Wednesday, December 18, 2013

Best Post of September 2013

The next in our "Best of the Month" series is from September 16, 2013

Two UC Davis Neurosurgeons Resign After Intentionally Infecting Intracranial Glioblastomas with Bowel Bacteria

The Sacramento Bee recently reported that two UC Davis neurosurgeons who intentionally infected three glioblastoma patients with bowel bacteria have resigned their posts after the university found they had "deliberately circumvented" internal policies, "defied directives" from top leaders and sidestepped federal regulations, according to newly released university documents.

Neurosurgeon J. Paul Muizelaar, MD

Dr. J. Paul Muizelaar, 66, the former head of the neurosurgery department, and his colleague, Dr. Rudolph J. Schrot, violated the university's faculty code of conduct. All three patients consented to the procedures in 2010 and 2011. Two of the patients died within weeks of their surgeries, while the other survived more than a year after being infected.

Read more here:

Muizelaar and Schrot called their novel approach "probiotic intracranial therapy," or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients' brains or bone flaps. The doctors theorized that an infection might stimulate the patients' immune systems and prolong their lives. The first patient lived about 5 1/2 weeks. The second survived another year, an outcome that buoyed the doctors and seemed to bolster their theory, they said. The institutional trouble began in March 2011, when a newly diagnosed third patient developed sepsis, became unresponsive and died two weeks after being deliberately infected. The university's first internal investigation soon followed.

Muizelaar and Schrot did not complete a study on rats before they began treating the three human patients, despite an FDA directive in 2008 that "animal studies will be necessary prior to entering into the clinic with your proposed therapy," according to an email to Schrot from an FDA official. When asked by a compliance investigator why animal trials were not done first, Schrot allegedly responded that such testing would take "10 years … his entire career," one internal review states. The investigator found Schrot's "eagerness to proceed" to be concerning and his actions "reckless."

Muizelaar, one of the highest paid employees in the University of California system, stepped down effective June 27. He earned more than $907,000 last year, the 33rd-highest gross pay in the UC system.  Schrot, 45, an associate professor who made about $512,000 last year, will leave his post at the end of August. Both doctors have sharply criticized the findings, characterizing the internal investigations as biased and incomplete. The surgeons maintain they were acting in the best interests of their desperately ill patients, whose prognoses for survival were poor. Both doctors opted not to appeal the university's findings because they determined it would be fruitless."I lost confidence, if you will, in the ability of the university administration to fairly handle it," Schrot said Friday in the office of his Sacramento attorney.

Read more here:
One colleague, Dr. David Asmuth, an infectious disease specialist who co-chaired an oversight committee for university research, called the surgeons' procedure "the worst case of human subjects research he had ever seen."

Read more here:

"I was simply thinking that I could help patients," Muizelaar said. "My whole medical practice is guided by actually only one principle, namely: What would I do for my mother, my son, myself?"

Tuesday, December 10, 2013

The Solution to the Football Concussion Dilemma: Hold All Games at High Altitude

A new study shows that high school athletes playing at higher altitudes suffer fewer concussions than those closer to sea-level, a phenomenon attributed to physiological changes in the brain causing it to fit more tightly in the skull.

"This is the first time any research has linked altitude to sports-related concussion," said Dawn Comstock, PhD, associate professor of epidemiology at the Colorado School of Public Health and co-author of the study. "It appears that when you are at altitude there may be a little less free space in the skull so the brain can't move around as much."

The study, first-authored by David Smith, MD, of Cincinnati Children's Hospital Medical Center, was published recently in the Orthopaedic Journal of Sports Medicine.

The researchers analyzed concussion statistics from athletes playing multiple sports in 497 high schools from across the U.S. with altitudes ranging from 7 feet to 6,903 feet with 600 feet being the median. They also examined football separately since it has the highest concussion rate of high school sports. The numbers came from the National High School Sports-Related Injury Surveillance System directed by Comstock.
The results showed a 31 percent decrease in concussion rates among all high school sports played at altitudes of 600 feet and above. Concussion rates for high school football players at these altitudes decreased by 30 percent.

"Vasogenic edema in the brain leads to increased extravascular water," the study says. "These two adaptations would also lead to a tighter packaging of the brain with increased blood cell content surrounding the brain."
"If this study is correct, we should look to replicate our findings in the National Football League," Comstock said. "For example, if the Broncos play the Chargers in San Diego or the Dolphins in Miami they should experience more concussions than when they play here in Denver."

The incidence of concussion among high school athletes has grown tremendously. The Centers for Disease Control and Prevention estimate the annual incidence of sports-related traumatic brain injury in the U.S. at 1.6 million to 3.8 million with many more going undiagnosed. In a recent 10-year period there has been a 100 percent increase among 8 to 13-year-olds and a 200 percent increase among 14 to 19-year-olds in sports-related emergency room visits for concussion.

Interestingly, scientists found that putting mild pressure on a rat's jugular vein increased pressure on the brain and reduced injury from concussion by 83 percent.

Thanks to the esteemed Dr. Doug Shevlin, pictured below, for alerting me to this remarkable finding.

Douglas Shevlin, MD

Tuesday, December 3, 2013

What happened to neuropathology in 1946?

The esteemed Dr. Jim Mandell and his son were recently playing with the amazing Google Books Ngram Viewer. Google Ngram searches a huge corpus of books for the mention of a particular search term. It then graphs the frequency with which that term appears over time. On a whim, the Mandell's entered the search term "neuropathologist". Here's the resulting graph:

I couldn't fit the y-axis label in the picture, but it ranges from 0% up to 0.00000300%. Dr. Mandell challenges his neuropathology colleagues to explain the sharp spike in the usage of "neuropathologist" around 1946-47. Please enter your speculations in the comment section. Dr. Mandell also points out the lamentable fact that it "appears we are past our peak".

Neuropathology Blog is Signing Off

Neuropathology Blog has run its course. It's been a fantastic experience authoring this blog over many years. The blog has been a source...