Thursday, February 21, 2008
Stem Cell Research and Crohn's
Roanoke Teen to Head to Chicago in Pursuit of Crohn's Disease Cure (from July 2003)
An insurance company, hospital and federal regulators have approved a Roanoke youngster with a severe intestinal disease to have an experimental stem-cell transplant that could cure or kill him.
Thirteen-year-old Jordan Fifer heads to Children's Memorial Hospital in Chicago later this month.
People ask him if he is scared or afraid of dying. He tells them he's not.
"I don't know why I am not scared. I'm just not," he said. "I'm incredibly eager. And I just know when I come back, I will be able to do things that I haven't been able to do for so long and that means a lot to me."
Like eat a piece of pizza and have the energy to play soccer.
Jordan, who this fall will be a freshman at Patrick Henry High School and the Roanoke Valley Governor's School for Science and Technology, was stricken with Crohn's disease at about age 10. With Crohn's, the digestive system comes under attack by the immune system. When the disease is active, it causes stomach aches, diarrhea, rectal bleeding, weight loss, fatigue and fever.
About a million Americans have Crohn's or a similar condition, ulcerative colitis, according to the Crohn's and Colitis Foundation of America. There is no known cure.
Jordan had tried without success to get relief through a variety of prescription drugs and other traditional therapies. His mother, Hope Trachtenberg-Fifer, learned about a Chicago medical team that has treated about a dozen Crohn's patients, adults and children, with a transplant of blood stem cells.
Jordan's health insurer - he's insured through his dad Gary's health plan - this week approved paying part of the cost for Jordan to have a transplant. He will be the youngest person treated so far.
Blood stem cells are the building blocks of blood inside the bones. Already, blood stem cell transplants correct disorders of the blood and disease-fighting immune system and repair damage to such systems caused by some cancer treatments, such as chemotherapy.
But until the transplant has been proved to address Crohn's, it is classified by the federal government as an experimental treatment. The U.S. Food and Drug Administration supports the ongoing experiment in which Jordan will participate and has approved methods to be used.
So within weeks, Jordan will leave for a three- to four-month stay in the Chicago area. He will be hospitalized only part of that time but must remain near the hospital for follow-up care. His mother will stay with him at a home for transplant patients and their families, from which Jordan and his Mom may move to an apartment.
Here's how the procedure works: Medication will draw stem cells from Jordan's bone marrow into his bloodstream for collection (he'll be his own stem-cell donor). High-dose chemotherapy will destroy his immune system. Then doctors will reintroduce the stem cells to his bloodstream. If all goes well, the cells will create a new immune system without the malfunction that afflicts Jordan today.
The procedure carries a small risk of death. Jordan's immune system may not regenerate, placing his body at serious risk of infection. He also could have an allergic reaction.
The Crohn's and Colitis Foundation of America, dedicated to education, patient support and fund raising for research, sounded a note of caution. The organization released a statement in which a member of its scientific advisory panel, Dr. William Sandborn of the Mayo Clinic, said he's uncertain the benefits of stem-cell transplants in Crohn's disease patients outweigh the risks.
Jordan's mother said all of about a dozen people who have had the procedure have been helped. The average Crohn's patient does not experience severe symptoms and does not need a transplant, she said. However, Jordan's Crohn's, because it is uncontrolled, actually poses a much higher risk of death than the procedure, she said.
Jordan has been hospitalized numerous times. He takes 33 pills a day. He suffers from bouts of digestive system bleeding that sometimes make it necessary for him to have a blood transfusion. His disease has stunted his growth and kept him from school and social activities. Yet, the youngster is getting good grades, played xylophone in his middle-school band and volunteers.
"Patients like Jordan, like my child, who have volunteered for this study are very desperate patients who are looking for light at the end of the tunnel and, it seems, have found it," Trachtenberg- Fifer said.
First Patient to Get Stem Cell Treatment for Crohn's in Remission
By Peggy Peck WebMD Medical News
Reviewed by Gary D. Vogin, MD
Aug. 10, 2001 -- Joy Weiss treated herself to a Big Mac for lunch on Friday and then considered whether she should top off the meal with a salad, some fruit, or both. For most 20-somethings, that doesn't sound like an extraordinary lunch choice, but for Weiss it's a miracle meal.
The miracle in this case is a controversial, experimental medical procedure that involves stem cells harvested from a patient's own bone marrow.
Ten weeks ago, Weiss became the first person to undergo the stem cell infusion for treatment of Crohn's disease, a condition in which the body's immune system attacks the patient's digestive tract. On Monday, researchers at Chicago's Northwestern Memorial Hospital completed a second such treatment in another Crohn's patient. The second patient, reportedly a 16-year old male, has requested anonymity, says Richard Burt, MD, lead researcher in the pilot study. Burt says, however, that the second patient is doing well.
For years, Weiss did not know a single day without pain, the gut-wrenching pain caused by Crohn's disease. "Until I was 19 I could never get my weight up above 90 pounds," says the 22-year-old Weiss. Dairy foods, salad, fruit, nuts, fried foods -- all were dietary no-no's for Weiss, who was diagnosed with Crohn's disease when she was 11.
Over the years of treatment for the condition, Weiss suffered through as many as 10 daily attacks of painful diarrhea characterized by watery, bloody stools.
Treating the Crohn's symptoms required the powerful steroid prednisone, which helped quiet the inflammation caused by the disease but also weakened other tissues in her body. Moreover, years of intestinal disease plus steroid therapy impaired her body's ability to absorb calcium, so she has developed osteoporosis, the bone-wasting disease normally associated with old age.
Two years ago, Weiss' doctor began using IV tubes to deliver "night feeds so that I could get some nutrients." Her gastroenterologist recommended her for a colostomy, a procedure in which a large part of the colon is removed and the patient wears an external bag for waste. But after examining her, "my surgeon said that although my body was ready for a colostomy, I wasn't ready psychologically, so he said he would look for other alternatives."
The surgeon turned to the Internet, and there he found an article about Burt's proposal to treat Crohn's disease with an experimental procedure that required a stem cell transplant, using cells harvested from the patient's own bone marrow. This type of transplant is used to treat leukemia and other cancers.
Burt and his co-investigator Robert Craig, MD, had been waiting for about three years for the "right patient for this procedure," says Craig, a professor of medicine at Northwestern University Medical School.
The pilot study in which Weiss was the first patient will eventually include 10 Crohn's patients who have "failed all other accepted therapies," says Burt. Craig tells WebMD the patients not only "will have failed all other therapies, but they also must convince me that they are willing to take the risks associated with stem cell transplant."
Stem cell transplant is an experimental procedure that definitely carries its own risks. First, the cells are harvested from the patient's bone marrow, and then the patient is treated with powerful chemotherapy drugs, which are used to destroy the patient's immune system. After the immune system is destroyed, the patient's stem cells are injected back into the body and the patient is kept in a sterile environment for two weeks so that the "new" immune system can develop. During this time, any infection can pose fatal risks.
Because Crohn's disease is usually not fatal, some researchers are questioning the advisability of treating the disease with such a risky procedure.
In a statement released Thursday, the Crohn's and Colitis Foundation of America said "We are not certain that the benefits of stem cell transplants in Crohn's disease patients outweigh the risks. ... Scientists have yet to determine whether stem cell transplant can initiate a long-term remission in people with Crohn's disease. In addition, the potential benefits of this therapy must be weighed against the risk of infection. While Crohn's patients have an altered immune system, researchers have not yet determined whether Crohn's can be qualified solely as an autoimmune disease. Until those questions are answered through carefully monitored, long-term clinical studies, stem cell transplant in Crohn's disease patients remains an investigational therapy."
Craig tells WebMD, "I agree with the CCFA. Believe me, a patient has to convince me that this is the absolute right thing for him or her." He says that he worries "about the possibility that I will lose a patient to this therapy."
The type of caution expressed by Craig is well placed, says Richard MacDermott, MD, head of gastroenterology and immunology at Albany Medical College in New York. "This is obviously a truly investigational procedure at the very beginning of the investigational ladder. It has a long, long way to go," MacDermott tells WebMD.
"I don't personally know the [rate of sickness and death] associated with stem cell transplant, but it has got to be significant," says MacDermott, who is a trustee of the Crohn's and Colitis Foundation of America.
Burt says the procedure "wasn't done in a cavalier or relaxed manner -- the procedure was approved by the FDA." He says, too, that the chemotherapy used in his stem cell protocol is not as toxic as earlier stem cell transplant experiments. "The only complication that we had was a two-day fever," says Burt, who adds that tests done during that two-day period turned up no evidence of infection.
From her perspective, Weiss says she underwent two cycles of chemotherapy and neither was "as bad as my worst days with Crohn's." She says that she started feeling better "almost right away. All the pain didn't leave but it started getting better right away. This is the first time I have had a Crohn's remission in 11 years."
Weiss spent about two and half months in Chicago undergoing pretreatment screening, treatment, and immediate follow-up. She is expected back in Chicago on Aug. 18 for a follow-up exam and then will return again at six months, nine months, and 12 months for follow-up. After 12 months, "I'll go back every year for five years," says Weiss. Craig says that it will take at least five years to confirm a true remission of disease.
Meanwhile, at her home in Mariaville, Maine, population 500, Weiss is enjoying the "first summer of my life." Always interested in horses, Weiss is anticipating applying to college to study "equine science. I have a mare here and now I am able to go out and walk the mare. It is a miracle."
Stem Cell Transplants Cure Crohn's Disease
Another advance in regenerative medicine is reported in the Reno Gazette-Journal. Ten sufferers of the deadly Crohn's disease have been cured by stem cell transplants that regenerate the damage to their intestines and immune system. The article focuses on the young man who will hopefully be number 11 and live to see a full life. This is the sort of amazing application of stem cell medicine, like recent advances in regenerating normally fatal heart damage, that we hope will become commonplace. Being able to regenerate any part of the body in this fashion will lead to large gains in healthy lifespan.
More about Stem Cell Research, Stem Cell Transplants and Crohn's Disease:
Stem Cell Transplant
What is a stem cell transplant?
The stem cells corresponding to each part of the body provide instructions for how to grow that part. For Jordan's kind of stem cell transplant, bone marrow was drawn from his hip bone using a long needle. The stem cells were separated out and frozen. Jordan's immune system was then partially destroyed by high-dose chemotherapy, and his stem cells were reintroduced to his body in the hopes that they will multiply and build a healthy immune system.
Most stem cell transplants of this type are autologous, meaning that the patient is both the donor and the recipient. Only cells are transplanted; the procedure does not involve the replacement of any organs or other body parts. Although the transplant itself does not involve surgery, Jordan has had many surgical procedures to implant and remove ports and catheters used to inject and draw fluids and drugs.
How often are stem cell transplants performed? What are the chances for success?
Although about 2.5 million people worldwide have had stem cell transplants for various diseases (usually certain cancers), only between 15 and 20 people have had stem cell transplants to treat Crohn's disease. Jordan was the youngest patient in the United States -- and the first at Duke University -- to undergo the procedure as a treatment for Crohn's disease.
Each patient who has previously had a stem cell transplant for Crohn's disease has experienced almost complete remission. Reports from the patients and their medical teams continue to be very encouraging. The patients have experienced significant improvements, and many have been able to return to lives essentially free of the symptoms of the disease. Many have been able to dramatically reduce or eliminate their dependence on daily medication, and the resulting side effects. The younger patients have experienced growth spurts, as their bodies are relieved of the stress of the disease and receive proper nutrition.
When and where was Jordan's transplant performed?
Jordan's transplant was performed on June 2, 2005, by a medical team at the Pediatic Bone Marrow and Stem Cell Transplant Program at Duke University Medical Center. This team includes hematology and oncology specialists, gastroenterology specialists, and other support staff. Jordan and a parent travelled to Duke on April 2, 2005, and returned home to Roanoke, Va., on July 31, 2005.
How long does the stem cell transplant take?
The transplant itself (the reintroduction of Jordan's previously harvested stem cells to his body) took only 30 minutes, but the entire transplant protocol took about four months. During that time, Jordan lived in the hospital and in an apartment near the hospital. As his health permitted, he participated in distance learning and received homebound tutoring to keep up his high school studies. It will take about one year for Jordan's immune system to completely rebuild itself. Jordan will also be monitored by doctors in Roanoke, and at the treatment site, for routine checkups.
What risks and side effects are associated with a stem cell transplant?
The primary side effects of the transplant come from the chemotherapy and other drugs involved in the protocol, and not the transplant itself. Jordan has experienced nausea, loss of appetite, and hair loss. Because Jordan's immune system was partially destroyed, he is at an increased risk of infection. To guard against this, he was hospitalized in a special room with a positive air pressure system and high efficiency particulate air (HEPA) filtration. Even after returning to Roanoke, his exposure to people and places is restricted. Although all medical procedures carry some risk, and stem cell transplants carry a higher risk of complications than some other procedures, the risk of death from an autologous stem cell transplant is still extremely low.
How much will the stem cell transplant cost?
For more information about the costs associated with the transplant, see About the Fund.
Aren't stem cell transplants very controversial?
The political controversy surrounding stem cells relates to the use of animal or fetal tissue to clone embryos for research. In Jordan's transplant, like in most stem cell transplants of this type, Jordan received his own stem cells.
Tuesday, February 19, 2008
But 10-year-old Jacob Kaufman admits that if there’s one thing that leaves him excited these days, it’s not the trips or any honors but the fact that he may have turned a corner in battling a rare form of Crohn’s disease that made him miss school for nearly six months.
He’s not out of the woods yet. But after undergoing so many tests, procedures and surgeries, Jacob, a fifth grader at James L. McGuire School, is at the point where some doctors at Hasbro Children’s Hospital believe his disease is in remission and that he may be ready for another try for a reverse colostomy that would allow him to live a normal life once again.
In part because he has shown so much tenacity, and even courage, the hospital has named Jacob its first-ever representative to the Children’s Miracle Network Champions Across America program, which honors children who have triumphed despite severe medical adversity.
The network is both a fundraising tool for the nation’s children’s hospitals and a way of providing inspiration to children and their families.
Jacob shares his time between two households: with his father, O. Brian Kaufman, who lives on Smithfield Road with his companion, Michelle Niestrepski; and his mother, Joanne Kaufman, who lives in Pawtucket with her companion, Edward LaRose.
As Jacob and his family tell it, his story began 13 months ago when he woke with a fever that wouldn’t go away, accompanied by severe pain and constipation such that he could hardly walk. Only after a CAT scan did doctors discover that he suffered from a rare form of Crohn’s disease, in which a high white cell count was fooling his body to attack tissues in the intestine, ultimately leading to an abscess that was strangling his rectum.
He was in and out of the hospital 81 days as doctors employed different strategies to reduce the infection. But he was an unusual patient in another way: the 10-year-old read everything he could about Crohn’s disease, became informed on all the medicines he was taking, and made it clear he wanted to be one of the decision-makers.
“Since the beginning he’s been part of every conversation with the doctor,” recounts his father, Brian, an instructor of English at Quinebaug Valley Community College in Danielson, Conn.
Indeed, battling Jacob’s disease has been a family affair. During the week, Joanne, who works at Regine Printing in Pawtucket, and Edward, who was temporarily unemployed when the company he worked for moved to Cleveland, took turns standing watch at the hospital at nights and during weekdays; while Brian, whose health insurance was paying the bulk of the nearly $1 million that the treatments were costing, and Michelle, who was then nearing completion on her doctorate in English at the University of Rhode Island, took over the weekends.
When the family realized that one of the operations fell on the same date as the opening of the new Harry Potter movie, which Jacob wanted to see, the five resolved the dilemma by going to a special midnight show, just a few hours before Jacob was slated to report to the hospital.
The parents recall other moments, such as when Dr. Jason Shapiro of the Hasbro staff read chapters of a newly released Harry Potter book for 2½ hours while Jason was undergoing an MRI. And when Jacob complained “what did they do to me,” Dr. Richard G. Gillerman saw to it that hospital staff would no longer put a catheter on him unless Jacob approved. Jacob was also the one who decided whether he should be injected with a new drug, Remicaid, that had been effective for 70 percent of patients but carried risks. As Jacob explained yesterday: “I just decided to try it because I didn’t think it could get worse than I already was.”
Last September, just four days after being injected with the new drug in a four-hour procedure, Jacob was feeling great, so much so that he was ready to go back to school.
Since then he’s been a straight A student, and taken up the clarinet and playing with rubber swords. He’s gained 10 pounds.
The hospital originally wanted to honor Jacob with a celebration today at his school, but school officials rejected that idea saying it would have entailed too many complications. So the hospital turned to Wal-Mart, which is giving Jacob a $1,000 shopping spree at its Coventry store at 10 a.m. today.
There are other events slated for next month — a celebration with other Children’s Miracle participants at Disney World, followed by a charter flight to Washington.
Wednesday, February 13, 2008
"We are very encouraged by the findings of this study and look forward to larger prospective studies," says researcher Konstantinos A. Papadakis, MD, with the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center in Los Angeles, in a news release. His paper appears in the current issue of American Journal of Gastroenterology.
Crohn's disease Crohn's disease is a serious chronic and inflammatory disease of the intestinal tract, causing diarrhea, cramping, stomach pain, weight loss, and in some cases rectal bleeding. These symptoms wax and wane, with periods of active inflammation and disease followed by periods of inactivity. There is no cure for Crohn's disease, but Remicade has helped to greatly reduce symptoms of this lifelong disease.
Remicade, a drug that works by blocking a part of the immune system know as TNF, is currently the only FDA-approved "biologic" treatment of this kind for the treatment of Crohn's disease. The drug lessens the symptom flare-ups and helps keep people in remission for long periods of time. It also helps people avoid developing fistulasfistulas, a common complication in people with Crohn's disease. Fistulas are openings of the intestine into other organs or on to the skin, such as around the anus -- which can seriously affect quality of life, and often requires surgery.
Crohn's Disease vs. Humira
In his study, Papadakis tested Humira, a similar drug that suppresses the immune system and is FDA-approved for treatment of rheumatoid arthritis.
His study involved 13 patients with Crohn's disease. All had been taking Remicade, but were no longer getting any relief from it. In the six-month study, they got an initial 80-milligram injection of Humira, then 40-milligram injections every two weeks. Researchers tracked their symptom relief.
Of the 13 patients, seven had complete symptom relief, four had partial relief, and two got no relief. Six of the patients required a boost in their dosage to maintain symptom relief.
Almost three quarters of the patients (73%) were able to discontinue or significantly decrease their concurrent dose of steroids.
All patients tolerated Humira without any allergic reactions; two patients had a skin reaction at the injection site.
Overall, the study shows that Humira is a strong option for Crohn's disease patients -- when Remicade no longer works, writes Papadakis.
Remicade's side effects include:
A rare but deadly liver reaction
Serious, even fatal, infections like tuberculosis
Increased risk of certain types of cancer like lymphoma
Increased risk of an autoimmune disorder such as a lupus-like syndrome
Humira's side effects include:
Serious, even fatal, infections like tuberculosis
Increased risk of certain types of cancer, like lymphoma
Increased risk of an autoimmune disorder such as a lupus-like syndrome
Monday, February 4, 2008
Tysabri Approved for Crohn's Disease
TUESDAY, Jan. 15 (HealthDay News) --
Tysabri (natalizumab) has been approved by the U.S. Food and Drug Administration to treat moderate-to-severe Crohn's disease in people who haven't responded to other therapies.
Tysabri, made by the Ireland-based drugmaker Elan and Massachusetts-based Biogen Idec, was approved in 2006 to treat relapsing multiple sclerosis.
The drug has a boxed warning of increased risk of progressive multifocal leukoencephalopathy (PML), a viral infection affecting the brain that could cause severe disability or death, the FDA said in a statement. Anaphylactic reactions and liver injury also have been reported in some users.
Crohn's patients prescribed the drug will be enrolled in a restricted distribution program called Crohn's Disease-Tysabri Outreach Unified Commitment to Health (CD-TOUCH). Under the program, physicians must evaluate Crohn's patients using Tysabri after three months and should discontinue use of the drug if there is no improvement, the FDA said.
Crohn's is an incurable bowel disease with symptoms that may include diarrhea, fever, rectal bleeding, malnutrition, narrowing of the intestines, cramping, and abdominal pain. The disease, affecting more than 1 million people worldwide, can also lead to abnormal connections called fistulas from the intestines to the skin or internal organs.
More about Tysarbi:
Elan Corp., Ireland's biggest drugmaker, and partner Biogen Idec Inc. won U.S. approval for the use of their multiple sclerosis medicine Tysabri as a treatment for Crohn's disease.
The Food and Drug Administration issued its determination in an e-mailed statement today. Elan and Biogen said in a separate statement that they expect Tysabri to be available to Crohn's patients by the end of February, once an FDA-approved plan to minimize risks of the drug is in place.
The companies are trying to expand the use of the medicine, which brought in $93 million in the third quarter. Tysabri is taken by about 21,000 MS patients under prescribing restrictions because of a risk of rare, fatal brain infections. Similar rules will be used in treating Crohn's disease, a chronic inflammation of the intestines that affects about 1 million people worldwide.
The approval is ``an important step in the armamentarium for treatment but one that carries extreme risks,'' said Joyce Korvick, deputy director of the FDA's office of new gastroenterology drugs, on a conference call with reporters.
Other therapies for Crohn's include Abbott Laboratories' anti-inflammatory medicine Humira, which exceeded $3 billion in global sales for the first time in 2007, Abbott Chief Financial Officer Thomas Freyman said on Jan. 7.
Dublin-based Elan discovered Tysabri, and is developing the medicine as a Crohn's treatment. Its partner Biogen, based in Cambridge, Massachusetts, lost more than $5 billion in market value in December after announcing it failed to find a buyer and planned to remain independent.
Biogen rose 90 cents, or 1.5 percent, to $59.92 at 4 p.m. New York time in Nasdaq Stock Market composite trading. Elan's American depositary receipts, each equal to one ordinary share, rose 10 cents, or less than one percent, to $24.86.
Pulled From Market
Tysabri was the best hope in a decade for MS patients when it was approved in November 2004. It was pulled from the market three months later because of links to a neurological disorder called progressive multifocal leukoencephalopathy, or PML. Three patients contracted the disease, and two died.
About 14,000 patients have been treated with Tysabri since it was returned to the market as a multiple sclerosis drug in July 2006. No cases of PML have been reported. An advisory panel to the FDA voted 12-3 last July to recommend approval of the added use for Tysabri for Crohn's disease, with restrictions to reduce the risk of infection.
In October, the FDA extended its review. A month later, European regulators rejected an appeal by Elan and Biogen of an earlier decision that the product not be approved and marketed for Crohn's.
Former University of Worcester student and newly-qualified teacher Melanie Gough, aged 24, who was six months' pregnant with Luie, died after surgery for Crohn's disease, which doctors failed to diagnose, despite four earlier visits to hospital. Richard Gough claimed in court that his daughter, who was due to marry partner Phil Adams before her illness, would not have died had Gloucestershire Royal Hospital staff acted sooner. Mrs Gough, who fell pregnant in October the previous year, was treated throughout January 2007 for severe vomiting, dehydration and weight loss.
But she was discharged at the end of the month, after doctors wrongly diagnosed an unusually severe form of morning sickness, or hyperemesis gravidarum.
When she was readmitted at the end of February, after her symptoms worsened, an expert consultant immediately diagnosed her with Crohn's disease and ordered an operation to remove part of the colon.
She died on March 6 last year after she was found to be suffering from a septic infection.
Mr Gough told Gloucester Shire Hall that his daughter was one of five children and active in her local community in Longhope, in the Forest of Dean, Gloucestershire.
He said: "She was a real home-body, and very close to her mother. They did everything together. When it was time for her to go to university we found her a place close to home where she could travel back and forth every day. pregnacy and crohn's
"She went to Worcester university, stuck it out and got a good degree. She didn't get a teaching job straight away, and worked in various pubs to support herself. She also got supply teaching work.
"She had been with her fiancee Phil for four years, and they were due to get married in April. She lived a very happy life and was very involved with her local community. She kept two horses in fields were she lived."
She fell pregnant on October 1 2006, and had the couple had named their son Luie.
Mr Gough said she had enjoyed good health, apart from being diagnosed with irritable bowel syndrome at university.
But after Christmas she began to suffer with projectile vomiting, constipation and diarrhoea, he told the hearing. Despite several trips to the maternity unit with ongoing sickness and rapid weight loss, Mr Gough said that nurses urged her to put up with the pain.
He told the court: "They said, 'Pull yourself together. This is part of pregnancy. You'll get used to it'."
It was not until February 15 that she was diagnosed with Crohn's disease when Professor Hugh Barr, a consultant gastroenteritic surgeon, became involved in her care.
Mr Gough said: "They realised there was something seriously wrong. There was 100 per cent obstruction in her bowel and it was so advanced that the intestine had become stuck to the abdominal wall.
They said, 'Pull yourself together. This is part of pregnancy. You'll get used to it.'
Richard Gough, father But after the procedure she again became seriously ill and was treated in hospital again on March 6 where it was clear that she was terminally ill.
Mr Gough said: "After they injected her through a tap her eyes closed and her chest started heaving. The doctor asked her to open her eyes and wake up. We were in shock.
"Phil and me were asked if we would prefer to save Melanie or the baby. We both agreed that Melanie should be our priority.
"Shortly afterwards, the doctor said she had suffered a second cardiac arrest and that the best doctors in the country were working on her. They said she was critical and didn't hold out much hope. "After she died she was put into an office full of papers.
"Our family are absolutely devastated by the loss of our daughter and her unborn child. We feel her death was unnecessary and completely avoidable.
"We feel that had her illness been treated earlier she could have been saved. There was at least half hour delay before they made any sort of attempt to do anything. We are not happy about her treatment before and after the operation."
Consultant obstetrician and gynaecologist, Mark Whittaker, who looked after Ms Gough throughout her pregnancy said that her symptoms bore all the hallmarks of morning sickness and that she had begun to improve. He said: "I thought she had emesis gravidarum (morning sickness). We see patients on a daily basis with pain and vomiting - it is very common in the first 16 to 20 weeks of pregnancy. But we thought there might be some other course, that's why a follow up was arranged. "We felt she had hyperemesis gravidarum and we treated the condition we felt was affecting Ms Gough.
Mr Whittaker said: "I think that it was extremely difficult to identify the cause of her symptoms. I think she was seen by four experienced obstetricians and four experienced consultant surgeons, proving how difficult it is to diagnose this condition."
The coroner said: "I understand that it is difficult to diagnose because a woman's body produces various hormones that act as immuno-suppressants."
Matthew Barnes, the family's barrister said: "She had had four admissions for symptoms that were getting worse and worse..."
Mr Barnes said: "The family want to know why more wasn't done to find out what was going on."
The court has yet to hear what part, if any, the delayed diagnosis played in Ms Gough's death.