Monday, November 27, 2006

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!

Friday, November 24, 2006

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]

Tuesday, November 21, 2006

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 ( 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.

Sunday, November 12, 2006

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!

Wednesday, November 08, 2006

November is Prematurity Awareness Month

Save Babies From Premature Birth

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

Tuesday, November 07, 2006


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."

"In here!"
"In the corner by the table!"
"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.


"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 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!


Damn it!