A Pioneer in the Use of Deep Brain Stimulation

“Our mission is to innovate, to constantly find new answers. And no one is doing that better today than the people at Penn Medicine.” - Gordon Baltuch, MD

Many people describe Gordon Baltuch, MD, Director of the Center for Functional and Restorative Neurosurgery, as a man of vision. This is not surprising, considering the fact that he’s been developing this skill since he was a boy.

“When I was a child, I was very close to my grandfather, who was a physician in a very different time and place,” Dr. Baltuch says, his eyes twinkling at the thought. “Sometimes he would go to patients’ houses. Sometimes patients would come to our house. On busy days, the living room became the waiting room. It was, at the end of the day, a very social experience.

“It was there that I first realized I could see myself going into medicine.”

Gordon Baltuch, MD

With this goal in mind, he pursued an undergraduate degree at Harvard, knowing all along what the next step in his path would be. In medical school, he gravitated at first towards neuroscience, then towards the more unknown world of neurosurgery, which just happened to be “a good fit.” The wisdom of his choice of medical specialization was confirmed by his early experience working at the Montreal Neurological Institute and Hospital in the late 1980s, where he was fortunate to be able to witness firsthand and later take part in some of the leading-edge work of the day at the intersection of neuroscience and medicine.

Then, once again, he had a vision of new and greater possibilities in his chosen field. So, in 1994, he packed his bags and headed for Europe, where Professor Alim Louis Benabid was pioneering deep brain stimulation (DBS) therapy for Parkinson's disease.

The cause of Parkinson’s disease, a degenerative disorder of the central nervous system, was at that time and is to this day unknown. The death of dopamine-generating cells in the substantia nigra part of the brain leads to the motor symptoms that traditionally characterize Parkinson’s, beginning with shaking, rigidity and other movement-related manifestations. Cognitive and behavioral problems, even dementia, are associated with advanced stages of the disease. The accumulation of rogue proteins called alpha-synucleins, combined with the lack of healthy dopamine generation and activity, causes the circuitry of the midbrain to function in abnormal electrical patterns and sometimes, in severe cases, to cease functioning at all.

Interested in reading more? 

Check out the full version of A Pioneer in the Use of Deep Brain Stimulation.

Relieve Your Stress With Mindfulness Meditation

Get a fresh start this spring by finding new balance in your work and home life with the Penn Program for Mindfulness.

The Penn Program for Mindfulness teaches how to use meditation as the primary tool for long-term stress management. Mindfulness meditation will help you manage the physical, psychological and behavioral symptoms of stress.

This highly acclaimed eight-week course will teach you a variety of meditation techniques to help cultivate relaxation, clarity and focus in your day-to-day life. You will learn to recognize your unique reactions to stress, find more effective ways to respond to stressful situations and discover how to use your own inner resources to attain greater health and well-being.

Program Details

The Penn Program for Mindfulness courses are offered in eight locations in PA and NJ. Courses will include a two-and-a-half-hour class each week, along with one full-day mindfulness retreat on Saturday, June 7. The registration deadline is April 24. Classes begin the week of April 28.

Learn more and register for the Penn Program for Mindfulness.

Center for Bloodless Medicine and Surgery Symposium

The Center for Bloodless Medicine and Surgery, a program for patients who prefer treatment or surgery without the use of blood or blood products such as red cells, white cells, platelets and plasma, will be holding a free symposium on Saturday, May 17.

This event will feature a presentation on the history of bloodless medicine from

Patricia Ford, MD

Patricia Ford, MD, Founder and Director of the Center for Bloodless Medicine and Surgery at Pennsylvania Hospital. It also will include panel discussions on what happens in the operating room, how the hospital identifies bloodless patients and when to enroll with the Center.

Event Details

Date: Saturday, May 17
Time: 1:00 p.m. to 3:00 p.m.
Location: Zubrow Auditorium
                Pennsylvania Hospital

                800 Spruce Street
                Philadelphia, PA 19107

To register, call 800-789-PENN (7366) or email BloodlessMedicine@uphs.upenn.edu.

About the Center for Bloodless Medicine

The Center for Bloodless Medicine and Surgery at Pennsylvania Hospital incorporates advanced technology and world-class medical specialists trained in patient blood management. Founded in 1996, this national and internationally-recognized program treats more than 600 patients per year and has options in nearly every medical specialty.

Bloodless Medicine Facts

• Bloodless medicine and surgery is a safe, proven and effective method of treating patients without the use of blood or blood products such as red cells, white cells, platelets and plasma.
• Patients who choose treatments without the use of blood often experience faster healing and recovery times and lower chance of infections.
• Bloodless medicine reduces reliance and associated costs on regional and national blood supplies.

Learn more about bloodless medicine and
the Center for Bloodless Medicine and Surgery

Roasted Sweet Potatoes & Brussels Sprouts with Herbs

In this beautiful dish of sweet potatoes and brussels sprouts, two herbs were teamed together to bring out a delightful experience your taste buds will love! Rosemary and fresh basil are always favorites for many of my dishes and I especially love it in this one. The natural sweetness of the potatoes blends nicely with the brussels sprouts.

Did you know sweet potatoes are very good for keeping your skin clear, smooth and young looking?  The orange color in the potatoes comes from beta-carotene, an antioxidant that converts to vitamin A in your body and switches on DNA that is responsible for producing new skin cells and getting rid of old ones.  That is an idea I love and we can all use smooth and clear skin. Brussels sprouts, believe it or not, have unique health benefits when it comes to your DNA as well.  A recent study showed improved stability of DNA inside our white blood cells after daily consumption of brussels sprouts. The repair and protection of our DNA plays a critical role in preventing cancer and slowing aging. Also, our bodies detox system needs ample amounts of sulfur to work effectively and brussels sprouts are rich in sulfur containing nutrients. Eating these two foods 3-4 times or more weekly helps to improve your immune function, provide you with an abundance of rich nutrients, protects your DNA and helps your body to detox more effectively.

I hope you love sweet potatoes and brussels sprouts as much as I do and will choose to add them to your diet, if you don't already.  There are a few different ways to make this dish.  You can steam the vegetables slightly and then mix with some olive oil, herbs, sea salt and pepper. Then bake for a short time at 350 degrees. The other method is to peel and chop the sweet potatoes, mix with brussels sprouts, olive oil, herbs, sea salt and pepper and bake for 1 hour at 350. Both methods work great.

Many diseases and health problems start with nutritional deficiencies. To avoid these deficiencies, fill up on foods rich in vitamins and minerals (like sweet potatoes & brussels sprouts) every day and limit or eliminate foods that have no benefit to your health.

Roasted Sweet Potatoes and Brussels Sprouts with Herbs
Printable Recipe
Serves 4

2 Sweet Potatoes (peeled and chopped)
1 pound fresh or frozen brussels sprouts
1/4 - 1/2  cup fresh basil (finely chopped)
1 teaspoon dried rosemary
1-2  tablespoons olive oil
sea salt and pepper to taste

Directions:
Peel sweet potatoes and chop into cubes.  Mix with brussels sprouts, basil, rosemary, olive oil, sea salt and pepper. Place in 350 degree oven for approximately 1 hour.  Do not overcook.  As soon as the sweet potatoes are tender, remove from oven.  ENJOY good health!!

Keto-adapted, but no ketones?

One of the cheapest and easiest ways to measure ketones is to use ketone test strips, e.g. Ketostix. Ketone test strips use a chemical reaction to measure acetoacetate (see below), usually in urine, though the same method can be used for blood. (Not to be confused with the blood strips used at home for beta-hydroxybutyrate.) However, acetoacetate test strips are of limited usefulness. For one thing, urine concentrations are affected by dilution, which means that they are affected by how much you drink.

But the problem is deeper than that. Acetoacetate is only one of the three ketone bodies (see below). Initially, when you start a ketogenic diet, acetoacetate will make up about half of the circulating ketones [1], but when you are keto-adapted, it makes up only about 20% of the ketone bodies in circulation (see below). Morover, the sensitivity of the strips is a little lower than optimal for our purposes. They register negative unless the concentration is quite high.

So, it is not uncommon for a keto-adapted person to measure negative for acetoacetate.

Different ketone bodies occur in different amounts

There are three compounds grouped together as ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. In keto-adapted people, acetoacetate levels are relatively low even though beta-hydroxybutyrate is high. Typically, beta-hydroxybutyrate levels are 4–5 times as high as acetoacetate. (Acetone makes up only about 2% of total ketone bodies [2].)

The graph above shows that in the ketosis of fasting, the proportion of acetoacetate (the top, white part of the bar) is much smaller than that of beta-hydroxybutyrate (the black part). In the study here, after 21 days of fasting, the average level of blood acetoacetate was 1.04 mmol/L, while the beta-hydroxybutyrate level was 4.95 mmol/L [3]. In another study of epileptic children on ketogenic diets, after 3 months, the average acetoacetate level was 1.182 mmol/L, while the average beta-hydroxybutyrate level was 4.21 [4].

The level of ketosis in fasting and in epileptic treatment is a little bit higher than for the typical ketogenic dieter who is simply trying to lose weight, enhance athletic performance, or improve their cardiovascular risk profile, for example. In those cases, beta-hydroxybutyrate levels are typically 1–3 mmol/L.

Since the ratio of acetoacetate to beta-hydroxybutyrate is only about 1:4, acetoacetate levels will be only about 0.25–0.75 mmol/L for keto-adapted people.The acetoacetate measure does not register as positive until about 0.5-1.0 mmol/L [5], so those values will often register as negative for acetoacetate.

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Here are some examples of negative acetoacetate, even while beta-hydroxybutyrate is very high.

There is a dangerous state that diabetics can get into called keto-acidosis, which is crucially different from nutritional ketosis (a safe and healthy state), but is often confused with it, because they both involve activation of ketogenesis. Ketone levels in keto-acidosis are much higher than in nutritional ketosis, and it is the monitoring of this state that ketone strips are optimised for. Even though ketone levels in keto-acidosis are higher than in nutritional ketosis, in one report it was found that 57% of diabetics with negative acetoacetate measurements were suffering from keto-acidosis [6].

Most of the cases of high beta-hydroxybutyrate in this study were not also positive for urine acetoacetate.

This flowchart shows that it is clinically accepted that even with very high beta-hydroxybutyrate levels, acetoacetate in urine and blood can be negative. The reason acetoacetate is bothered with at all is that it is relatively cheap and easy to measure.

What's the best way to measure ketosis?

Ketone test strips are a cheap and easy way to confirm ketosis when you have very high levels, such as during keto-adaptation. However, we would expect the false negative rate to be high for keto-adapted people, and for infants, (who are normally in consistent but mild ketosis while exclusively breastfed). So although it can be a good tool when you are starting a ketogenic diet, it is not necessarily reliable as you progress.

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A negative acetoacetate measure does not imply that you are not in ketosis.

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If you are troubleshooting, and need more accurate measurements, we strongly recommend a blood ketone meter for beta-hydroxybutyrate. However, be aware that the strips themselves are very expensive.

A new breath acetone meter is now on the market. It costs about $100, but it doesn't require any strips, so you pay only once. Unfortunately, like the acetoacetate strips, the measure is only semi-quantitative, and appears to have a relatively high minimum threshold for showing positive. We also don't know how well acetone correlates to beta-hydroxybutyrate, or to therapeutic results. Nonetheless, it is a promising technology, and it requires no pinpricks or pants down. We'd love to hear from you if you've given it a try.

References:

[1]

Evidence type: authority The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-Saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable Jeff Volek and Steven Phinney Publisher: Beyond Obesity LLC; 1St Edition edition (May 19, 2011) "Beta-hydroxybutyrate and acetoacetate are made in the liver in about equal proportions, and both are initially promptly oxidized by muscle. But over a matter of weeks, the muscles stop using these ketones for fuel. Instead, muscle cells take up acetoacetate, reduce it to beta-hydroxybutyrate, and return it back into the circulation. Thus after a few weeks, the predominant form in the circulation is beta-hydroxybutyrate, which also happens to be the ketone preferred by brain cells (as an aside, the strips that test for ketones in the urine detect the presence of acetoacetate, not beta-hydroxybutyrate). The result of this process of keto-adaptation is an elegantly choreographed shuttle of fuel from fat cells to liver to muscle to brain."

[2]

Evidence type: authority Henry's Clinical Diagnosis and Management by Laboratory Methods Richard A. McPherson, Matthew R. Pincus Elsevier Health Sciences, Sep 6, 201 "Whenever a defect in carbohydrate metabolism or absorption or an inadequate amount of carbohydrate is present in the diet, the body compensates by metabolizing increasing amounts of fatty acids. [...] In ketonuria, the three ketone bodies present in the urine are acetoacetic acid (20%), acetone (2%), and 3-hydroxybutyrate (about 78%)."

[3]	Evidence type: experiment Comparative measurements of glucose, beta-hydroxybutyrate, acetoacetate, and insulin in blood and cerebrospinal fluid during starvation. Owen OE, Reichard GA Jr, Boden G, Shuman C. Metabolism. 1974 Jan;23(1):7-14.

[4]

Evidence type: experiment A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Neal EG1, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. Epilepsia. 2009 May;50(5):1109-17. doi: 10.1111/j.1528-1167.2008.01870.x. Epub 2008 Nov 19. "One hundred forty-five children with intractable epilepsy were randomized to receive a classical or an MCT diet." [...] "Classical diets were started at a 2:1 ratio and gradually increased to a 4:1 ratio as tolerated over 1–2 weeks; in a few children the ratio was kept at 3:1 for longer because of tolerance problems. Protein was generally kept at World Health Organization (WHO) minimum requirements for age (World Health Organization, 1985). MCT diets were commenced on a full prescription for carbohydrate (generally 15% energy), protein (usually 10% energy), and long-chain fatty acids (usually 30% energy). The MCT fat was increased incrementally over a 7–10 day period as tolerated, to an initial level that was usually 40–45% of total dietary energy. Diets were fully supplemented with vitamins and minerals. "Subsequent to starting the diet, all children were reviewed as outpatients at 3, 6, and 12 months. They were also closely monitored by telephone between clinic visits. Diets were fine-tuned as necessary to improve ketosis and optimize seizure control. The parameters within which the two diets could be modified were defined before study commencement. Overall energy prescription was adjusted on both diets as needed. Ketogenic ratio on the classical diets was kept between 2:1 and 5:1 (most classical diet children were on a 4:1 ratio, a few were on a 3:1 ratio, and two children needed a 2:1 ratio for a short period). Fine-tuning on the MCT diets involved adjusting the proportion of MCT and carbohydrate in the prescription. MCT was usually started at 40–45% of energy, and was increased up to 60% if necessary and tolerated. Carbohydrate was usually started at 15% of energy, and was reduced to a lowest value of 12% if necessary. Carbohydrate was reduced to improve ketosis only if an increase in MCT was not possible because of poor tolerance. Other modifications on both diets were fluid intake and meal distribution. Protein intake was increased as needed to meet requirements."

[5]

Evidence type: authority Ketostrips use nitroprusside to detect acetoacetate levels. We have seen claims that they can detect as little as 5 mg/dl (0.5 mmol/L), only 10 mg/dl, or, most commonly, the minimum is given as the range 5–10 mg/dl. Here is an example of each: From: Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Walker HK, Hall WD, Hurst JW, editors. Boston: Butterworths; 1990. "Nitroprusside is available as a test tablet (Acetest) and as a coated reagent strip (Ketostix), both manufactured by the Ames Division of Miles Laboratories, Inc., Elkhart, Indiana. With Acetest, after 30 seconds the color development is compared to a chart and judged negative, small, moderate or large. The tablet will detect 5 to 10 mg/dl of acetoacetate and 20 mg/dl of acetone. The quantitative range included in each category is 5 to 20 mg/dl for small, 20 to 40 mg/dl for moderate, and 40 mg/dl or greater for large. With Ketostix, the strip is momentarily dipped into the urine specimen or passed through in the urinary stream and compared to a color chart 1 minute later. The scale is negative, trace, small, moderate, and large. The strip is capable of detecting 5 mg/dl acetoacetate but is not reactive to acetone. The ranges are wider and shifted somewhat to the right in the higher zones compared to Acetest so that only 16% of samples containing 20 mg/dl acetoacetate are read as moderate while 24% of samples containing 80 mg/dl acetoacetate are still called moderate. Only 15% of the samples containing 40 mg/dl acetoacetate are judged to be large; 76% are large at 80 mg/dl and 100% at 160 mg/dl. The Ketostix test is most accurate when urines are tested with a high specific gravity (between 1.010 and 1.020) and low-pH. Highly pigmented urine specimens may yield false positive readings. Levodopa will also cause a false positive result. Ketostix strips are less sensitive than Acetest tablets and have a high degree of variability between lots. Acetest, with sensitivity in the 5 mg/dl range, is the preferable method." From: Medical Laboratory Science : Theory And Practice Ochei Et Al. Tata McGraw-Hill Education, Aug 1, 2000. p 134 "Ketostix (Ames) This test strip will detect 0.5–1.0 mmol/L (5–10 mg/dl) of acetoacetic acid" From: Blackwell's Five-Minute Veterinary Consult: Laboratory Tests and Diagnostic Procedures Shelly L. Vaden, Joyce S. Knoll, Francis W. K. Smith, Jr., Larry P. Tilley John Wiley & Sons, Jun 13, 2011 "Only acetoacetate and acetone are detectable by reagent strips or tablet tests, which are based on the reaction of acetoacetate (more reactive) and acetone (less reactive) with nitroprusside. "Urine (and blood) can be screened for ketones by using either reagent strips or tablets [...] The [tablet] is more sensitive than reagent strips and will detect 5 mg/dL of ketones compared with 10 mg/dL for dipsticks."

[6]

Evidence type: authority, since we can't access the full text From: Development of Paper-strip Test for 3-Hydroxybutyrate and its Clinical Application Yutaka Harano, M.D., Masaaki Suzuki, M.D., Hideto Kojima, M.D., Atsunori Kashiwagi, M.D. Ph.D., Hideki Hidaka, M.D. Ph.D. and Yukio Shigeta, M.D. Ph.D. Diabetes Care September/October 1984 vol. 7 no. 5 481-485 "MacGillivray et al. recently reported that 57% of the urine tests that were negative for ketone bodies by acetest were associated with elevated plasma 3-OHBA in insulin-dependent diabetes. [...] "MacGillivray, M. H., Voorhess, M. L., Putnam, T. I., Li, P. K., Schaefer, P. A., and Bruck, E.: Hormone and metabolic profiles in children and adolescents with Type I diabetes mellitus. Diabetes Care 1982; 5(Suppl .l):38-47"

What to Expect at Your Annual Physical, Part 2: Vaccinations

Lori M. Noble, MD, a primary care physician at Spruce Internal Medicine, located at the new Penn Medicine Washington Square building, discusses what to expect at your annual physical. This is a two-part series. Interested in part 1? Check it out now.

Lori M. Noble, MD

As adults, many of us cannot recall the last time we had to get a routine series of vaccines. Maybe we just have a vague recollection of needing shots before college or before accepting a new job.

That being said, vaccines are an extremely important part of routine care well into adulthood. Some vaccines continue to be recommended for all age groups, while others are offered only at certain age milestones or in those with certain health conditions.

It is important to know what vaccines you may be eligible for, and remember, it’s just a sting or a pinch today that can help prevent disease tomorrow.

HPV vaccination (aka Gardasil)

WHO: Males and females from age 9-26.
WHY: To protect you from four strains of the Human Papilloma Virus, two of which cause genital warts in men and women, and two of which can lead to cervical cancer in women.
NOTES: 1) The HPV vaccine is a series of three shots. The second is given two months after the first and the third is given four months after the second. 2) Not all insurance companies are consistently covering the vaccine for young men, so check with your insurance company before visiting your doctor.

TDaP vaccination (aka Adacel, Boostrix, Daptacel)

WHO: All adults age 19 and older should receive a single dose of Tdap to replace a single dose of the “every 10 year” Td booster.
WHY: To boost protection against Pertussis (which is the infection that causes whooping cough in children), in addition to boosting protection against Tetanus and Diphtheria. There has been an increase in whooping cough in children because as adults, our protection (i.e immunity) against the infection goes down. We can then transmit it to children who are not fully vaccinated.
NOTES: All pregnant women should receive the vaccine with each pregnancy, regardless of prior vaccination.

Flu vaccination

WHO: All adults once per year (typically August-February).
WHY: To protect against the influenza virus and complications, such as pneumonia.
NOTES: There are multiple kinds of flu vaccines, and your doctor will recommend the best one for you based on your age and any other medical conditions you may have.

Pneumonia vaccination (aka Pneumovax)

WHO: One time in all adults age 65 and older AND in all adults under age 65 with any of the following: diabetes, COPD (i.e. emphysema), HIV, heart failure, asthma, chronic hepatitis, cancer or current smokers. WHY: To protect against potentially deadly pneumonia infection and its complications.
NOTES: 1) If the vaccine is given before the age of 65 for any of the above conditions, a second dose should be given as a booster at age 65. 2) In those adults whose immune systems are poor (i.e. cancer patients on chemotherapy), a booster should be given every five years, regardless of age.

Shingles vaccination (aka Zostavax)

WHO: One time in all adults, age 60 and older, who have ever had chickenpox (or whose chickenpox history is unknown).
WHY: To protect from the reactivation of the chicken pox virus, which can cause a painful, blistering rash, called shingles. The rash can leave behind permanent nerve damage at the site of the rash, leading to chronic pain.
NOTES: 1) Adults whose immune systems are very poor should not get the vaccine. 2) The CDC (Centers for Disease Control) currently recommends vaccinating all adults over the age of 50, but insurance companies are currently not approving the vaccine for those between the ages of 50-59. 3) If you have Medicare, you may need to get this shot administered at your local pharmacy, NOT in the doctor’s office, in order to be covered by insurance. Ask your doctor or your pharmacist if this applies to you.

The relationship you build with your primary care doctor is one of the most important you’ll ever have. Primary care providers are there to listen to your special concerns and help you make informed decisions about maintaining your health. If you have additional questions, please speak with your physician.

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