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neurological resident todd thompson, left, and neurosurgeon douglas kondziolka, right, attach a device called a stereotactic frame to the head of richard mulvihill. neurosurgical resident todd thompson controls bleeding from a scalp incision durin

by:Cailong     2019-07-17
neurological resident todd thompson, left, and neurosurgeon douglas kondziolka, right, attach a device called a stereotactic frame to the head of richard mulvihill.         neurosurgical resident todd thompson controls bleeding from a scalp incision durin  -  clear plastic film
"I feel very good," said Moon Hill, 56 . " He was a Vietnam veteran who almost lost a leg after stepping on a mine.
Nearby, the doctor is ready to screw the hard metal frame into his skull.
Install a metal arc on the frame to form a device that looks like a six-point meter, the navigation instrument used by sailors since 1700
Surgeons will also use frame navigation to accurately guide a long, thin needle to a small part of the brain injured by a stroke.
"I can't wait until they do that," said moonhill . ".
Three years ago, MUVI Hill suffered a stroke that left him paralyzed on the right and spoke incoherent.
Since then he has recovered most of what he has lost: he can walk and he speaks clearly most of the time.
But his right hand is of little use, and he is troubled by his memory.
When he heard that Pittsburgh was testing experimental treatment for stroke patients, he made up his mind to get it.
When the four screws secure the frame firmly on his head, the nurse slides Mulvihill onto the table of the CT scanner.
He is awake but does not move inside the tubular scanner and it takes dozens of crossessectional X-
Ray images of his brain
"This little black hole here is the beginning of it.
"Kondziolka points to a small black spot on the left and then to a fine gray line on the undamaged right side of Mulvihill's brain.
"This is an internal capsule," he said . " An important nerve fiber bundle that enters the spinal cord down from the right frontal lobe of the brain to control the movement of the limb on the other side of the body.
On the left side of the MUVI Hill brain, it should look like a mirror image on the right, and the thin gray line is not there.
"It's a small stroke, but in a very critical position, right in the motor fibers on the right side of the body," Kondziolka said . ".
He clicks on more pictures to explore the boundaries of the strokes.
He picked up the computer's mouse and marked an "X" in a place inside the damaged brain tissue knot ".
This will be the goal.
Here, surviving neurons are struggling to recover lost connections, and surgeons will sow extraordinary cells that Richard moonhill hopes will give him the use of his right hand and repair his wrong memory.
Study testing the safety of treatment the only conclusion Kondziolka has drawn from a small study starting in last June is that the implantation of these cells into the brain of stroke patients does not seem to make them worse.
Although three of his early patients thought the treatment made them better, the harvest was small and barely noticeable in objective neurological tests.
This does not bother Kondziolka, who is most concerned about the possible complications of implant surgery ---
Bleeding, infection, rejection of foreign cells, and even deterioration of existing brain damage.
The only common side effects so far are csa-related fatigue, a drug that patients take eight weeks after surgery to prevent the immune system from repelling implanted cells.
"We are very happy so far," Kondziolka said . ".
Sending cells during a rescue mission Shirley Wallace opens one of the waist of the lab
High liquid nitrogen freezer--
Maintain a constant temperature of minus 238 degrees-
Take out a small plastic bottle sealed.
She put it in a warm one
The water takes a bath, gently sweeps away, and defrost the tiny volume of liquid inside for long enough.
The tubes hold millions of living cells living in liquids that protect their fragile membranes from damage during freezing and thawing.
Wallace opens vials in a special work area called "hood" that is designed to keep precious specimens from bacterial contamination.
She rinses the cells several times to remove the protective solution and then adds a special dye, Taiwan Pan blue, to the solution.
Living and healthy cells do not accept dyes and remain colorless.
Those who die or are about to die will turn blue.
The technician uses a fine dropper called a liquid transfer tube to squeeze samples of suspended cells onto the glass plate for counting.
By observing with a microscope, calculate the number she sees on the grid and multiply it by the total, she will be able to estimate that there are millions of cells in the vial.
More than 50% of the cells she sees are colorless.
Otherwise, the vials will be discarded and a new vial will be thawed.
Enlarged 200 times under a microscope, the cells look round and a bit uneven, like tiny clear scones.
They tend to come together in groups from several cells to 20 or more.
Some have delicate, tornado-like growth that protrude from the surface.
They seem to be exploring the surroundings.
The cells came from the plant of Layton BioScience, a small California company.
However, their ancestors came from a 22-year-
More than 20 years ago, an old man in a New York hospital
This is a strange cancer called embryonic cell tumor.
This tumor usually contains a mixture of a cell type that behaves very similarly to the developing embryo.
After years of research and repair of these tumor cells, biologists in Philadelphia have isolated a group of cells that can be induced into normal adult nerve cells or neurons.
When treated with the right chemicals, they turn themselves from constantly breeding cancer cells to cells that stop breeding and send out finger spikes like nerve cells used to make connections with other cells
They also made the same structure and surface proteins as normal human neurons.
This is a very promising finding because, unlike ordinary neurons, these tumors
Derived cells can multiply indefinitely in the laboratory to ensure a permanent supply.
In ten years of experiments in several animals, these cells have been working like neurons and have never returned to their original cancer cell status.
The cell will enter the brain of Richard moonhill.
Cathy Trump, chief technical expert, said, "The people in the lab, we are always thinking: there are neurons in it, and they are talking to each other.
Do they know they're in there?
Memory is bad.
"One of my sheep [had]died.
I don't remember if it was buried or nothing.
I was doing something stupid that night.
I asked my wife, "What do you do with an oven ? "
The next morning he choked with a sip of coffee and when Karen moonhill looked at him she saw something wrong with his face.
He was able to walk into the emergency room, but the damage deepened over the next few hours.
He can't move his right.
"He can speak, but you can't understand it," recalls Karen moonhill.
"He remembers the day he first moved his big toe on his right foot.
He spent nearly two months at the VA hospital, then went home and started physical therapy three days a week.
"It's not enough for me," he said . ".
"I want to do everything.
"These days, MUVI Hill exercises every day at the YMCA and uses as many as 23 fitness machines as possible.
He made it clear most of the time.
But when he is angry, words seem to throw him away.
"I can't yell at anyone because I messed up what I wanted to say," he said . ".
"My memory seems to bother me with this leg and arm.
I can accept it.
But memory is not good.
"A needle in the brain. The first set of CT images showed horizontal slices of the brain through moonhill from top to bottom.
The second group shows the coronary View--
Looking at MUVI Hill's face
Cross his head from front to back.
The third group of slices passes vertically from left to right.
Douglas konzoka marked his target on three sets of images with a computer.
He then calculates the exact digital coordinates needed for the guide needle.
These numbers specify the settings that he will use on the metal arc in order to arrange his needles in the appropriate position and angle.
"Our coordinates are only measurements of the actual distance starting from [arc]
"He said.
The needle will be fixed on the metal arc--
Part of a navigation instrument called a stereo frame--
This is attached to the head of MUVI Hill.
Once Kondziolka selects his route using a CT image, the stereo frame will ensure that he follows it completely.
First, the stable needle, a fine metal needle about 6 inch long, will pass through the gray outer layer called the cerebral cortex and pierce the top of the left half of the brain of MUVI Hill.
It will pass through the potential nerve bundles that form white matter and reach down to the basal section, a collection of nerve cells deep in the brain that helps control and coordinate movement.
The needle is hollow with a removable metal core inside.
Once Kondziolka is in place, he will take out the core and push it through the outside with a finer needle into the damaged internal capsule or nearby.
Through this needle, he will inject cells.
During each passage of the needle, the patient received a total of 2 million cells, which were injected in three different locations along a track about half an inch long.
Patients in the study were randomly assigned to obtain a needle pass (
Three shots in total)
Or three needles (
A total of 9)
So that researchers can know more about whether it is better or not.
Kondziolka finished his calculations and stood up and walked into the operating room.
Mulvihill is invisible under the green curtain, except for a scrubbed square skin on the top of his head, which is covered with a transparent plastic film.
He is fully awake and connected to the display, which shows a continuous reading of his pulse, blood pressure and arterial oxygen levels.
Li Meng, an anesthesia teacher, stood by him and stared at the monitor.
On a long green Street
Neurosurgeon Dan Harrold and James Faybik are laying a range of needles, clips and other devices.
Debbie Jennett, a mobile nurse, is helping them.
Everyone is wearing dresses, gloves, masks and hoods.
"Do you have a special sleeve for my Pittsburgh cell transplant?
"Kondziolka asked Jennette. She laughs.
He explained that he had to have an instrument specifically designed to inject cells.
"I don't want to call it Kondziolka.
This is a stupid name.
Kondziolka and Thompson put metal arcs on the frame.
Kondziolka took a pen and marked a position on a plastic film covering Mulvihill's shaved skin.
Thompson injected some local anesthetic on his skin.
Then he took the scalpel and made an inch. long incision.
The surgeon worked quickly, spread the skin with a retractor, and used an electric set to close the tiny bleeding blood vessels.
They pass through a layer of connected tissue galea, revealing a shiny white skull.
Then they open an electric drill with a blue metal handle, about halfinch bit.
"You will hear a little clicking," Kondziolka told Mulvihill . ".
When the drill makes a sound, the powder bone flies in the fine clouds to form a neat round hole in the skull.
The surgeon cuts the hard spine membrane with a long and thin blade, which is the hard shell of the brain.
Kondziolka then grabs the stable needle and now locks it on the metal frame and slowly pushes it into Mulvihill's brain at an angle specified by his coordinates.
"How are you, Richard? ""Fine. ""Good man.
"Shirley Wallace walked into the operating room with a small, sealed plastic tube.
She opens a tube, sucks some liquid containing cells into the transfer tube, and then transfers the liquid and cells to the vials where they can be ready for Kondziolka
Kondziolka and Thompson have pushed the stable needle into an inch-and-a-half range of the target.
Thompson pulled out the inner core and in its position, Kondziolka inserted a longer, finer needle he would use for the injection.
He gradually advanced in the last inch and a half, while walking and checking in with Moon Hill.
"How are you, okay? ""Great.
"Now Kondziolka takes out the cells in the vial, puts them in a fine glass syringe and screws the syringe into the hub of the needle.
He pressed the piston very slowly, pushing the cells into the brain of moonhill.
"How are you, Richard? ""Just fine.
"After a few minutes, the surgery is over, which is the main cause of disability in adults.
Once the needle is taken out, the surgeon removes the arc from the metal frame.
Thompson sprayed the sterile saline solution into the wound and gently applied the exposed skull with gauze.
The doctor closed the galea with three absorbent stitches and then closed the skin with nylon stitches.
The nurse moved Mulvihill back to the CT scanner to take post-operative images.
Judging from Mulvihill's off-the-shelf response during surgery, Kondziolka was confident that everything was going well and there was no sign of bleeding on the postoperative CT scan.
Kondziolka has been a neurosurgeon at the University of Pittsburgh Medical Center for 10 years, specializing in "minimally invasive brain surgery": fine surgery for tumor biopsy, nerve injection, Parkinson's disease, all of this is done with a CT scanner and a stereo frame via a fine needle.
It is this technical expertise that has attracted the California company Layton BioScience to obtain a laboratory production license.
The growth of nerve cells is a potential treatment.
About four years ago, company executives approached Kondziolka of the University of Pittsburgh and his colleagues, saying: "We have these cells.
What can we do with them?
Doctors in Pittsburgh believe that testing these cells is a way to treat a variety of nervous system diseases.
Because once the damage occurs, it will stabilize and affect specific areas of the brain.
"There is no medicine," Kondziolka said . ".
"There is no hope.
You can see this problem in the scan.
This is very different from Parkinson's or Alzheimer's, where you can't see the problem.
"There are also a lot of enthusiastic patients here.
Stroke is the main cause of adult disability, affecting 700,000 Americans every year.
Almost half of the survivors are permanently disabled.
To Kondziolka's knowledge, the University of Pittsburgh is the only medical center in the world to test nerve implants to treat paralysis caused by stroke.
More than 2,000 stroke patients from around the world contacted him and asked him to participate in the study.
They emailed him. mail. They call.
Their doctor wrote.
The tables and counters outside Kondziolka's office are filled with manila envelopes containing medical records and CT scans of people who want surgery.
Many people who meet the initial admission criteria will travel to Pittsburgh for two separate trips, examined and tested by a group of neurologists who will choose the best candidate.
Only a few people can meet the surgeon.
"They went on strike themselves," Kondziolka said . ".
"They are strong.
There are a lot of things in their lives that I can't see.
"A rare cancer, Peter W, a cell biologist, back in 1984.
Andrews found out that he could use vitamin A acid (
Chemicals related to vitamin)
To induce the conversion of embryonic cancer cells into neurons, no one imagined the possible treatment that would lead to a stroke.
"In those days, it was really too early to" consider nerve cell transplants, "Virginia M recalls. -Y.
Lee, a neuroscientist, worked with Andrews in Philadelphia to study the cells.
Andrews, now a professor at the University of Sheffield in the UK, believes that this new cell line is not so much a treatment as a research tool.
He wrote in an email: "These cells are clearly an important tool to study how nerve cells are produced during embryonic development, and perhaps how nerve cells regenerate
Email reply to the reporter's question.
"However, this is a question of speculation and medical ethics. . .
Such a tumor
It is "safe" for derivative cells to be implanted in patients ".
"Until a few years later, the fetal nerve cell transplant was used as a treatment for Parkinson's disease, and Lee and others began to study when the brains of rodents were implanted, whether the converted cancer cells will behave like normal neurons.
Samuel Lee and graduate student.
A method of happily developing and obtaining a patent for increasing the large output of cancer
Derived nerve cells in the laboratory
In the experiment of mice and mice, she and her husband John Q.
Trojanowski, both neuropathologists at the University of Pennsylvania medical school, found that when these cells were implanted into the animal's brain, they survived, mature and emit fibers of the same pathway as nearby nerve cells.
"We have a lot of animals and these neurons have a lot of different patches [implanted]
In different parts of the brain, "Li said.
"They survived and the fibers traveled long distances.
"But can this implant benefit patients?
No one imagined that such cells would be able to recover all connections lost during a stroke.
Some axon (
Nerve cell fiber)
The time of death after stroke exceeds 1 feet, extending from the brain to the lower part of the spinal cord.
"We have not tried to bridge this gap," Kondziolka said . ".
However, the researchers believe that these cells may in some way promote the recovery of survival neurons in damaged areas ---
Either by forming a shorter connection or by releasing a chemical growth factor.
To validate the idea, Lee and Trojanowski worked with researchers at the University of South Florida School of Medicine to study whether cell implantation contributed to the recovery of stroke in rats.
To their surprise, compared to rats who were not treated, rats who received nerve cell implantation after stroke had a significant improvement in memory and exercise.
Trojanowski recalled that their first thought when they saw the results was "we don't believe it!
We don't believe it!
"He speculated that the implanted cells strengthen nearby neurons by releasing chemical factors, thus promoting the healing of the damaged brain.
"They may talk to their neighbors like fitness coaches and cheer for them," he said . ".
Positive results from mice and monkeys, coupled with extensive safety studies in animals, convinced the Food and Drug Administration to approve a preliminary study of nerve cell implantation in stroke patients at the University of Pittsburgh.
On last June, when the first patient, Alma cherazini, underwent implant surgery, Lee and Trojanowski waited anxiously for her condition.
"When the patient came up and down from the table, our knees were shaking," Trojanowski said . ".
"We embraced it several times and said," Holy [expletive]
What did we do? ' . . .
We were very shocked and surprised by the core.
"Next: The Last larger study of more than a dozen patients in the Pittsburgh pilot study was undergoing nerve cell implantation surgery today.
In the coming weeks, Richard Mulvihill and other patients will have a special type of brain scan (
PET scan and functional MRI scan)
See if the implant makes any visible changes to how the damaged part of the brain works.
But scanning does not provide enough detail for doctors to see if the implanted cells survive and thrive.
However, this may be achieved one day if any implant patient finally receives an autopsy.
At the same time, in the coming months, when Kondziolka and his colleagues collected and analyzed the results of patients, they wanted to plan and seek approval for larger neural cell implantation trials, the trial will recruit more stroke patients.
It can test larger doses of cells and compare the effects of injecting these cells at different locations in the brain.
In the future, other researchers may test this implant to treat spinal cord injury and Huntington's disease, a degraded brain disease, Kondziolka said.
Moon Hill returned to his home in Florida to do daily exercises at the YMCA, hoping his memory and strength will improve this spring.
"I want it very much," he said, lying in the hospital room after two. hour surgery.
"I know they gave me something that could help me.
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