, evolved.     

All this brings me to this month's Journal Club and a manuscript published in the journal, Science, reporting the three dimensional structure of the yeast ribosome, which for all intents and purposes of this Journal Club is much like our own4.  Fortunately, the journal Science allows their figures to be reproduced for educational purposes, so I can show you the structure of the ribosome deduced by Ben-Shem and colleagues in the attached document.  Just to give you a feel for what went into solving this structure, the researchers had to pinpoint approximately 13,000 amino acid residues comprising the 80 ribosomal proteins and over 5,500 nucleotides that make up the 4 ribosomal RNAs, all I might add while working in reciprocal space. 

What this structure provides is the precise location on the ribosome of the known ribosomal proteins encoded by DBA genes.  While this information is gratifying, one could reasonably ask whether it illuminates why the loss of these proteins causes DBA.  Not really, at least not to me in the limited time I have had so far to peer into this remarkable structure.  But alas, I am just one person, and while I may know a little bit more about ribosomes that the average person on the street, there are a lot of outstanding ribosomologists around the world, anyone of which may look at this structure and derive a key insight that may push the DBA field to the next level. 

Speaking of ribosomologists, it just so happens that there will be a world-wide gathering of these specialists in August of 2012 at the tri-annual Ribosome Synthesis meeting to be held in Banff, Alberta.  Moreover, Marat Yusupov who led the group that solved the yeast ribosome structure will be one of the plenary speakers at this conference.  This meeting will also have a second plenary speaker who is non-other than our own Dr. Jeffrey Lipton.  Dr. Lipton as you might expect will be speaking on ribosomes and disease, with DBA no doubt prominently featured in this talk.  Further, I should mention that the DBA Foundation has pledged financial support for this meeting further increasing DBA visibility within the greater ribosome community.

Traditionally, the ribosome synthesis meeting is attended by some pretty hard core ribosome types you probably wouldn't want to meet in a dark alley.  But in recent years more and more hematologists have begun to infiltrate this meeting, reaching the point this year where ribosomes and disease has become a major focus of the meeting.  So, last Journal Club I wrote about how some of the leading hematologists in the world are thinking about ribosomes with this month's Journal Club holding the promise of another reciprocal relationship with some of the leading ribosomologists in the world puzzling over hematology. 

1.            Wimberly BT, Brodersen DE, Clemons WM, Jr., et al. Structure of the 30S ribosomal subunit. Nature. 2000;407(6802):327-339. Prepublished on 2000/10/03 as DOI 10.1038/35030006.

2.            Ban N, Nissen P, Hansen J, Moore PB, Steitz TA. The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science. 2000;289(5481):905-920. Prepublished on 2000/08/11 as DOI.

3.            Yusupov MM, Yusupova GZ, Baucom A, et al. Crystal structure of the ribosome at 5.5 A resolution. Science. 2001;292(5518):883-896. Prepublished on 2001/04/03 as DOI 10.1126/science.1060089.

4.            Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. The structure of the eukaryotic ribosome at 3.0 A resolution. Science. 2011;334(6062):1524-1529. Prepublished on 2011/11/19 as DOI 10.1126/science.1212642.