Category Archives: Medical Research

New Scientific Study Finds Evidence of Hyperbaric Oxygen Therapy Efficacy for Patients with Mild Traumatic Brain Injury

March 26, 2022

HBOT at 1.5 ATA oxygen Promotes Symptomatic and Cognitive Improvements for Patients with mild Traumatic Brain Injury/Persistent Postconcussion Syndrome in a Narrow Range of Pressure

New Orleans, LA — March 26, 2022: Today, IPAK announced the publication of a systematic review (latest study) on hyperbaric oxygen therapy (HBOT) efficacy in mild traumatic brain injury Persistent Postconcussion Syndrome (PPCS).

Following multiple randomized and randomized controlled studies, the review found HBOT at 1.5 ATA oxygen to provide improvements in symptoms and cognition for patients with mild traumatic brain injury. These improvements — ranging from solely symptomatic to both cognitive and symptomatic — are significant enough to satisfy recommendations set in place for HBOT treatments by the Center for Evidence-Based Medicine and American Society of Plastic Surgeons.  The systematic review concludes that HBOT meets the highest level of scientific evidence and merits a Grade A Practice Recommendation, that HBOT should be delivered to patients with persistent postconcussion syndrome unless a “clear and compelling rationale for an alternative approach is present.”

Dr. Paul Harch, principal investigator for the study, says the contribution is reassuring to those questioning the efficacy of HBOT. “This scientific review brings clarity at last to the confusion and controversy surrounding traumatic brain injury and hyperbaric oxygen therapy,” he said. “The Level 1 Evidence and Grade A Practice Recommendation will allow this life and quality-of-life-saving therapy to give people back their lives.”

Patients undergo hyperbaric oxygen therapy by breathing increased oxygen while under increased pressure. This allows the lungs to dissolve increased amounts of oxygen in blood that is delivered by the circulation to all areas of the body, especially those wounded tissues with less oxygen.  In conjunction with the increased amount of pressure the oxygen and pressure stimulate the body’s natural healing process to repair the wounds in traumatic brain injury.

Harch’s study reviewed how the intensity of oxygen dosage and pressure impacted treatment, finding that both positive and negative results occurred with high and low doses.  Surprisingly, the most influential effects occurred with increased pressure within a narrow range.  The elucidation of the independent and combined effects of oxygen and pressure for the first time in the 360-year history of hyperbaric medicine represents a key advance to the field of hyperbaric medicine, medicine, and neurorehabilitation.

More importantly, this is uplifting news for patients with PPCS, who can experience concussion-like symptoms even when at rest, as well as following physical and/or cognitive exertion. Over time, this may significantly impact their sleep, behavioral, cognitive, and physical performance.

PPCS is experienced by 10-15% of individuals who’ve experienced a concussion, including high school athletes, and as many as 44% of those with loss of consciousness.  Currently, there is no standard of care for the treatment of individuals with PPCS.  This systematic review now shows that there is more than hope, there is treatment.

About Paul G. Harch, M.D.: Paul G. Harch is a hyperbaric medicine clinician and Clinical Professor of Medicine at the Section of Emergency Medicine, LSU School of Medicine, New Orleans. Two of the studies in the systematic review were published by Dr. Harch under LSU’s IRB approval.  Dr. Harch’s research with hyperbaric oxygen treatment has encompassed a wide range of neurological conditions, including decompression sickness, Alzheimer’s Disease, traumatic brain injury and childhood drowning.

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CONTACT INFORMATION:

Paul G. Harch, M.D. (LSU) or James Lyons-Weiler, PhD

Contact: info@ipaknowledge.org

    

Combination of Two Over-the-Counter Drugs Reduces COVID-19 Inpatient Death Rate

Birmingham, Ala. – Treating severe and critical hospitalized COVID-19 patients using two common over-the-counter (OTC) drugs reduced the inpatient death rates down to 15.5%, compared to published inpatient fatality rates of 21 to 25.7% in New York City, Louisiana, and the United Kingdom.  Thus, in essence the dual-drug treatment resulted in a one third reduction in the rate of death in hospitalized patients.  They also reduced the intubation rate down to only 16.4% in these high acuity inpatients. The clinical research findings were published in August 2020 in the journal – Pulmonary Pharmacology & Therapeutics.

The drug combination included an antihistamine and an antacid, commonly found on shelves and safely used for decades.  These two medications, cetirizine (e.g., Zyrtec(TM)) and famotidine (Pepcid(TM)), work to block H1 and H2 histamine receptors, producing a one-two punch against inflammation and presumably blocking the cytokine storm, according to Reed Hogan, II MD, of GI Associates in Jackson, Mississippi.  Hogan initiated this collaboration with pulmonologists from Jackson Pulmonary Associates, who were treating COVID-19 inpatients.  “I wanted to see if we blunt the cytokine storm with medications anyone in the world can find and afford,” said Hogan.

The physician-sponsored cohort study analyzed a group of 110 severe and critical inpatients with an average age of 63.7. Based in Mississippi, where general health is often compromised due to socio-economic issues, these very ill patients averaged a high 2.7 in co-morbidities, most notably hypertension, obesity, and diabetes. Of those patients, 59 percent were African-American and 59 percent female.

While many of the other current medical treatments for COVID-19 require expensive drugs or biologics, this protocol uses affordable drugs already on pharmacy shelves. The savings potential could reduce treatment to less than $50 in drug costs, a boon for people without health insurance.

While other research since the initial study shows that famotidine alone may not effective in hospitalized patients, the original study provides evidence of the treatment effectiveness of famotidine in combination with cetirizine in hospitalized patients.

It also appears that H1 histamine receptor antagonists alone are effective in elderly patients, but not in hospitalized elderly patients.

“The two OTC drugs are historically safe, inexpensive, and are readily accessible within both affluent and impoverished countries across the globe.  Blocking histamine to reduce inflammation in COVID-19 patients is logical,” said Thomas P. Dooley, Ph.D. a Birmingham, Ala.-based drug developer, collaborator, and coauthor on the study. The two histamine-blocking drugs are already approved for other medical indications by the Food and Drug Administration (FDA), therefore physicians may choose to use this new approach off-label. 

Testing on a larger scale in controlled randomized trials is warranted by these initial favorable results, according to Hogan.

SOURCE: Tom Dooley

Individualized brain cell grafts reverse Parkinson’s symptoms in monkeys

Grafting neurons grown from monkeys’ own cells into their brains relieved the debilitating movement and depression symptoms associated with Parkinson’s disease, researchers at the University of Wisconsin–Madison reported today.

In a study published in the journal Nature Medicine, the UW team describes its success with neurons made from induced pluripotent stem cells from the monkeys’ own bodies. This approach avoided complications with the primates’ immune systems and takes an important step toward a treatment for millions of human Parkinson’s patients.

“This result in primates is extremely powerful, particularly for translating our discoveries to the clinic,” says UW–Madison neuroscientist Su-Chun Zhang, whose Waisman Center lab grew the brain cells.

Parkinson’s disease damages neurons in the brain that produce dopamine, a brain chemical that transmits signals between nerve cells. The disrupted signals make it progressively harder to coordinate muscles for even simple movements and cause rigidity, slowness and tremors that are the disease’s hallmark symptoms. Patients — especially those in earlier stages of Parkinson’s — are typically treated with drugs like L-DOPA to increase dopamine production.

Standing at center, Su-Chun Zhang, professor of neuroscience in the School of Medicine and Public Health, talks with postdoctoral student Lin Yao as she prepares stem-cell cultures in the Zhang’s research lab at the Waismam Center at the University of Wisconsin-Madison on March 8, 2013. (Photo by Jeff Miller/UW-Madison)

Su-Chun Zhang

Marina Emborg

“Those drugs work well for many patients, but the effect doesn’t last,” says Marina Emborg, a Parkinson’s researcher at UW–Madison’s Wisconsin National Primate Research Center. “Eventually, as the disease progresses and their motor symptoms get worse, they are back to not having enough dopamine, and side effects of the drugs appear.”

Scientists have tried with some success to treat later-stage Parkinson’s in patients by implanting cells from fetal tissue, but research and outcomes were limited by the availability of useful cells and interference from patients’ immune systems. Zhang’s lab has spent years learning how to dial donor cells from a patient back into a stem cell state, in which they have the power to grow into nearly any kind of cell in the body, and then redirect that development to create neurons.

“The idea is very simple,” Zhang says. “When you have stem cells, you can generate the right type of target cells in a consistent manner. And when they come from the individual you want to graft them into, the body recognizes and welcomes them as their own.”

The application was less simple. More than a decade in the works, the new study began in earnest with a dozen rhesus monkeys several years ago. A neurotoxin was administered — a common practice for inducing Parkinson’s-like damage for research — and Emborg’s lab evaluated the monkeys monthly to assess the progression of symptoms.

“We evaluated through observation and clinical tests how the animals walk, how they grab pieces of food, how they interact with people — and also with PET imaging we measured dopamine production,” Emborg says. (PET is positron emission tomography, a type of medical imaging.) “We wanted symptoms that resemble a mature stage of the disease.”

The neuron-grafting approach in monkeys takes an important step toward a treatment for millions of human Parkinson’s patients.

Guided by real-time MRI that can be used during procedures and was developed at UW–Madison by biomedical engineer Walter Block during the course of the Parkinson’s study, the researchers injected millions of dopamine-producing neurons and supporting cells into each monkey’s brain in an area called the striatum, which is depleted of dopamine as a consequence of the ravaging effects of Parkinson’s in neurons.

Half the monkeys received a graft made from their own induced pluripotent stem cells (called an autologous transplant). Half received cells from other monkeys (an allogenic transplant). And that made all the difference.

Within six months, the monkeys that got grafts of their own cells were making significant improvements. Within a year, their dopamine levels had doubled and tripled.

“The autologous animals started to move more,” Emborg says. “Where before they needed to grab the cage to stand up, they started moving much more fluidly and grabbing food much faster and easier.”

The monkeys who received allogenic cells showed no such lasting boost in dopamine or improvement in muscle strength or control, and the physical differences in the brains were stark. The axons — the extensions of nerve cells that reach out to carry electrical impulses to other cells — of the autologous grafts were long and intermingled with the surrounding tissue.

“They could grow freely and extend far out within the striatum,” says Yunlong Tao, a scientist in Zhang’s lab and first author of the study. “In the allogenic monkeys, where the grafts are treated as foreign cells by the immune system, they are attacked to stop the spread of the axons.”

The results are promising enough that Zhang hopes to begin work on applications for human patients soon.

The missing connections leave the allogenic graft walled off from the rest of the brain, denying them opportunities to renew contacts with systems beyond muscle management.

“Although Parkinson’s is typically classified as a movement disorder, anxiety and depression are typical, too,” Emborg says. “In the autologous animals, we saw extension of axons from the graft into areas that have to do with what’s called the emotional brain.”

Symptoms that resemble depression and anxiety — pacing, disinterest in others and even in favorite treats — abated after the autologous grafts grew in. The allogenic monkeys’ symptoms remained unchanged or worsened.

The results are promising enough that Zhang hopes to begin work on applications for human patients soon. In particular, Zhang says, the work Tao did in the new study to help measure the relationship between symptom improvement, graft size and resulting dopamine production gives the researchers a predictive tool for developing effective human grafts.

SOURCE: news.wisc.edu

Accelerating and Improving Research on Brain Injuries via Data Sharing

The web-computing platform was created by IU scientists to support and publish reproducible neuroscience research

Scientists in the United States, Europe and South America are reporting how a new cloud-computing web platform allows scientists to track data and analyses on the brain, potentially reducing delays in discovery.

The project, called brainlife.io, is led by Franco Pestilli, associate professor in the Indiana University Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences and a member of the IU Network Science Institute, in collaboration with colleagues across the university. At IU, it is speeding research on disorders such as dementia, sports concussion and eye disease.

Brainlife logo
The logo of brainlife.io, a cloud-computing web platform that allows scientists to track data and analyses on the brain.

A new paper on the project was published May 30 in the journal Scientific Data.

“Scientists are increasingly embracing modern technology to reduce human errors in scientific research practice,” said Pestilli, who established brainlife.io in 2017 with support from the National Science Foundation and Microsoft.

“This article describes a unique mechanism by which scientists across the world can share data and analyses, which allows them to reproduce research results and extend them to new frontiers of human understanding,” he added. “The benefit of such a platform is faster research on brain disease.”

The system manages all aspects of research where people are more likely than machines to make mistakes, such as keeping track of data and code for analyses, storing information, and producing visualizations.

At IU, brainlife.io is being used to advance research on multiple health care research studies. Examples include:

The new paper provides a “case study” on how to generate a full research study, including data collection, analysis and visualization, on the brainlife.io platform. It also describes how the system preserves data and analyses in a single digital record to create reusable research assets for other scientists to use in their work.

“I like to refer to the new technology as a process of ‘data upcycling,'” Pestilli said. “The new records that scientists create and share on brainlife.io can be easily reused by others to go beyond the goals of the original study.”

For example, a study on traumatic brain injury could potentially combine data from a study on Alzheimer’s disease to understand underlying biological mechanisms in both conditions.

Importantly, Pestilli added, brainlife.io is designed to store and process data derived from diffusion-weighted magnetic resonance imaging — a form of imaging that uses water molecules in the brain to create a highly detailed roadmap of the nerve tracks in the brain — as well as tractography, a 3D modeling technical to visually represent these nerves and understand the network of connections that make up the brain.

Franco Pestilli
Franco Pestilli. Photo by Eric Rudd, Indiana University

“The use these imaging techniques has revolutionized knowledge about networks inside the brain and the impact of the brain’s white matter on human behavior and disease,” Pestilli said. It also generates enormous amounts of data that require serious computer resources to store and analyze.

Some of this computing power comes from Microsoft, which chose brainlife.io as one of the first eight projects to benefit from the company’s initiative to award $3 million in compute credits to projects under the NSF’s Big Data Spokes and Planning projects, of which IU is a part. The project is also supported under the NSF’s BRAIN Initiative, a federal project to generate new physical and conceptual tools to understand the brain.

IU contributors to brainlife.io include Soichi Hayashi, a software engineer at the IU Pervasive Technology Institute; graduate students Brad Caron, Lindsey Kitchell, Brent McPherson and Dan Bullock; and undergraduate students Yiming Qian and Andrew Patterson. Bullock and McPherson were supported by grants from the National Institutes of Health and NSF. Additional authors on the article include researchers at Indiana University, the University of Michigan at Ann Arbor, Northwestern University, the University of Trento in Italy and CONICET in Argentina.

SOURCE: NEWS.IA.EDU Credit: Kevin Fryling