by George Taniwaki

A new organ preservation method may help increase the number of transplants. It could dramatically increase the survival of patients with end stage liver or heart disease.

Background

The most common organ to be transplanted are kidneys. Part of the reason is that there are lots of patients with kidney failure waiting for a transplant. And part of the reason for that is patients with kidney failure can be placed on dialysis therapy while waiting for a donor organ. This allows them to survive several years while waiting for a donor organ. Patients requiring a replacement for failed hearts, lungs, and livers cannot wait. They must be transplanted quickly. If an organ is not available, they will die.

The other reason kidneys are the most common organ to be transplanted is that donor kidneys can be kept in ice water storage for 24 to 36 hours prior to transplant and still remain viable. This provides time to run crossmatch tests using blood samples from the donor and several possible recipients, contact the best matching patients and their surgeons, get them to the hospital, and transport the donor organ to the hospital. Hearts can only be stored about 4 hours and livers can only be stored about 12 hours. This often is not enough time to prepare for surgery and so the donor organ has to be discarded, unused.

I discuss some of these issues in earlier blog posts. For instance, see my Nov 2010 blog entry and May 2010 blog entry.

New and supercool protocol

In a paper published in Nature Medicine, Jun 2014 (subscription required), Tim Berendsen at University Medical Center in Utrecht, the Netherlands, Bote Bruinsma at Massachusetts General Hospital and Harvard Medical School, and others have developed a new protocol to supercool organs below zero (32 deg F) without freezing them. Their technique was tested on rat livers, but would likely work on human livers and would work with other organs, including kidneys. A good explanation of the process is included in a Jun 2014 press release.

HarvardRatLiver

Figure 1. Supercooled rat liver being perfused with new solution developed by Harvard researchers. Photo from Harvard University

Their technique involves four steps. First, the organ is placed in a vessel while an ice cold solution (usu. about 4 deg C, 39 deg F) is circulated through it, a process called perfusion. The solution contains dissolved oxygen and nutrients such as glucose that help keep the organ alive. This is already the standard procedure for perfusing organs.

What is new, is the perfusion solution and the next steps. The perfusion solution contains PEG-35kD (polyethylene glycol) and other proprietary ingredients (to be commercialized) that act as an antifreeze. This allows the solution and the liver to be carefully cooled to -6 deg C (21 deg F) in a way that avoids the formation of ice crystals that could damage the cells in the liver. The liver can remain perfused in the supercooled condition for up three days and remain viable. Then the liver is carefully warmed to above freezing and prepared for surgery as normal.

HarvardRatLiverChart

Figure 2. Chart showing temperature profile of liver using proprietary perfusion solution and supercooling protocol. Image from Nature Medicine

Extending the viable time for liver transplant from 12 hours to three days would be a huge change. It would allow many more transplants to occur, with a corresponding decrease in the number of patient deaths caused by a shortage of organs. Just as important, by allowing time for multiple crossmatch tests to be conducted, it could potentially improve the matching of organs to patients.

The next steps in the research is to try livers from larger animals and to test the protocol on other organs.

by George Taniwaki

About comment spam

Comment spam is a real problem. Most websites that allow comments (like mine) receive over 100 spam messages that link to unethical or fraudulent websites for each legitimate comment they receive.

Luckily, there are excellent spam filters that identify and remove these annoying click-bait messages. For instance, the service that hosts this blog, WordPress, uses a service called Akismet. These spam filters use pattern recognition to find suspicious messages based on characteristics like message content, sender email address, sender IP address, web page commented on, etc. Suspect messages are tagged as spam and moved to a junk comment folder.

Naturally, in the spam arms race, the creators of spam campaigns need tools to rapidly create comments, ideally a unique one for every blog post, so as to avoid being detected.

The message

I recently received a comment on this blog that reveals how comment spammers create messages. The comment was actually not the intended comment. Rather, the spammer sent me over 300 lines of code they used to create custom-looking comments. Phrases that could be customized were enclosed in curly braces {}. The options for the words in a phrase were separated by vertical pipes |. The curly braces could be nested to allow multiple levels of customization. In fact, the entire comment starts with a curly brace so that different versions of the message could be sent. The spam message generator is partially reproduced below.

Note in particular how many of the characters (highlighted in yellow) are accented or Unicode homoglyphs, meaning they form words that look like English, but will not appear in any dictionary that might be used by a spam filter to detect phrases often used in spam messages. Of special note is that words used multiple times will often have a different glyph replacement in each instance.

{

{ӏ have|I’ve} bеen {surfing|browsing} online mοrе thаn {three|3|2|4} hours todaу, ƴet I
never found any іnteresting article like
yours. {It’s|It іs} pretty worth enoսgh for me. {Іn mу opinion|Personally|In my view}, іf
ɑll {webmasters|site owners|website owners|web owners} аnd
bloggers mаde gooԁ content as ƴou dіd, tҺe {internet|net|web} will bе {much moгe|a lot more} useful than ever beforе.|
I {couldn’t|could not} {resist|refrain fгom} commenting.

{Very wеll|Perfectly|Well|Exceptionally well} written!|
{ӏ wіll|І’ll} {rіght awaʏ|immeԀiately} {tɑke
hold of|grab|clutch|grasp|seize|snatch} уoսr {rss|rss feed} ɑs I {can not|ϲаn’t} {іn finding|fіnd|to find} yοur {email|е-mail} subscription {link|hyperlink} օr
{newsletter|e-newsletter} service. Ɗo {yoս ɦave|yoս’ve} any?
{Please|Kindly} {аllow|permit|lеt} me {realize|recognize|understand|recognise|кnow}
{sߋ tɦat|in orԁer that} I {may juѕt|may|cοuld} subscribe.
Ҭhanks.|

The string of faux-fawning gibberish continues for another 290 lines or so and finally ends with this heart-felt closing.

Thɑnks fоr {greɑt|wonderful|fantastic|magnificent|excellent} {іnformation|info} ӏ wɑs looking for thіs {informatіon|info} for my mission.|
{Hi|Hello}, i tɦink that і saw you visited my {blog|weblog|website|web site|site} {ѕo|thus}
i сame to “return the favor”.{I аm|I’m} {trying to|attempting tߋ} find thіngs to {improve|enhance}
mʏ {website|site|web site}!І suppose its ok to use {some of|a fеw of} уօur ideas!\

I’m somewhat surprised the code above can confuse a spam filter. A pattern recognition algorithm could be designed to detect which forms of phrases, misspellings, and glyph substitutions are most commonly seen in spam rather than in messages typed by honest but error-prone humans.

Anyway, I want to thank this incompetent spammer for providing me with content for this blog post. And of course, thanks for the {kind|wonderful|supporting} message.

For examples of actual blog spam that prey on people who might be persuaded to sell a kidney, see this previous blog post.

by George Taniwaki

I recently received two comments on this blog from what appear to be scam artists seeking to prey on desperate people who might be persuaded to buy or sell a kidney.

I didn’t bother to follow up with either person to learn more about this scam. I say scam because it is illegal to buy or sell organs in nearly every country on earth. Further, nobody will pay for your travel expenses to a developing nation to have a nephrectomy (kidney removal surgery).

Bottom line: Do not respond to messages from strangers offering you money!

The messages

The first message shown below, is short and specifically is targeted at poor people who need money.

Do you want to sell your kidney due to financial problem? If yes you are in the right place of selling your kidney for good money. contact us @ SAWAN NEELU ANGEL’s HOSPITAL Multi specialist Home, J-293,Saket, New Delhi-17 India.. Email Us now:

Very Urgent

 

Dr Ashok kumar
ASN Directo

 

The second message is a bit of a mixed bag. This scam artist starts his pitch with an offer to help poor people desperate for a chance to escape debt. But at the end of his message, makes a stab at conning kidney patients to make a down payment for a transplant.

Good day,

Do you want to buy a Kidney or you want to sell your kidney? Are you seeking for an opportunity to sell your kidney for money due to financial break down and you don’t know what to do, then contact us today and we shall offer you good amount for your Kidney. My name is Doctor Calvin Cien am a Nephrologist in UBTH clinic hospital. Our clinic is specialized in Kidney Surgery and we also deal with buying and transplantation of kidneys with a living an corresponding donor. We are located in Indian, Turkey, Nigeria, USA, Malaysia. If you are interested in selling or buying kidney’s please don’t hesitate to contact us via email.

Best Regards.
Dr. Calvin Cien.

 

For more on how comment spam is created, see this blog post:

Comment spam template (June 2014)

For more on how scams work, see the following blog posts:

The Craigslist counterfeit check scam (June 2013)

Paris scam artists (March 2011)

by George Taniwaki

The human cytomegalovirus (CMV), a member of the Herpesvirus genus, is highly contagious and quite widespread. It is estimated that over two-thirds of all adults have anti-CMV antibodies in their blood and the proportion of the population exposed increases with age.

CMV infection is usually quite mild. Most people who have it don’t even know it. However, it can cause serious illness and death to those who are immunocompromised such as infants, the elderly, patients with HIV infection, and patients who have received a bone marrow or organ transplant. An excellent primer on CMV and its impact on kidney transplants in provided in the J. Amer. Soc. Nephr. Apr 2001.

Because CMV is so common, it is impossible (both mathematically and ethically) to avoid using donor kidneys that are infected, even when transplanting into a patient who tests negative for CMV antibodies.

As can be seen in the table below, the infection risk is lower for patients who test negative for CMV antibodies (possibly because they have a natural immunity to the virus). It is also lower for patients who receive a kidney from a donor who tests negative (since the kidney is less likely to carry the virus). The percentages in each group assumes random distribution of CMV among donor and patient populations.

Level of risk and (% of population) Patient CMV-
Lower risk  (33%)
Patient CMV+
Higher risk (67%)
Donor CMV-
Lower risk (33%)
Lowest risk (11%) Low risk (22%)
Donor CMV+
Higher risk (67%)
High risk (22%) Highest risk (45%)

 

For solid organ transplant recipients, CMV is the most common serious viral infection. Medscape notes that, “CMV infection usually develops during the first few months after transplantation and is associated with clinical infectious disease (e.g., fever, pneumonia, GI ulcers, hepatitis) and acute and/or chronic graft injury and dysfunction.”

The standard procedure to prevent or treat CMV infection is to prescribe ganciclovir, sold under the trade names Cytovene and Cymevene (Roche). Like other antiviral drugs, ganciclovir disrupts the replication of viral DNA.

Unfortunately, this drug has several limitations. First, widespread use of the drug seems to be leading to increased incidence of ganciclovir-resistant CMV infection. Second, the drug can cause serious side effects including hematological (blood) effects such as granulocytopenia (low white blood count), neutropenia (low neutrophil count), anemia (low red blood count), and thrombocytopenia (low platelet count). Third, animal studies showed it to be a potential human carcinogen, teratogen, and mutagen.

image

Figure 1. Replication of long chain of viral DNA by CMV. Image from New Engl. J. Med.

New therapy option

A new drug to prevent or treat CMV called letermovir is currently under investigation. In the New Engl J. Med. May 2014 (subscription required), Roy Chemaly and his coauthors report that among patients receiving hematopoietic stem-cell transplants (bone marrow transplants), use of letermovir significantly reduced the incidence of CMV infection and the level of viral DNA fell as the dose increased. This means the new drug is quite effective. Just as important, it had an acceptable safety profile. Patient taking even the highest dosage  did not report greater side effects than those taking the placebo. Specifically, it showed no hematologic toxicity or nephrotoxicity (kidney damage). An excellent discussion of this breakthrough is provided in an accompanying editorial that appears in the same issue. The editorial also highlights the higher reliability and sensitivity of quantitative polymerase chain reaction (PCR) to measure viral load and predict the onset of symptoms.

Naturally, additional studies will need to be conducted to test letermovir with patients receiving a solid organ transplant. But the initial test results are promising and give hope that within this decade fewer kidney transplant patients will lose their graft or their life due to CMV infection.

by George Taniwaki

This is a continuation of my class notes from Landscaping in the Northwest without the Need for Automatic Sprinklers, taught by noted local plant writer and speaker Marianne Binetti and sponsored by the Cascade Water Alliance.

Part 1 of this blog entry is posted in April 2014.

LandscapeNote05

Plants mentioned on page 5, Gold band yucca, Miss Willmott’s ghost, Blue fescue, Allium

LandscapeNote06

Plants mentioned on page 6, Smoke tree, Golden ninebark, Huckleberry, Elderberry, Salmonberry

LandscapeNote07

Plants mentioned on page 7, Rosemary, Sedum razzleberry

LandscapeNote08

Plants mentioned on page 8, Sword fern, Sedum autumnjoy, Euphorbia

LandscapeNote09

Plants mentioned on page 9, Begonia, Hen and chicks, Sempervivum glabifolium, Sedum angelina, Woolly thyme, Sandwort, Moss lawn, Blue star creeper

LandscapeNote10

Plants mentioned on page 10, Sedum echeverias, Creeping jenny, Christmas rose

Note: The hyperlinks to nurseries and garden shops in this blog post were added by me and are for reference only. They were not part of the lecture and are not meant as endorsements by me or the instructor.

by George Taniwaki

Last Saturday, I attended a free class sponsored by the Cascade Water Alliance, an association of several water districts in Western Washington. The class, entitled Landscaping in the Northwest without the Need for Automatic Sprinklers, was held in Sammamish, an eastern suburb of Seattle. It was taught by noted local plant writer and speaker Marianne Binetti. It was a great class and I learned a lot. Probably the most important thing I learned was to not be intimidated by plant names. There are thousands of varieties of ornamental plants and you can’t know them all. Just go to the nursery with a plan to buy water-conserving plants, ask for help, and pick things you like.

MarrianeBinetti

Marianne Binetti. Photo by Joe B

Ironically, it is raining today. But I know that come summer, the Puget Sound region will have three dry months. Our house has a big yard and out in the suburbs water is very expensive. I want to learn how to design and build a low maintenance/low irrigation landscape for our yard. And you can’t beat the price of a free class.

My wife Sue and I attended a similar class back when we lived in Denver. That class featured a technique called xeriscaping and was taught by the Denver Water Department. Denver is much drier than Seattle (15-inches rain per year in Denver vs. 38 inches in Seattle). However, we had a city house with a tiny yard plus water was much cheaper due to the senior water rights held by the city.

Both the Denver low-water xeriscaping class and Saturday’s no-water class covered how to choose drought-tolerant and freeze-tolerant plants like succulents, hardy perennials, and prairie grasses. These plants are not necessarily native to the respective regions, but will grow there and look appealing. Both classes also offered information on proper soil amendment, and mulching to minimize or eliminate the need for irrigation.

Enough description about the classes. Below are the notes I took during Ms. Benetti’s lecture. I took the notes on a 6-inch square notebook I received from Northwest Kidney Centers using a pen with black ink. I cut the pages out of the book, added the colors using felt-tip highlighter pens, and scanned the pages. Enjoy!

LandscapeNote01

Plants mentioned on page 1, Heavenly bamboo, Japanese red pine

LandscapeNote02

Plants mentioned on page 2, Wisteria, Clematis

LandscapeNote03

Plants mentioned on page 3, Barberry, Euonymous, Lavender, Spiraea

LandscapeNote04

Plants mentioned on page 4, Kinnick kinnick, Rock rose, Potentilla

Part 2 of this blog entry is posted in April 2014.

Note: The hyperlinks to nurseries and garden shops in this blog post were added by me and are for reference only. They were not part of the lecture and are not meant as endorsements by me or the instructor.

by George Taniwaki

It was raining all day, keeping me from doing yard work this afternoon. That’s my excuse and I’m sticking to it. So I started doodling and came up with an invention to keep exterior concrete steps from getting covered with puddles of water.

My idea is to use a hard rubber mold on top of each tread to cut notches in the step that act as gutters to guide the water down to the next step down.

The drawing below shows the cross-section of a typical concrete step with a 11-inch tread and 7-inch riser. The tread has a series of 1-inch wide triangular grooves molded into it. The grooves are sloped down the tread. The groove is 1/8-inch deep at the start of the tread (cross-section AA) and reaches 1/2-inch deep (to become 45-degrees) at the end of the tread (cross-section BB).

The design has several nice features.

  1. Unlike most concrete steps, the treads are not sloped. The tops of the grooves are level to the ground. This improves safety. You won’t slide, and potentially fall, when the steps are wet, muddy, or icy
  2. The grooves shed water from the treads. This keeps water from forming puddles on the treads even if the concrete for the steps is poured slightly off-level
  3. The grooves reduces the contact area between the step and your shoes, to increase traction, which again improves safety

ConcreteSteps

Concrete steps design. Drawing by George Taniwaki

I’ve never seen concrete steps with grooves like this. So either I am the first person to think of this, or my design is a solution in search of a problem that doesn’t exist.