Perfect Aim

...all over themselves!

Why is it that when children acquire a stomach flu virus that they inevitably come down with it as O-dark hundred and promptly puke in their beds and all over themselves? Inquiring minds want to know. Is it murphy's law or something?

Yes, you guessed right. The power of the pukiness has returned to the B family household. Yes, we won the stomach flu dance off and have one-by-one sent our girls to the vomitorium starting with Kesa, who passed it to Meghan, who passed it to Grace, who passed it to...hopefully not me or my dear husband. I'd like to boil myself right about now. Ewww!

Thankfully, Kesa is old enough to take care of business by herself, but our 5 and 3 year olds haven't yet.

Fun times at "party bug" central!

Alpha-1 Video

This showed up on my Google feed today. Cool! The author of the video says this about the video:

"stylized (and not too biologically correct) representation of the genetic disease alpha 1 antitrypsin deficiency"

Click twice on the movie to play it.

Liver Heal Thy Self

Source: http://www.sciam.com/article.cfm?articleID=9F4CE513-E7F2-99DF-3B827D53632DD53C&chanID=sa003

March 29, 2007 (Scientific American)

Gene Activates Liver Repair

Hunting for a way to let the liver heal itself without causing more harm than good
By JR Minkel

Researchers may have identified a master switch that activates the liver's ability to heal itself, suggesting a route to better treatments for liver diseases such as hepatitis and cirrhosis. Mice that lacked the gene showed a marked deterioration in their livers and lived shorter lives than normal mice.

Damage to the liver activates a group of specialized wound-healers called hepatic stellate cells (HSCs), which churn out scaffoldlike collagen fibers that support the growth of new liver cells. "You want the cells to get activated but you don't want them to stay activated for too long," says neurobiologist Katerina Akassoglou of the University of California, San Diego, because the fibers begin substituting for healthy liver tissue, leading to liver failure in people with chronic cirrhosis, for example. But researchers do not know which genes control the process.

Akassoglou and her colleagues thought they had a good candidate in the gene for the p75 neurotrophin receptor (p75NTR), a regulator of cell death in the brain that also switches on soon after liver injuries. Using mice that had a propensity for liver disease, her team created a strain of rodents that lacked the p75NTR gene. The livers of the engineered mice were covered in lesions after 10 weeks, and only half of the animals lived longer than that, compared with more than six months for the unmodified rodents.

The p75NTR protein sits on the surface of HSCs. The group believes that when activated by a still-unknown agent after liver damage, it stimulates a cascade of signals inside the cells that trigger them to begin the healing process, according to results presented in this week's Science. The next step, Akassoglou says, is to determine the role p75NTR plays in later stages of liver disease, to see if shutting it down will stop the harmful production of collagen.

"If you know what the switch is," she says, "and if you know how these cells become quiescent again … then you can start interfering with this process."

Another Birthday Girl

Today is my step-daughter, Kesa's, birthday. Happy 15th Kesa! I'm having a hard time believing it was so long ago that she came into my life. Time certainly does seem to speed up when you are observing a child grow up.

In a fitting tribute, I thought it worthwhile to share one of my more vivid memories of Kesa as a baby.

Kesa was crawling age. I think about 9 months old, but my memory is fading. At that time, her blond curls sprung up off her head and her cherubic cheeks glowed with a pink hue. I remember being shocked by how much she looked like Charlie.

As her chubby thighs and knees pushed against the brown carpet, she giggled and shrieked with joy as she approached me sitting on a sofa. I couldn't help but smile at her excitement. Charlie egged her on with "Come to Dada! Come to Dada!" Kesa squealed with delight and swiftly crawled about 6 feet toward us.

Charlie scooped her up, and that was when I first really witnessed the father-daughter bond between them. He kissed her cheek a bunch of times, and then put her down on the floor again. Kesa giggled again, and promptly crawled off toward her Papa. I knew Charlie was proud, but he exuded pride and parental love that day. I hope my memory of that day pays tribute to Charlie and Kesa's relationship.

Has it really been 15 years?

As Kesa prepares to learn how to drive, becomes more interested in boys, and works her way through high school, I see Charlie's bond continuing to deepen. He aches to talk to her on the phone or get an email from his busy teenager these days. (Kesa lives 4 hours away from us.)

I guess it makes me appreciate what we have with Grace and Meghan even more. They, too, will grow up too fast, and I had better appreciate them as little girls while I can.

Happy Birthday Kesa!

Magnesium Sulfate Protects Preemies?

I received mag with both Grace and Meghan while I was still pregnant. Hmmmm...

Magnesium sulfate may protect very preterm infants from brain injury

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=1319047&contentType=sentryarticle&channelID=30

Reuters Health - Apr. 17, 2007

NEW YORK (Reuters Health) - Magnesium sulfate given before very preterm birth may protect infants against brain injury without harming the mother, according to a report in the March issue of BJOG: An International Journal of Obstetrics and Gynecology. However, the benefit is not strong enough to recommend widespread adoption of the strategy.

Several reports have suggested that prenatal administration of magnesium sulfate for tocolysis or preeclampsia is associated with lower neonatal mortality and lower risk of cerebral palsy in very-low-birth-weight children, the authors explain.

Dr. Stephane Marret from Rouen University Hospital, France and associates investigated whether a single infusion of magnesium sulfate to women at risk of very preterm delivery would prevent neonatal mortality and/or white matter injury.

Slightly more women treated with magnesium sulfate (53.9%) had prolonged prelabor rupture of membranes (PPROM) than women who received placebo (46.6%), the authors report, but otherwise the groups had similar maternal and pregnancy characteristics.

There were no major maternal adverse effects among women treated with magnesium sulfate, the results indicate, and labor and delivery outcomes were similar for the two groups. Women in the magnesium sulfate group did, however, have a significantly higher rate of maternal-fetal infections.

Total neonatal mortality before hospital discharge, severe white matter injury, and the combination of the two were lower for the magnesium sulfate group, the researchers note, but the differences did not reach statistical significance.

Secondary cranial ultrasound outcomes also did not differ significantly among the 665 infants with available data, the report indicates, although the rate of all white matter injury and the rate of nonparenchymal hemorrhages were lower in the magnesium sulfate group than in the placebo group.

"The lack of a significant magnesium sulfate effect ... may be explained by the higher frequencies of PPROM and/or maternal-fetal infection observed in our magnesium sulfate group that may have counterbalanced the neuroprotective effect of magnesium," the investigators say.

"Our findings suggest a neuroprotective effect of magnesium sulfate given before very-preterm birth but do not provide strong enough evidence for recommending widespread magnesium sulfate use in clinical practice," Dr. Marret and colleagues conclude.

BJOG 2007;114:310-318.

The Birthday Girl

Five years ago today, a tiny, fussy wrinkled baby girl came abruptly out of my stomach. She had been delivered by c-section by Dr. Schultz because I had severe preeclampsia. I remember her cries that were as if to say, "Put me back in there! I'm not ready to be born yet." My thoughts were very similar, but I was so very sick and relieved that my baby was alive and getting the important care she needed in our experienced NICU.

That day, I became a mother...a mom who felt an amazing amount of love. A love that I had never felt before. A love that I can't describe appropriately in words. It is a love to be experienced not written about. I'm quite certain the mothers who read this will agree.

That day, a force to be reckoned with was born. Her name is Grace Ann. My beautiful girl. Our gorgeous daughter. An extension of both myself and my husband.

Today, we celebrate Gracie.

We celebrate Grace's endless spinning, jumping, laughing, running, teasing, whining, giggling, silly self.

We celebrate her inner beauty. Her need to declare her love at random times. Her intense need to stroke her ears and anything remotely soft or silky. Her moments of shrieking as Meghan calls her stinker pooper head. Her neverending movement as we sit as a family at the dinner table. Her intense dread at the prospect of getting cold or chilly. Her need for at least 12-13 hours of sleep per day. Her grouchy self in the morning. Her ramming speed approach to all things. Her hugs which allow you to feel the depths of her soul.

We celebrate all of Grace. We celebrate her past, present, and future.

Plus, we celebrate all of these beautiful 5 year old faces, which continue to deepen our love for her.

Happy Birthday Gracie. We love you forever.

Boston Marathon

On Grace's birthday, we are honored that a member of the American Liver Foundation's Run for Research Team in the Boston Marathon will be running in honor of Grace & Meghan. The girls were matched with our runner, Jen. This is her 4th year running. WOW! I can't even run 4 blocks.

Please consider donating to Jen's fundraising effort:

http://www.active.com/donate/liverteam07/JDavis297

We're proud that Jen runs to help cure liver disease and Alpha-1 is one of those diseases.

Jen, Gracie and Meghan are very proud of you.

ELBW Research

That is extremely low birth weight (ELBW) for those of you who haven't had micropreemies. Meghan qualified for this birth weight and as such qualifies for a myriad of additional risk factors for which Gracie would not be at risk.

I'm still reading this blog post, and need time to absorb and reflect before I showcase my opinion here.

Needless to say, Meghan, while still very much alive and with us, may have life challenges because of her very early birth.

http://talesfromthewomb.blogspot.com/2007/03/objectivity-in-long-term-neonatal.html
Jen

Preeclampsia and Future Cardiovascular Risk

7/10/2007: I'm not sure why but I've gotten at least 30 hits on this post in the last few days. A lot of people are being referred to this post via their email accounts. Anyone care to share what is so interesting about this post? As a survivor of preeclampsia, I'd love to hear what brings you here. Leave a comment please. :) Jen

More bad news for me as a two time severe preeclampsia survivor who developed hypertension after the birth of my 2nd daughter. Guess I'd better see what my internist thinks about this...

1: Expert Rev Cardiovasc Ther. 2007 Mar;5(2):283-94. Links
Preeclampsia and future cardiovascular risk.Newstead J, von Dadelszen P, Magee LA.
University of Saskatchewan, Department of Medicine, Saskatoon, SK, Canada. jill.newstead@shaw.ca

Pregnancy is a metabolic and vascular 'stress test' for women and those who 'fail' are at increased risk of long-term cardiovascular complications. Specifically, women who develop preeclampsia (and/or other manifestations of placental dysfunction) are at increased risk of coronary heart disease, stroke and cardiovascular disease in general. The risk is highest among women who develop both maternal (e.g., hypertension and proteinuria) and fetal (e.g., intrauterine growth restriction) manifestations of abnormal placentation, especially with preterm delivery. Most women who develop a maternal placental syndrome return to a normal clinical state in the weeks following pregnancy and their absolute risk of cardiovascular disease in the short term is very low. However, perhaps having a placentally complicated pregnancy affords women the opportunity to personalize risk and take action. Action is needed. The fact that we, as a population, are getting heavier and more sedentary is an urgent public health issue. The American Heart Association recommends that all women (even those at low cardiovascular risk) pursue dietary and lifestyle changes, in addition to smoking cessation. Engaging women of child-bearing age who may be motivated by a complicated pregnancy would be very valuable, from a public health perspective, given the prevalence and importance of cardiovascular disease in women, and the central role of the woman as caregiver to children, spouses and other family members.

PMID: 17338672 [PubMed - in process]

Seeing is Believing

Cross posting my entry on Preeclampsia Survivors:

http://preeclampsiasurvivors.blogspot.com/2007/03/seeing-is-believing.html

"This Close"

It has been a hard week for some of my online friends. Amanda from Imagine Bright Futures informed all of us at Liver Families that she had been diagnosed with breast cancer. It just seems like cruel irony that Amanda has to endure cancer along with her niece's biliary atresia. I will be praying for her as she undergoes a mastectomy on the 29th.

Then, I began reading heartbreaking posts from my pal, Sheri, whose son Antonio was critically ill. He had a liver transplant, but then developed Posttransplantation Lymphoproliferative Disorder (PTLD), which is a form of cancer caused by exposure to the Epstein-Barr Virus (EBV). It can happen in children who are immunosuppressed due to organ transplantation. After reading about Sheri's elation that Antonio had been given his life-saving gift of life, it seemed nearly impossible that she would be again watching her son slowly fade, and actually come "this close" when he had to fight pnuemonia on top of the PTLD.

Thankfully, Antonio has made marked improvement. Sheri has been away from her other three children for nearly a month, and like a God send, Kim, another Liver Families mom flew up from Texas to comfort Sheri. I think Kim's positive energy played a pivotal role in lifting Sheri up out of the darkest places that our minds can go when faced with life or death situations.

Charlie, Meghan, and I went to visit Sheri last night. She is still quite fragile and now her emotions are begining to bubble up at random points as it appears she is realizing how "this close" brushed up against her precious Antonio.

Antonio, I hope you are making your bull frog noise soon. Your mommy really, really needs to hear it soon. I hope those good vibes that Kim brought with her can somehow make their way through space and time and land on Amanda.

88

Today, my grandma Eve turned 88 years old. I've tried to imagine myself at the age of 88, and wonder if I'll be as eloquent, calm, stubborn, and diplomatic as she. What will unfold in my life between now and then, if I make it to 88 in the year 2060?

Will I still live in my own home?
Will I still drive my car, just around town?
Will I still cook? (Ha ha, my husband is laughing at that one.)
Will I revel in my children's accomplishments?
Will I revel in my grand children's accomplishments?
Will I revel in my great grand children, especially how they grow up so fast?
Will I still remember the subtle details of my life as she does?

Will I know how truly loved I am?
Will I know that my loved ones are dreading the "call" that will eventually come?

Tonight, Gram was her true self. She wouldn't let me ask much about her day. She wanted to know about me, my husband, my girls. Gram wouldn't have it any other way.

I got one hint from her though. She was extremely pleased that Mary Buchanan had sent her a birthday card. What made this such a blessing was that she believed her friend had passed on already. I could hear the happiness in her speech as it became rapid. She couldn't wait to tell me. Her pure joy emanated through the telephone as she expressed her friend from Oxford was alive.

Upon hearing the name, I had a flashback to being in a tiny church near Oxford and watching my grandparents greet the Buchanans before mass started. I was craning my neck to see their faces at about hip level on my Gram. Grandpa said, "Well, hi-a honey!" Mary smiled at me, and said, "I see the girls are up for a visit."

As conversations do, the topic eventually drifted to Grandma being proud of her three sons and how their families have blossomed. I suppose since birthdays make a person reflect, Gram revealed that she had actually had 5 pregnancies. "I was always so pleased that I had three boys, but I might have liked a daughter. I always thought that my miscarriages were my girls. You know my doctor wouldn't tell me whether they were boys or girls. She said it was better to focus on having another baby. I think she was right."

Well, Gram, you had to wait until 1972 to get me as your first grandchild. As you've told me multiple times, I know I've made you proud and that you love me. I love you too.

Happy birthday Grandma! I'm so lucky to have you in my life.

Love,
Jen

Pediatric Grand Rounds

Pediatric Grand Rounds is up at:

http://blogmd.samblackman.org/?p=307

Special thanks go to Blog MD for his compilation this round.

Promising Lung Research

Scientists develop new procedure to differentiate human embryonic stem cells

Molecular scientists at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) – which is part of the University of Texas Health Science Center at Houston – have developed a new procedure for the differentiation of human embryonic stem cells, with which they have created the first transplantable source of lung epithelial cells.

The process, created in the laboratory of Rick A. Wetsel, Ph.D., a professor of molecular medicine at the IMM, is described in this week’s edition of the Proceedings of the National Academy of Sciences. Research scientist Dachun Wang, M.D., is lead author of the article, “A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.”

“We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells,” said Wetsel, noting the procedure also can be used to create other types of highly-specialized cells.

Scientists at the IMM used the in vitro method to create lung epithelial cells known as alveolar epithelial type II. The cells were derived from a human embryonic stem cell line approved by the National Institutes of Health (NIH).

The method involves the use of protein markers under the control of cell-specific promoters to convert undifferentiated human embryonic stem cells into highly-specialized cells. The human embryonic stem cells were cultured on specially coated dishes and transfected with a lung epithelial gene regulator of a drug selection gene.

“It is a general technology for developing select cells from human embryonic stem cells,” said C. Thomas Caskey, M.D., the IMM’s chief operating officer, director and CEO-elect. “The technology has allowed us to develop a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others.”

James T. Willerson, M.D., president of the UT Health Science Center at Houston, said " I believe this is an important development by the Wetsel laboratory at the IMM. I look forward to seeing its transitional impact."

Alveolar epithelial type II cells are called “the stem cells of the lungs” because of their versatility and many important functions. They produce proteins including surfactant that inflates lungs. They also make other cells lining the inner lung. “They regulate lung fluids and oxygen levels,” Wetsel said.

The cells are part of the tiny air sacs lining the lower airways known as alveoli. Tissue thin, they transfer oxygen into the blood and remove carbon dioxide. If the walls of the hundreds of millions of alveolus in a pair of lungs could be spread out and placed side by side, they would cover the floor of a classroom.

According to Wetsel, transplantable alveolar epithelial type II cells can be explored as treatments for pulmonary genetic diseases, acquired lung disease, as well as lung trauma caused by car accidents, gunshot wounds and sports injuries.

“These are the cells that can potentially be used for regenerative lung repair,” he said.

Hereditary lung disorders most likely to benefit from transplantation of alveolar epithelial type II cells include respiratory distress syndrome of the newborn, alpha-1 related emphysema and cystic fibrosis, Wetsel believes. “All three of these diseases are caused by single gene defects and therefore have been logical candidates for gene therapy,” Wetsel said.

Respiratory distress syndrome of the newborn, a condition affecting premature infants less than 37 weeks of age, may be caused by a genetic mutation triggering a surfactant shortage. Likewise, alpha-1 related emphysema, a condition affecting 100,000 Americans, results from an inherited deficiency of alpha-1 antitrypsin. Further, cystic fibrosis is the second most common childhood onset inherited disorder in the United States.

Transplantable alveolar epithelial type II cells may also one day be helpful in the treatment of other lung diseases including chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States, claiming the lives of 122,283 Americans in 2003, and asthma, Wetsel said.

Still years away from their use in regenerative medicine, Wetsel said the next step involves research trials with mice.

Source: University of Texas Health Science Center at Houston


Source: http://www.physorg.com/news91879247.html

Powerful Denial

Sometimes, my overwhelming desire to believe that my children will be okay runs my life very effectively. I go through the normal day-to-day experiences of raising my girls without much thought for Alpha-1. Yes, I know that they have a life threatening gene. Yes, I know that right now, things are really great for them. Yes, I know I'm lucky to have my children with me to hug and hold. I guess what I'm trying to say is that most days, I have sort of a robotic response to thinking, feeling, or talking about Alpha-1. It is like I'm on autopilot.

I can rotely tell anyone about Alpha-1...what it is, why it affects my children, what we can and cannot do about it. I even devote volunteer time to Alpha-1 by serving on the board of directors of the Alpha-1 Association, Alpha-1 Kids, and the Alpha Pack, Wisconsin's support group. Monthly, I write a newsletter for Wisconsin Alphas, and daily, I monitor an online bulletin board for Alphas. I answer questions, provide support, and remind people in the Alpha-1 community that they are not alone.

Yet, here I am alone inside my own head tonight dealing with today's breakdown of powerful denial that protects this mother's heart.

In my last blog entry I described having interviewed an Alpha-1 researcher, Dr. Ronald Sokol. He is going to head up a groundbreaking research study of children with Alpha-1. All week, I've been thinking about how excited I am about this study, but here and there, a subtle realization kept creeping in my head. This study really is about my daughters and their genetic disorder. My babies have Alpha-1, and today, that is overwhelming the hell out of me.

This mom is about to order up a good dose of autopilot again.

Alpha-1 & the Cholestatic Liver Disease Consortium (CLiC)

Today, I interviewed Dr. Sokol from Children's in Denver. He is the principal investigator of the Cholestatic Liver Disease Consortium (CLiC), and in our conversation, he mentioned that a longitudinal study of Alpha-1 children is in the process of being approved. When it is approved, he will be able to share more details about the study. Can I just say YAY? :)

In any case, Dr. Sokol made it clear that he encourages the parents of children with Alpha-1 to sign up via the Contact Registry on the CLiC web site:

http://rarediseasesnetwork.org/clic

Oh and Dr. Sokol said both children pre- and post-transplant are encouraged to be participants. He said a goal is to answer that never-ending question of why some children with Alpha-1 have severe liver disease and why the majority of the others don't. Wouldn't it be great if they could answer that question?

One last thing, this study is international because there is a research center located in London. So, UK families, you are invited too.

WOW, I'm pretty psyched about the interview, can ya tell? You should have seen me before it though. I was a bundle of nerves. I'm not really sure why except that this means so incredibly much to me. Alpha-1 needs a cure now. My childrens' lives depend it as well as all of our Alpha friends. Long live the Alphas!

I signed Grace & Meghan up for the registry last year. Thank God for researchers like Dr. Sokol. I only hope more researchers are inspired by his great example.

Jen, the incredibly impressed parent of 2 Alphas

What a big girl!

Yesterday was Meghan's first entire day of wearing regular underwear. So, she is officially potty trained now. WOOHOO

Where has the time gone? To me, it seems like yesterday since she looked like this:














She is really quite proud of herself, and well, we are proud of her too. She has come a long, long way since being born 1 pound, 9.5 ounces. Way to grow up Meghan.

Ginormous

I thought I'd share a little of the childhood logic that appears at random times in our household. Before I tell you, know that Grace and Meghan are at ages where they have noticed differences between people. They know that ladies have boobies, but men still have nipples too. Here is a little of our conversation today:

Meghan pulls her shirt away from her neck and peers down into her shirt, and says "I have boobies."
Grace: "Me too. I have boobies. Mommy has big boobies."
Me: "Thanks Gracie, but I don't have big boobies."
Meghan: "I have big boobies!"
Grace: "No, you don't! God has ginormous boobies!"
Me: "What? Oh! (Laughter as I realize that Grace thinks God is a huge entity.) "Gracie, is God a man or a lady?"
Grace: "A man!"
Meghan: "I have boobies!"
Me: "Yes, you both have boobies."

Poster Child for Preeclampsia

Cross posting an entry that I wrote on the Preeclampisa Survivors blog:

http://preeclampsiasurvivors.blogspot.com/2007/02/ever-feel-like-poster-child-for.html

Neurodevelopmental Issues in Preemies

Hmmm...should I be glad about this post? Should I be sad?

Well, I'm just confused as of yet. I think I'll reread this one several times before I can completely digest it. In any case, having had 2 premature daughters, I want to know what I'm facing as they get older.

http://talesfromthewomb.blogspot.com/2007/02/neurodevelopmental-devastation-how-can.html

Great, just great...

High Blood Pressure in Pregnancy Boosts Lifetime Heart Risk
It's linked to hardening of the arteries in later life, study finds

By Ed Edelson
HealthDay Reporter

MONDAY, Feb. 5 (HealthDay News) -- High blood pressure during pregnancy is a warning sign of diabetes and heart disease later in life, a Dutch study indicates.

The study of 491 older, postmenopausal women found that those who had reported high blood pressure during a pregnancy had a 57 percent higher risk of developing calcium buildup in their arteries, compared with those whose blood pressure did not rise abnormally during pregnancy.

The findings were published online in the Feb. 5 issue of the journal Hypertension.

Calcification of the arteries is a marker of atherosclerosis or "hardening of the arteries," which is associated with an increased risk of cardiovascular disease.

"Our research and that of others may have important implications for the management of women who have high blood pressure in pregnancy," senior researcher Dr. Michiel L. Bots, associate professor of epidemiology at the Julius Center for Health Sciences and Primary Care in Utrecht, said in a statement.

The findings probably do not have implications for obstetric care, added Dr. Sharonne Hayes, director of the women's heart clinic at the Mayo Clinic in Rochester, Minn.

"We would still need to treat those women the same way as we now do during pregnancy," she said. "But now, those women have been marked as having an increased risk of heart disease. They have another marker of risk and need to be much more vigilant in looking for cardiovascular disease."

Previous studies have led to "a growing recognition that complications, and particularly cardiovascular complications, during pregnancy lead to an increased risk of heart disease later on," said Hayes, who is chair of the scientific advisory board of Women Heart: A National Coalition for Women With Heart Disease.

"As far as I know, this is the first to look at coronary calcification, which is a very good marker for the presence of cardiovascular disease," she said.

The U.S. National Heart, Lung and Blood Institute estimates that 6 percent to 8 percent of American women develop unusually high blood pressure during pregnancy. Some go on to develop a condition called preeclampsia, which can damage the placenta, kidney, liver and brain. A more serious condition, called eclampsia, is a leading cause of pregnancy-related mortality.

The increase in calcification in the Dutch study was seen not only in women who developed preeclampsia but also those with high blood pressure, Hayes noted.

"It is a sign that you need to be more careful about your risk of heart disease down the road," she said.

The women themselves and their physicians should be aware of their increased risk, said Dr. Daniel Jones, dean of the University of Mississippi School of Medicine and president-elect of the American Heart Association.

"In women who have had hypertension during pregnancy, there needs to be careful monitoring of cardiovascular risk factors, to [help them] be prepared appropriately to manage those factors," Jones said. "These women should be doing what we all should be doing -- keeping their weight in a good range, exercising, not smoking, eating a diet high in fresh fruits and vegetables."

The study, he said, "is a new way of looking at an issue that we have long suspected is a problem: that women who have hypertension in pregnancy are more likely to develop hypertension later in life, and hypertension is a known risk of vascular disease."

SOURCES: Sharonne Hayes, M.D., director, Mayo Clinic Women's Heart Clinic, Rochester, Minn; Daniel Jones, M.D, dean, University of Mississippi School of Medicine, Jackson, and president-elect, American Heart Association; Feb. 6, 2007, Hypertension

Copyright © 2007 ScoutNews, LLC. All rights reserved.

Latest Developments

Quick update on me:

Last week, I came down with a nasty upper respiratory virus. This weekend, I felt like my nose was a faucet.

Now, it has settled into my left lung again. This is getting so old.

I think I’ll be making an appointment with my doctor again. I’m short of breath again, and frustrated with what feels like a repeat of my lung infection in December.

In other news:
I’m still investigating sensory processing disorder in how it relates to Gracie. I’ll post more soon, but wow, this seems to be the light at the end of the tunnel finally.

Darn preeclampsia! Darn premature birth! Darn my body and what it did to both of my Alpha Girls!

Terse Jen

Donated to Locks of Love

On Saturday, I got my hair cut. And when I say hair cut, I mean huge amount of hair cut off. ha ha Here is the BEFORE shot, taken with Gracie's digital camera:
















I had 12 inches cut off to make 5 pony tails worth of hair to be donated to Locks of Love (http://www.locksoflove.org). I guess you could say that I have a bit of hair shock, but I'm so happy I did it.

When Meghan was born and needed 3 transfusions, I wasn't able to donate blood to her because I had just given birth. I decided then that I would grow my hair out and donate it because it seemed to be all that I could do in those scary NICU days.













Well, the day finally arrived and a little over 2 1/2 years later, my hair is now gone. I need to mail it off to be made into a wig.

Discharged from NICU Follow-Up Clinic

Today, Meghan had her 30 month adjusted check up at our NICU's follow-up clinic. I was so happy because Meghan's chief neonatologist, Dr. Ragatz, was on the follow-up clinic rotation today. It was nice to see him again, and he said it is so rewarding to see his former micros succeed.

We received the best news today. They feel that Meghan has come so far that they no longer are talking to us about cerebral palsy (CP) anymore. Her asymmetry (left-sided weakness) is virtually gone with just a tad in her left arm, which they feel should continue to fade to none with some more time and physical therapy.

WOOHOO!!!! This is such a relief. I can't tell you how many times I mulled over and cried about her possible CP over the last year. This is seriously the best news for Meghan. I'm so happy that I feel like I'm floating on air. Can ya tell I'm happy? :)

Today, Megs received an OT consultation using the Bailey scale. Her assessment came out to be a 34 month old. Another WOOHOO moment.

Finally, they gave us her height and weight. DRUM ROLL please!!!!!!!!!

25 pounds 1 ounce
33 inches

She is in the 29 1/2 percentile for height, and in the 25th percentile for weight. WOOHOO

I can barely believe this. Way to grow Meghan! Gotta love cyproheptadine.

They discharged Meghan from follow-up clinic, and asked us to submit our story to our hospital's Little Angels foundation for both Meghan and Grace. We've been visiting the Follow-Up clinic since Grace was born so they've gotten to know us pretty well.

Thanks for "listening" to my glowing report. I promise I'll be more humble next time.

Proud Mama Jen

Jen's Lense

For those of you who wonder about my experience with preeclampsia, please read this post from one of my Internet pals and heros:

http://preeclampsiasurvivors.blogspot.com/2007/01/my-lens.html

This account is so eloquently stated and elaborated on how most women who've had preeclampsia feel.

Gene Chip Discovery

This is so cool! I wonder if Alpha-1 is one of the hereditary diseases for which the gene chip tests. WOOHOO for Cincinnati Children's. UPDATE: the chip does test for Alpha-1. This is so awesome! :)

December 22, 2006 - Gene Chip Discovery May Lead to Individualized Treatment for Five Hereditary Liver Diseases
Research Published in the Journal, Gastroenterology

Researchers at Cincinnati Children's Hospital Medical Center have developed the first gene chip to use in the early diagnosis of at least five hereditary liver diseases, to detect genetic causes of jaundice in children and adults, and potentially to lead to personalized treatment options.

The chip, termed the "jaundice chip," is nearly 100 percent effective in the detection of the most common mutations in children with inherited causes of jaundice, according to a new Cincinnati Children's study in the January issue of the journal Gastroenterology.

"Other chips have been developed to assess drug metabolism," said Jorge Bezerra, MD, a pediatric gastroenterologist at Cincinnati Children's and the study's lead investigator. "This is the first chip in the world that has been customized to diagnose genetic mutations in patients with inherited types of liver diseases."

The chip uses a new technology that rapidly and accurately discloses the composition of several genes known to cause liver disease in children and adults. "The jaundice chip may also help us to discover whether subtle changes in these five genes that can cause devastating diseases in children may also modify the clinical course of other common liver diseases in adults," said Mitchell Cohen, MD, director of the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's.

Jaundice is a yellowing of the eyes and skin caused by impairment in bile flow from the liver to the intestine. Impaired bile flow, or cholestasis, commonly known as jaundice, can lead to severe liver disease. In children, jaundice and cirrhosis are responsible for more than half of the need for liver transplantation.

Previous research on humans identified five genes responsible for inherited forms of jaundice. Until now, the broad array of causes of cholestasis including genetic, metabolic, inflammatory and drug- or toxin-induced disorders, created a challenge for physicians to diagnose a specific disease. Therefore, the treatment of affected children was not disease-specific and aimed at optimizing care to help reduce liver transplantation. With the jaundice chip, however, diagnosis can be simplified by surveying the genetic code for mutations in specific diseases.

The jaundice chip was designed as a "five-in-one" gene chip to screen mutations (a permanent change in the DNA sequence that makes up a gene) in five genes using only one milliliter, or less than a half of a teaspoon, of blood. Gene chips contain several thousand small fragments of DNA on a small piece of glass. Incubation of these chips with the patient's DNA sample produce chemical signals that "glow" and allow for the detection of the normal gene sequence, or of mutations if they are present in the patient.

"The jaundice chip is an extraordinary advance for our patients with liver diseases. It will improve diagnostic accuracy for perplexing diseases in infants and children, potentially decrease the need for invasive and costly studies, and allow us to develop specific treatment plans based on the correct genetic diagnosis," said Dr. Cohen.

"With further genetic testing of liver disease, there is the potential that medications can be tailored to meet the needs of individual patients taking into account the patient's genetic make-up," adds Dr. Bezerra. "For now, the use of the gene chip gives families piece of mind, knowing what their child is living with. The next focus of advances will be the development of medication that may block progression of their disease.

Today, detection of liver diseases with the jaundice chip is continuing, using samples from children worldwide through a research protocol in the division of gastroenterology, hepatology and nutrition at Cincinnati Children's. Once approved by the Food and Drug Administration, the potential for wider use is limitless, according to Dr. Bezerra.

The discovery of the jaundice chip was made possible through a grant from the Research Foundation at Cincinnati Children's with additional support by the National Institutes of Health (NIH).

Cincinnati Children's Hospital Medical Center, one of the leading pediatric research institutions in the nation, is dedicated to changing the outcome for children throughout the world. Cincinnati Children's ranks second among all pediatric institutions in the United States in grants from the National Institutes of Health. It has an established tradition of research excellence, with discoveries including the Sabin oral polio vaccine, the surfactant preparation that saves the lives of thousands of premature infants each year, and a rotavirus vaccine that saves the lives of hundreds of thousands of infants around the world each year. Current research directions include the translation of basic laboratory research into the development of novel therapeutics for the treatment of disease, and furthering the development of personalized and predictive medicine.

Angiotensinogen and Alpha-1 Antitrypsin Genes

I found this study abstract on PubMed. It is intensely interesting to me because I have a form of hypertension that falls into the angiotensinogen category, and I also carry the MZ Alpha-1 gene. People who have the angiotensinogen gene have increased risk for developing preeclampsia. I wonder how all of this works together. I suppose I'll never know since I'm not a doctor, but I'll always had reason to suspect I developed PE in relation to my Alpha-1 status. Scientists are always talking about modifier genes...thoughts that make me go...hmmmmm.

J Biol Chem. 1984 Jul 10;259(13):8063-5. Related Articles, Links
Common structural organization of the angiotensinogen and the alpha 1-antitrypsin genes.

Tanaka T, Ohkubo H, Nakanishi S.

A rat genomic DNA segment containing the angiotensinogen gene has been isolated from a gene library by hybridization with a restriction fragment derived from a previously cloned cDNA for rat angiotensinogen. Restriction mapping and nucleotide sequence analysis of the cloned DNA fragments have indicated that the rat angiotensinogen gene is approximately 11.8 kilobase pairs long and consists of five exons separated by four introns. Because it has recently been reported that the sequence of angiotensinogen significantly resembles those of alpha 1-antitrypsin and ovalbumin and also that the exon-intron arrangements of the alpha 1-antitrypsin and ovalbumin genes are completely different, this study compares the structural organization of the angiotensinogen gene with those of the alpha 1-antitrypsin gene and the ovalbumin gene. The comparison has revealed that the four introns of the angiotensinogen gene are all located at the positions equivalent to or corresponding to those observed in the alpha 1-antitrypsin gene, suggesting that the angiotensinogen gene and the alpha 1-antitrypsin gene have diverged from a common ancestor gene. This finding raises interesting possibilities regarding the biological function of angiotensinogen and the evolution of the angiotensinogen gene.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 6330095 [PubMed - indexed for MEDLINE]

Gracie Picture

IMG_1592
Originally uploaded by jenchar.

Meggie Picture

IMG_1593
Originally uploaded by jenchar.

Confessions of a Former Little Girl

Let me start off this posting by saying that I'm blessed to have 2 beautiful children. I love them very much, and try to cherish them every day.

With that said, I also want to say that it has been quite rough in the land of B family parenting lately. I swear if I hear one more little girl scream come out of the mouths of my girls, I think I might scream my way all the way to the funny farm.

"No, its mine."
"Nut uh!"
"Yes, Dace!"
"No, Meghan!"
(Insert high pitched, ear drum piercing 2 year old scream here followed by even more annoying high pitched, brain draining 4 year old scream here.)

That is just a sampling of a conversation that seems like it has been put into reruns in our every day lives.

I keep wondering just what exactly we've done wrong as parents to have such ungrateful, unloving children. I'm sure these are not unique parental feelings, but can I just say "Ugh!"

And to my mom and dad, I'll just add one last thought:

I'm sorry for any past pain and suffering I caused you by screaming one of those little girls screams in my childhood. I swear I did not know what it did to you, but I probably did know what it did to my loving lil sister, Kristen.

(Insert sound of my parents laughing their asses off here.)

What's that phrase? Ah...ain't payback a B@#$%?

I'm LOL or else I'll scream my head off at the girls.

Anyone know anything about sensory integration disorder? Inquiring minds want to know...

Meghanisms

Viniman instead of minivan

Dace instead of Grace

Mary had a lipple lamb

I'm a kitty!
Really Meghan, you're a kitty.
Uh huh.
What color kitty are you?
I'm a pink kitty.
What color am I?
Black.
What color is Daddy.
Black.
What color is Gracie?
Black.
What color are you?
Pink.

Norovirus

On December 23rd, I was wrapping gifts in our rec room, and heard "Jen, Meghan just puked." I walked up the basement stairs to hear whimpering from Meghan, the puker. She was covered in it and so was my mom (the pukee) who had tried to help her. Upon entering the living room, I smelled THAT smell. You know. That horrible, awful virus puke smell. I'm sure any day care provider could identify it as the "smell smelled round the world." haha

In any case, this began Megs nonstop episode of consistent vomitting for nearly 8 hours into the wee hours of Christmas Eve. I spent much time cleaning up Meghan in baths, scrubbing soaked clothes, cleaning the carpet, and washing my hands over and over again. I was hoping beyond hope that I wouldn't catch the ick, but in the back of my mind, I kept remembering that I was still on prednisone for my bronchitis. Right on the package, it said something to the effect of this medicine can lower your resistance to infection.

Upon the puking ending, Meghan then started with the worst smelling BMs. She put pig farm smells to shame. Even the flys wouldn't come around her. Poor baby...In any case, our Christmas experience in the B family household was a bit lacking. We were too busy being covered in puke to get into the spirit of the holiday, but we still went through the motions.

Ultimately, we made it to Christmas morning. Charlie and I were a bit blurry eyed due to the normal parent experiences during the wee hours of Christmas morning. About 1/2 hour before the girls woke up, I came down with a nasty migraine headache. Merry frickin Christmas! Sorry if that offends you but this holiday is going down in the number one spot on my list of worsts. Ooh la la! How wonderful! A blinding, raging headache to go with your Christmas cheer.

After the headache had been dulled a bit, we opened our gifts. The girls were quite pleased with what Santa brought, but Meghan's pallor was ghastly to say it nicely. Plus, she gifted us with some of those lovely scents of ransid, rotting flesh in her diaper.

In any case, Meghan seemed to be past the worst of norovirus, and I was glad that she was a bit better. Well much to my chagrin, Meghan was sitting nicely in my lap helping me to open one of my gifts and suddenly hurled into the very convenient gift bag I was "opening." Thus, commenced round 2 of puke fest 2006. Eeeeeeewwwwwwww!

So, is anyone wondering if I acquired this ick yet?

DA DA DA DA DAAA DAAA DAAAA (say that to the theme of STAR WARS)

I awoke on 12/26 to a fun filled festival of pukiness too. 12/27 was a day of visits to the potty for me too.

So there...there was my holidays wrapped up in a nutshell.

Wasn't this the most pleasant posting I've ever written?

Yours in norovirus recovery,

Jen

PS: Somehow, Charlie and Grace have evaded the fun. I hope that doesn't change. I've already "boiled" myself and everything around me to minimize germs. :)

Boston Marathon

Today, I found out that a runner in the Boston Marathon will be running in honor of Grace & Meghan. Her name is Jen, too.

In any case, I'm so excited about this. It just means so much to me that someone else is thinking of my girls. We are so blessed for their current state of good health, and I'm honored that the girls were matched up with Jen.

She is part of a team made up of about 230 runners, who last year raised over $1.1 million for the American Liver Foundation. The team goal this year is $1.2 million. Over the past 3 years, Jen has personally have raised over $20,000. Her goal this year is $8,500.

Isn't that awesome!

The marathon is on Grace's 5th birthday, and we'll be routing for Jen all the way...from Wisconsin. :)

Ho, ho, ho…I’m sick

Last week, I caught one of the nastiest colds I’ve had in a very long time. My nose was rather faucet-like. ha ha I think I caught the bug that Meghan had to fend off with antiobiotics recently.

Today, I took myself to the doctor because my left lung hurt. I’ve never had lungs hurt before. I also have a very nasty “chunky” cough with lots of Christmas green color “things” to use a technical term. I guess you could say that my Alpha-1 radar was up.

Being that I’m a gene carrier (MZ) for Alpha-1, I know that I have less Alpha-1 circulating in my blood stream to fend off this particular nasty infection. I do admit that I say that with a little hesitation, since I don’t want to state my case as being horrible when compared to the many individuals who live with ZZ Alpha-1 on a daily basis. ZZ Alphas certainly deal with much greater consequences of repeat lung infections. In any case, I thought it wise to protect my lungs by telling the doc about my recent illness.

Well, my dear old doc informed me that I’m wheezing pretty badly especially on my left side. So, guess what? I get to take prednisone, a steroid to reduce the inflammation in my lungs, along with an antibiotic for 10 days.

Fun, fun, fun

Cough, cough, cough

Ho, ho, ho

I hope to be better by Christmas.

NICU Reunion

Cross posting an entry I wrote on Preeclampsia Survivors:

http://preeclampsiasurvivors.blogspot.com/2006/12/nicu-reunion.html

Jen

Always See the Bright Side

Today while I was dropping Meghan off at her day care, Grace looked at the back of our filthy mini-van and said, "Mommy, why is there a rainbow on our car?"

I paused for a moment and thought, "Huh? Rainbow?"

As I examined the back of our van, I noticed the perfect shape of a rainbow on our back window. It was the only clean spot on the back of the van...exactly where I had turned on the window wiper.

This made me laugh since I was being the jaded, scruntinizing adult that I am. Gracie simply saw something pretty in the middle of something so dirty. All I saw was the filthy, gray "guck" on the back of my van.

I need to act more like a 4-year old from now on.

Jenni Richters

My sister reminded me of how my baby brother, Timmy, used to call one of my high school friends Jenny Richters. Her name was then Jenni Richter. It made me laugh since I accessed a very archived memory. I had almost forgotten that.

Jen, are you out there? Tim is now almost 22. Come out, come out whereever you are.

"What? Drop your face?"

"Look at all the snow men!"

Missing you my friend...

Jen :)

Bronchitis

Well, I took Meghan into the doctor today. She has had a cough that got gradually worse, and thus worried Alpha mom Jen. Meghan's cough reminded me of someone who had been a smoker for years. Ick! She is now on Zithromax and hopefully, it should do the trick.

So what I just described probably sounds like normal "mommy" stuff, right? You are right except...

Every time Meghan gets a lung infection, it means she loses healthy lung tissue, too. Since she is a ZZ Alpha, her body is not able to produce enough Alpha-1 in her liver to be sent to the lungs to turn off neutrophil elastase. Those neutrophils are like minature pac-men who come in and eat up the bad stuff hanging out in Meghan's lungs. Unfortunately, Meggie doesn't have enough Ms. Pac-Man (aka Alpha-1 proteins) to nag, nag, nag, nag the heck out of Mr. Pac-Man (aka neutrophils) until he finally backs down and stops destroying healthy lung tissue.

Fortunately, my mommy instincts kicked in about Meg's cough today, and we caught her bronchitis in an early stage. I'm grateful for that, but I can't quite turn off that obsessive thought of how much lung tissue will be destroyed with this infection. These are my inner most thoughts, and well, are now shared with you all in cyberspace. Getting my thoughts out into a narrative is what helps me to feel better.

In any case, Megs was so cute at the doctor. She actually cooperated since I was able to tell her what the doctor would do before he came into the room. When he walked into the room, she told him, "Just listen, right?" Funny...

"I has medcines. Make me fee betta. I go docta's room."

She is growing up so fast now. I can't believe how much she is talking and figuring things out now.

Juxtaposition

Today, I was late getting the girls up to get ready for school and was still at home about 20 minutes after I should have been. While ironing a very wrinkled set of pants for myself around five after eight, I heard a very loud "metalic" crashing sound almost as if something had fallen over.

I thought, "What the heck was that?"

I peaked out my window to look into our alley, but didn't see anything. I figured it must have been someone getting one of those huge metal dumpsters delivered, but then I thought, hey everyone has snow on their roofs so it can't be a roofing dumpster...strange. In any case, I quickly put the strange loud noise out of my mind.

Then, I proceeded to go about scurrying the kids off to school. When I arrived at work, my hubby had left me a message telling me to get online to see the huge explosion that had happened about 8 miles from my house.

The Falk Corporation complex here in Milwaukee which does metal forging, etc...literally blew up today. Two full city blocks are gone in the valley near Lake Michigan...when I saw the coverage on CNN.com, it looked like 9/11 again...they think it was just an accident with a gigantic propane tank. Thankfully, it sounds like an evacuation was in progress because of the smell of gas. It could have been much worse, but horribly, three people died and another 50 or so people were injured some critically.

It was upsetting to me that as I was chastizing my kids for being pokey, people were dying or literally running for their lives. I so very much feel for the families of those men who died...they all had young children and wives. Certainly, this makes me feel grateful for all of the blessings in my life, and I'll be praying for all of the victims of this tragedy.

It was very strange juxaposition at least in how I experienced it.

Please pray for the affected employees and families.

All I Want for Christmas...

As I've gotten older, I've noticed that I'm less inclined to "want" for physical items. Our family is already so blessed with a home, cars, food to eat, clothes to wear, toys to play with, and other extravagences. So, this year for Christmas, I'd rather have my family and friends donate to some very worthy causes, which are near and dear to our hearts, rather than receive gifts.

The Alpha-1 Foundation is dedicated to providing the leadership and resources that will result in increased research, improved health, worldwide detection, and a cure for Alpha-1 Antitrypsin Deficiency. Since both Grace & Meghan have ZZ Alpha-1, we'd love it if you could help fund research for Alpha-1. 100% of what you donate goes to research. The Alpha-1 Foundation has other ways of generating the money to run the business side of the foundation.

Donate at: http://www.alphaone.org/help/commemorative-giving

The Make a Wish Foundation grants the wishes of children with life-threatening medical conditions to enrich the human experience with hope, strength and joy. Several of our liver friends have been granted wishes and their experiences were invaluable. Please share in helping critically ill children find some joy in their lives.

Donate at: http://www.wish.org/help/donate

The Curative Foundation, which runs our Birth to Three Program provides pediatric outpatient therapy services and special education to children ages birth to 3 years in Milwaukee County who have a developmental delay. Our little peanut girl, Meggie, has received speech, occupational, and physical therapy from this organization for the last 2 years. She is thriving because they've shown us how to help Meghan on a day-to-day basis so that she can overcome her former micropreemie beginning.

Donate at: https://www.curative.org/form/gift_form.htm

The March of Dimes' mission is to improve the health of babies by preventing birth defects, premature birth, and infant mortality. Both of our daughters were born premature due to my preeclampsia. Both of them suffer the side effects of being born preemie. Yes, they are doing well, but they both wear the "badge" of prematurity still. Please give generously.

Donate at: https://www.marchofdimes.com/howtohelp/donation_in_honor.asp

Have a very magical holiday season! Thank you for considering these organizations.

Jen

I'm Sad...

Today, I dropped Grace off at her before school day care program. When I was walking down the hallway out of the school, Shanna stopped me. She said she wanted to tell me something that Grace said to her the day before when they were having some bonding time.

Me: "What did Grace say?"
Shanna": "I'm sad I was born with Alpha-1."
(Hmmmm...but I remained calm. Guess mom Jen was having a good day emotionally.)
Me: "What were you talking about?
Shanna: "I think it was about painting finger nails."

Tonight before I put Grace to bed, I asked her about why she was sad she had Alpha-1.

Grace: "Because I can't paint my finger nails."
Me: "Grace, you can have painted finger nails sometimes. We just have to be careful because of fumes. We can paint your nails in the back yard where the wind can take the fumes away."
Grace: "What are fumes?"
Me: "They are like stinky smells that hurt our lungs."
Grace: "Oh."
Me: "What color nail polish do you want Gracie?"
Grace: "Blue with glitter like Aisha from school."
Me: "How about pink? Or purple?"
Grace: "I like red and green."
Me: "Just because you have Alpha-1 doesn't mean that you can't have painted nails Gracie. We just can't do it too much. It is more important not to smoke cigarettes or drink alcohol."
Grace: "Ok. What is alcohol?"
(Oh boy...)
Me: "A drink that makes people act silly but it hurts their livers. We don't drink alcohol because we are Alphas, right?"
Grace: "Right."
Me: "We'll paint our nails some pretty colors. It will be fun."

Grace gave me a hug. Her Alpha-1 realizations are coming fast and strong now, but I'm proud she talks about it with people she loves. Way to grow Gracie!

Angiotensinogen Thr235 Mutation

Have always been interested in why the heck I got preeclampsia, but when I developed chronic hypertension after the birth of Meghan, things started to make sense. Hypertension runs in my family, and the medication that I take is an ACE inhibitor, which is an antiangiotensingen controlling enzyme (ACE). This study abtract makes me wonder...I never had a placental abruption though. I suppose my mom and Aunt Susan might like to read this. Let me know if you do Mom or Susan.

1: Placenta. 2006 Nov 17; [Epub ahead of print]

Placental Abruption Is More Frequent in Women with the Angiotensinogen Thr235 Mutation.

Zhang XQ, Craven C, Nelson L, Varner MW, Ward KJ.
Department of Obstetrics and Gynecology and Reproductive Genetics, University of Utah, School of Medicine, 50 N Medical Drive, Wintrobe Building Room 657, Salt Lake City, UT 84132, USA.

OBJECTIVE: Obstetrical complications such as preeclampsia, fetal growth restriction, and placental abruption are associated with inadequate placental perfusion. Previous studies have shown that the angiotensinogen (AGT) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in preeclampsia. This study was done to evaluate whether the AGT Thr235 mutation increases the risk of placental abruption. MATERIALS AND METHODS: We compared 62 placentas from women who had placental abruption with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. AGT Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system. RESULT: AGT genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of AGT genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). AGT mutant allele frequency in placental abruption (0.637) was significantly higher than in the control group (0.377) (p<0.001). CONCLUSION: The AGT Thr235 mutation was observed more frequently in placental abruption. AGT Thr235 mutation may be considered a risk factor for placental abruption.

PMID: 17116328 [PubMed - as supplied by publisher]

Promising Alpha-1 Gene Therapy

I heard about this research last February at the Alpha-1 Foundation's Research Update. While this is very promising because it did no harm to study subjects, there is much to be done before this can actually be used as an effective therapy. I still applaud this research, and encourage you to support the Alpha-1 Foundation (http://www.alphaone.org) in its quest to fund a cure for Alpha-1. WOOHOO! :) Jen

Gene therapy shows promise against hereditary lung disease

Tuesday, November 21, 2006. GAINESVILLE, Fla. — An experimental gene therapy to combat alpha-1 antitrypsin deficiency, a common hereditary disorder that causes lung and liver disease, has caused no harmful effects in patients and shows signs of being effective, University of Florida researchers say.

In a clinical trial, researchers evaluated the safety of using a so-called gene vector — in this case an adeno-associated virus — to deliver a corrective gene to 12 patients who are unable to produce a protein essential for health called alpha-1 antitrypsin.

“The primary end point in the trial was to see whether it was safe to give patients this gene transfer vector and then to try to begin to see if we could get the dose into a range where we would begin to replace the missing protein in the blood,” said Dr. Terence Flotte, a pediatrician, geneticist and microbiologist with UF’s College of Medicine and a member of the Powell Gene Therapy Center and the UF Genetics Institute. “We found that we can use this agent safely and we also saw evidence in the patients’ blood that the higher doses successfully introduced the vector DNA. In one patient we saw evidence for a very brief period that some of the alpha-1 protein was being produced, but not at a high enough level to be beneficial.”

The findings appeared online today (Nov. 21) in the journal Human Gene Therapy.

Physicians injected doses of the virus containing copies of the gene for alpha-1 antitrypsin into the patients’ upper arms. Essentially, the virus is intended to “infect” patients’ cells with replacement genes that will do the necessary work to produce alpha-1 protein. UF scientists have successfully developed the technique in animal models.

The next step is to test the therapy with a different version of the adeno-associated virus; about 200 variations of the virus exist in nature.

“We have another version of the virus that appears in animal studies to be close to a thousandfold more potent at making protein,” Flotte said. “That’s very encouraging to us. So the next trial, which has already begun, is to use the new version of the virus and take patients through a similar range of doses, in a very similar scheme, and see if we can maintain the safety while pumping up the efficiency of the protein production.”

In most people, alpha-1 antitrypsin is made in the liver and protects the lungs by counteracting inflammatory products that destroy lung tissue. But about 100,000 Americans have alpha-1 antitrypsin deficiency, according to the Miami-based Alpha-1 Foundation, a national not-for-profit organization devoted to finding a cure. In addition, medical authorities suspect less than 5 percent of affected individuals are diagnosed, often not until they are in their mid- to late-30s, after extensive lung damage occurs. Shortness of breath, wheezing, chronic cough and recurring chest colds are signs of the disease.

It is important that alpha-1 patients avoid cigarette smoke, said Dr. Mark Brantly, a professor of medicine and molecular genetics and microbiology at UF’s College of Medicine who develops clinical research programs aimed at developing therapies for alpha-1 patients. Alpha-1 deficiency can in some patients lead to emphysema and cirrhosis, both progressive diseases that can be fatal.

Alpha-1 patients with symptoms of emphysema can be treated through weekly intravenous injections of alpha-1 protein derived from human plasma. The injections must continue throughout a patient’s life, according to the American Lung Association. It does not cure, but it does appear to slow the progression of this disease.

Patients in the clinical trial – 10 men and two women who ranged from 42 to 69 — were asked to discontinue their replacement therapy 28 days before receiving the gene therapy.

One volunteer who had not been on protein replacement therapy exhibited low-level expression of alpha-1 antitrypsin, which was detectable 30 days after receiving an injection. However, residual levels of alpha-1 antitrypsin from the replacement therapy in the other patients obscured whether the alpha-1 gene had begun to express protein.

“As the authors conclude, the results set up the more interesting approach of using other AAV serotypes more suited for muscle delivery as an alternative with the same transgene in the next trial,” said Richard J. Samulski, a professor of pharmacology and director of the University of North Carolina’s Gene Therapy Center. “These studies are important milestones that allow the potential for gene correction of AAT to advance, as well as the (gene therapy) field in general. They also represent the step-by-step process established by the FDA and research community to ensure that safe and good clinical studies are employed in these early days, and I applaud Terry Flotte and his group for being cautious and thorough in their clinical design.”

The trial is funded by a National Institutes of Health grant, and the Alpha-1 Foundation played a crucial role in helping to build the infrastructure to support the research, Flotte said. UF holds an equity interest in Applied Genetic Technologies Corp., a company formed by UF researchers to develop gene therapies.

Miracles Aren't Free

Cross posting my entry on Preeclampsia Survivors:

http://preeclampsiasurvivors.blogspot.com/2006/11/miracles-arent-free.html

Long Live the Alphas

Yesterday, I attended another Alpha-1 education day in Chicago. I always look forward to attending the days. I think that is because I keep hoping that one of these events will reveal that latest advance, the "ah ha" moment for some doctor who might be there, or possibly that glimer of hope for my beautiful Alpha daughters.

As is usually the case, I was sorely disappointed.

I know that I'm really quite lucky to have Alpha girls who are doing well. They are growing and learning about all the subtle nuances in life. I get to love, cherish, and hold them every day, and I always try to remember that there are parents of children with Alpha-1 who can't do that. Their precious children earned angel wings.

So some people might say that I'm torturing myself by attending these events. Some people might say that I'm wasting my time. Sometimes I wonder the same thing, but what those nay sayers don't know is what keeps me coming back.

Everyone in that room understands how important it is to find a cure for Alpha-1. Everyone knows how it feels. Everyone has felt the guilt of Alpha-1...the guilt of placing a burden on loved ones...the guilt of passing on a life threatening gene...the guilt of being less than perfect.

What makes these education days perfect is that we are all less than perfect in the room. We are all part of the Alpha-1 community. We all know how it feels. We all know that a cure must be found. My babies lives depend on it.

Long live the Alphas! Nay sayers be damned!

November is Prematurity Awareness Month

A little more than 4 years ago, I learned that my baby would be born too soon at 34 weeks gestation. My precious cargo, Grace Ann, had to be born early because of my preeclampsia. She was my biggest baby weighing in at 3 pounds, 14.5 ounces, and 17 1/2 inches long. She had difficulty breathing, eating, and growing. To this day, Grace still deals with issues related to her prematurity, but nonetheless is doing well overall in kindergarten. Can she really be 4 already? Wow! I'm eternally grateful for Grace and the wonderful neonatal care she received.

A little more than 2 years ago, I learned that my second baby would be born extremely too early at 27 weeks gestation. My tiny peanut, Meghan Rose, was born because I developed preeclampisa yet again. She was unbelievably small to me weighing in at just 725 grams, aka 1 pound, 9.5 ounces, and 13 inches long. She was called a micropreemie, and proved herself to be a fighter every scary step of the way. Today, she still contends with issues related to her prematurity, too. We're happy she is growing, albeit ever so slowly, but she is happy and quite the character. :)

Every day 1 in 8 babies born in the U.S. arrives too soon. Premature birth can happen to any pregnant woman. It is a serious, common, and costly problem. The March of Dimes is leading the campaign to reduce premature birth by supporting research and by educating the public and health care providers.

In tribute to the miracle baby survivors of preeclampsia, please consider donating to the March of Dimes. I would be so proud if you could. Grace & Meghan thank you too.

Jen, mom of Grace & Meghan

Already?

When I came home from work today, Gracie bolted up our basement stairs from the play room and squeezed her arms around my waist. I hugged her back, and said, "Did you have a good day?" She stuck her bottom lip out and said sighing, "No." Meghan then interupted by saying with delight, "Mommy home!" Grace disappeared behind me.

As I took my coat off, I walked around calling for Grace. She answered me with "I'm in here in the living room."

"Where?"
"In here!"
"Where?"
"In the corner by the table!"
"Why?"
"I just like it here, Mom."
"Why? What are you doing?"
"Nothing. I just like it here."

(I'm now thinking...what is up with her? In fact, I thought that she might be pickin' her nose or something, but as is usually the case for me, I was distracted by many things...the mail to be opened, my hubby telling me various things, wondering about the election results, noticing that it looks like a bomb went off in my house, and remembering that Charie and I had German class tonight...dang it, I forgot!)

A little while later, I went up to the girls' room to pick out their clothes for the next day. Grace followed me upstairs. Then, I remembered I should check the school calendar to see if Grace needed to wear her gym shoes tomorrow so I went back downstairs for a quick minute. When I came back into the girls' room, I found quite a mess on the floor that hadn't been there just the minute before. There were books everywhere, a dolly stroller overturned, stuffed animals strewn about, and dirty clothes taken out of the hamper and scattered on the floor.

WTF?

"Grace, what happened?"
(no answer)

"Grace, what happened in here?"
(long pause)..."Meghan did it!"

"No, Meghan is downstairs with Daddy. What happpened in here?"
(no answer again)

"What is going on Grace?"
(Grace covers her face.)

"Are you angry?"
(no answer)

"Grace, if you don't answer, you'll get a timeout! Are you mad?"
(I suddenly see the ring of chocolate residue around her mouth and remember her hiding in the corner...my aha moment comes regarding the hiding, but I decide to talk to her about stealing from her candy stash without permission later.)

"You can tell me anything Grace. I won't yell."

"Yes, you will. You yell at me a lot." (Ut oh, busted!)

"No, I don't, but honey, what is wrong?"

"The girls were mean to me at school. I'm sad."

(I'm thinking...oh crap! I have no idea how to handle this yet. C'mon! Why do little girls have to be so dang mean to one another? What should I say to her? How can I let her know that it is okay to be sad about it, but not okay to throw things around because of it? Also, is this why she stole chocolate? Have I already shown her the errors of my ways in drowning my sorrows in chocolate? Crap! Where is Charlie when I need him? Ah, he's a man. He won't get this. He's never been a girl. Nothing against my hubby, cause I love him a lot, but he doesn't always understand girl "stuff.")

"They didn't want to play with me."
"Who didn't?"
"I don't know their names yet."
"Zoe?" (Zoe is Grace's best gal pal since they were about 4 months old.)
"Uh huh and some other girls."
"Gracie, remember how I told you that kids are still learning how to be good people and adults help children to learn how to be good people?"
"Uh huh."
"Maybe the girls still need to learn how to be nice? Or, maybe they were having a bad day? Sometimes, we have bad days, right?"
"Mom, Zoe said she wasn't having a bad day and told me to go away." (Crushing painful blow to my heart at this point. Why are girls so dang mean?)
"Gracie, you know that you are a good girl, and that sometimes, other people can hurt our feelings or make us sad, but that doesn't mean you aren't a good girl and nice to be around."
"Mom, they wouldn't play with me."
"I'm sorry that made you sad honey." (I gave her big hug.)
"Gracie, when Daddy picks you up from school and you've had a bad day, tell Daddy that you need a hug. Hugs can make you feel better, okay?"
(no answer)
"Now Grace, there are 3 things I need you to know. Number 1, you are a very special girl, and you should always be proud of yourself. Number 2, it is not okay to throw things when you are sad or mad. You can always talk to Mommy or Daddy...always. Number 3, if you feel like you want to eat something, it is not okay to take food without asking. Having chocolate before dinner is not okay with me. Chocolate is a sometimes food. Okay?"
(no answer)
"Let's pick up your mess and go downstairs to eat some dinner."

Gracie's face said it all. Her pain was real, and there was nothing I could do besides kiss her and give her hugs. I couldn't take her pain away though. She had hurt feelings, and damnit, I couldn't make her feel better. She sulked for most of the night about it even when my sister came over to watch the girls, and Gracie loves Lauren. Forgive my language please, but damnit, she is only 4!

Already??????

Damn it!

Cross posting one of my entries on Preeclampsia Survivors:

http://preeclampsiasurvivors.blogspot.com/2006/11/met-some-other-survivors-in-person.html

Jen

A Bright Idea

Today, I helped launch a new blog called Preeclampsia Survivors.

http://preeclampsiasurvivors.blogspot.com

I'm pretty proud of it since I helped conceive the concept and then worked it through to completion. I hope that other preeclampsia survivors will benefit from the blog.

It will grow in time, but I'm happy to help other PE moms feel less alone with their guilt over having had preeclampsia.

Maybe this time next year, we'll have regular bloggers contributing content. We'll see what lies ahead, but it was fun putting together.

Jen

Scientists Use Umbilical Cord Stem Cells to Grow Livers

Scientists Use Stem Cells to Grow Tiny Livers in Lab

British scientists used umbilical-cord stem cells to grow small artificial livers in the laboratory, a breakthrough that could be the first step in being able to grow full-sized livers for human transplants.

These tiny livers -- smaller than a penny -- can already be used for drug testing, reducing the need to conduct such tests on humans and animals, The Times of London reported.

The Newcastle University scientists placed the umbilical-cord stem cells in a bioreactor, a device developed by NASA to mimic the effects of weightlessness. In this gravity-free environment, the stem cells were able to multiple more quickly than normal. The scientists added hormones and chemicals to instruct the stem cells to turn into liver tissue.

"We cannot build a full-sized [liver] yet -- that will take about 10 years -- but this is the first important step," researcher Nico Forraz told The Times. "And we have excellent facilities... to be able to make this happen. We expect this to really take off within the next 18 months or so."

Source: www.healthday.com

A Beautiful Soul

An extremely tiny, beautiful soul entered Heaven on Friday.

Only his mother and father truly knew him. They knew his potential, his unending love, and what could have been his future. Even though I never met him, I feel as if I knew him inside and out. I'm not sure that makes logical sense, but I'll try explaining.

I simply knew of him as Jack.

He was growing inside my friend, Jack's mom. His mommy was so proud to be creating him that she told me when she was only 5 weeks pregnant. It was a secret, but I was absolutely honored to know my friend would become a mother. I was elated for her, and glad to have a new mommy to welcome to the world of parenting.

Even through all day sickness, Jack's mom was a fighter. Her strong and bright spirit helped her to keep her eye on the prize. Having also experienced all day sickness, I could sympathize immensely.

From the moment I first spoke with Jack's mom when I was 17, I saw her spirit was strong and bright. Even though Jack's mom didn't always know she was strong, I knew it. She proved it everyday that she would stay up late sharing her thoughts or just being silly with me. She never judged me or my circumstances. We had the best of times together. These times meant and still mean the world to me.

Unfortunately for Jack's parents, horrible circumstances unfolded. Jack's strong and bright spirit was held in a less than perfect body. He had to leave this world too soon, and leave his parents behind.

I've been praying for Jack and his parents. Even though they don't have him to hug and hold anymore, they will never forget their first born son, who made them parents. Jack's mom will forever be a proud mommy. Welcome to the club, Ames. I only wish you could have had more time with your dear sweet, little boy. I love you!

Oh and one more thing, hey Jack, up there with the angels, you need to know one very important thing about your mommy. She is so very proud of you little man, and she'll miss you forever.

Love,
Jenny-O

Cha, Cha, Cha, Changes...

I just got back from airport hell. Atlanta shut down due to a very bad rain storm yesterday afternoon, and as a result, all of the flights in the entire airport were either cancelled or delayed. Ick! I definitely could have thought of a better way to spend the time.

I was so looking forward to sleeping in my own bed after the awful hotel bed. Well, dear hubby decided to give me a brand new matress for my birthday. First change, upon reentry, that I perceived.

He also decided to put Meghan into her first official "big girl bed" while I was away. Another change that I missed.

Meghan went trick or treating for the very first time tonight while I was in airport hell...another change that I missed.

Some of my oldest friends called me while I was away. They were inquiring about our shared friend who went through the worst experience of her life while I was away. Another change that I missed.

I hate change right now. There is simply too much for me to handle right now. Is it too much to ask that if I go away for 2 days that when I return things are mostly the same? Guess it is, at least today.

Happy Birthday to me. I'm 34 today, and my only plan is to check in with aforementioned old friend to see how she is doing. Please pray for her. Thanks!

Jen

I'm Missing Halloween!

Tomorrow is our neighborhood association's night time trick or treat event. I'm currently in a hotel room in Miami on business, and won't be home until after the girls have hit the candy parade. I'm sad and frustrated about that, but had little choice in the matter. I told Charlie he had better take pictures or else. LOL

On Saturday, I turn 34. I'm not quite sure what that means to me. Since I've been so busy with a crazy project at work, I haven't really had time to think about it. The other day, I realized that I'd be alone for most of the day since Charlie and the girls will be attending a band concert for Kesa in Madison. About a month ago, I chose not to go to the concert because of my birthday, but I didn't realize that I'd be alone. In response to this realization, I cried. Before any of my friends and family fire off an email to me or call me about it, please don't. I'm not looking for an invitation to being distracted from the fact that I won't be with the most important people in my world on my birthday (for part of the day). I just wanted to let out how I feel here in my journal. I find that feelings fester if I don't communicate them, and well folks, there really are much WORSE things than getting some alone time on my birthday. I've gained perspective on the matter, and am most concerned for one of my oldest friends.

She is going through the worst possible events right now, and I can't share what they are. All that I can ask is for you all to pray for my pal. She needs every single one she can get to help her get through grief.

Jen in Miami, FL

Clueless Newbie Blogger Here

Today, I added a site meter to my blog and was feeling pretty proud of myself. That is until I went to republish my blog and accidentally stumbled upon unpublished comments that my visitors have been leaving for me. To those of you who left me comments, thank you so much! You made my day.

Gratuitous family picture:

I'm Tallin'!

This morning, Meghan was standing on our bed and having a good time with Char. Out of the blue, she says: "I'm tallin'!"

At first, I wondered what she meant, but then came my "ah ha" moment.

I said, "Oh! You are standing."

Gotta love the cute things kids say when they are learning to talk.

Pioneering Immunosuppression...woohoo!

http://www.post-gazette.com/pg/06205/708203-114.stm

Pittsburgh, Pa.
Monday, July 24, 2006

Less drug better for transplant survival
Immune system can accept donor tissue
Monday, July 24, 2006

By Anita Srikameswaran, Pittsburgh Post-Gazette

A protocol that allows children who get intestinal transplants to minimize the drugs needed to prevent rejection appears also to improve their survival chances.

The regimen avoids steroids and encourages the immune system to welcome the donor tissue, explained Dr. Rakesh Sindhi, co-director of pediatric transplantation at Children's Hospital.

"There's no question, as we look back at our data, that using less drug has been better for these patients," he said. "Today we'll often send patients home with barely about three to four medicines. It used to be there would be about 10 to 15 of them."

Dr. Sindhi will present findings today and tomorrow from four studies at the World Transplant Congress in Boston.

One of them reviewed 75 children who between 2002 and 2006 had transplants of small bowel either alone or with a liver at Children's. Three years after their operations, 84 percent were still alive.

Before transplant physicians implemented the new protocol, two-year survival rates were about 70 percent, comparable to international figures, Dr. Sindhi noted.

The new approach, which is now routinely used at Children's, is definitely better because patients live longer and need fewer drugs, he said.

It's based on a premise proposed by transplant pioneer Dr. Thomas Starzl, of the University of Pittsburgh, and others that creating the right balance between patient cells and donor cells will favor the development of immunological tolerance.

Near the time of transplantation, patients get a drug called thymoglobulin, which depletes the number of immune system T-cells that could attack the donor organ.

No steroids are given after the surgery, Dr. Sindhi said. "That's our way of starting the drug reduction process right up front."

Steroids can slow growth in children and lead to diabetes and hypertension, among other problems.

A standard dose of an anti-rejection drug called Prograf is administered initially, but after about three months, it is rapidly reduced. In general, the intestinal transplant patients require about half the amount of the drug than had been the norm, and no steroids, the doctor said.

The same approach is being used in the transplantation of other organs at Children's.

Liver transplant recipients might get to the point where they don't need the medicine anymore, or only need it every other day in minimal doses. The liver has a greater capacity to regenerate, so it can recover more easily than the intestine or kidney from mild rejection episodes, Dr. Sindhi said.

"If rejection occurs, we treat it the same as we always have," with steroids and more medicine, he said. But "using this approach, we've noticed that rejections are not any worse than before."

Renee Rosner's daughter Adelynn, now 4, got a liver transplant when she was 9 months old and weighed 13 pounds. The North Huntingdon girl had biliary atresia, in which the ducts that drain bile from the liver are obstructed.

Adelynn had the thymoglobulin protocol during her transplant, but did need steroids because of mild rejection.

"She was the classic steroid baby," her mother said. "She was chubby with the big moon face, which for us, believe it or not, was almost a relief because she had been so skinny."

But Ms. Rosner was glad when the steroids were tapered, and Adelynn no longer needs them. The child used to take a total of 7 milligrams of Prograf each day, and now takes 2 milligrams once a day. That will soon be reduced again, Ms. Rosner said.

"The goal would be the need for no immunosuppressor [drug] at all," she said. " Quite honestly, I would be very happy with every other day."

As the Prograf dose has come down, Adelynn is sleeping better, her mother said. And if she no longer needs the antirejection drug, she should also be able to stop taking other medications that counteract its side effects.

(Anita Srikameswaran can be reached at anitas@post-gazette.com or 412-263-3858. )

Asthma common in alpha-1 antitrypsin deficiency patients

Asthma common in alpha-1 antitrypsin deficiency patients
Aug 02, 2006 - Asthma is common in patients with alpha-1 antitrypsin deficiency (AATD) and is usually associated with chronic obstructive pulmonary disease (COPD), suggesting that patients with the deficiency should undergo allergy evaluation, say US scientists.

AATD contains a wide range of AAT phenotypes that confer varying susceptibility to obstructive lung disease and emphysema. The most common variant for homozygous severe deficiency is protease inhibitor (Pi) Z, giving the PiZZ phenotype.

Seeking to identify the prevalence of asthma and atopy in AATD individuals, Edward Eden, from Columbia University in New York, and colleagues sent a survey to 2418 individuals in the Alpha-1 Foundation Research Registry.

The 757 responses revealed that 44.6% had been diagnosed with asthma, while wheezing was reported by 76%. Common triggers were respiratory infections, activity and exposure to dusts, fumes, and allergens.

Dividing the patients into those with the PiZZ phenotype, those with the less severe PiMZ phenotype, and other phenotypes showed that the prevalence of asthma ranged from 20–25%, with wheezing significantly less common in the PiMZ group than in the others.

Of those with asthma, 83% of PiZZ individuals also had a diagnosis of COPD, compared with just 48% of those in the PiMZ group, the team writes in the journal Respiratory Medicine. Asthma was three times more prevalent as the only reported diagnosis in the PiMZ group than in the PiZZ group.

“Asthma is difficult, if not impossible, to distinguish clinically from COPD in those with established airflow obstruction,” the researchers write.

“Given the overlap between asthma and COPD in this population and the potential impact of asthma on forced expiratory volume in 1 second loss, evaluation of the wheezy patient with AATD should include allergy testing and aggressive treatment to reduce bronchial hyperresponsiveness.”

Respir Med 2006; 100: 1384–1391