Experimental Drug Stops Parkinson’s Disease Progression in Mice

Researchers at Johns Hopkins University School of Medicine published an article in Nature Medicine Journal outlining how administration of a drug called NLY01 stopped the progression of Parkinson’s disease in mice specially bred to develop this illness for research purposes. The medication is an alternative form of several diabetic drugs currently on the market including Byetta, Victoza and Trulicity. Those drugs penetrate the blood brain barrier poorly. NLY01 is designed to penetrate the blood brain barrier.

In one study, researchers injected the mice with a protein known to cause severe Parkinsonian motor symptoms. A second group received the protein plus NLY01. That group did not develop any motor symptoms of Parkinson’s disease. The other group developed profound motor impairment.

In a second experiment, they took genetically engineered mice who normally succumb to the disease in slightly more than a year of life. Those mice, when exposed to NLY01, lived an extra four months.

This is positive news in the battle to treat and prevent disabling symptoms in the disease that affects over 1 million Americans. Human trials will need to be established with questions involving whether the drug is even safe in humans? If safety is proven then finding the right dosage where the benefits outweigh the risks is another hurdle. The fact that similar products are currently being used safely to treat Type II Diabetes is noteworthy and hopefully allows the investigation to occur at a faster pace.

Parkinson’s disease is a progressive debilitating neurologic disorder which usually starts in patient’s 60 years of age or greater. Patients develop tremors, disorders sleeping, constipation and trouble moving and walking. Over time the symptoms exacerbate with loss of the ability to walk and speak and often is accompanied by dementia.

Advertisements

More Good News for Coffee Drinkers

When I first started practicing, fresh out of my internal medicine residency and board certification, we were taught that consuming more than five cups of coffee per day increased your chances of developing pancreatic cancer. Thankfully that theory has been proven to be false.

Last week I reviewed a publication in a peer reviewed journal which showed that if you infused the equivalent of four cups of coffee into the energy producing heart cell mitochondria of older rodents, those mitochondria behaved like the mitochondria found in very young healthy rats. The authors of that article made the great leap of faith by suggesting that four cups of caffeinated coffee per day was heart healthy.

This week’s Journal of the American Medical Association Internal Medicine published a study which said if you drank eight cups of coffee per day your mortality from all causes diminished inversely. Their study included individuals who were found to be fast and slow metabolizers of caffeine. It additionally made no distinction between ground coffee, instant coffee or decaffeinated coffee.

The research study investigated 498,134 adults who participated in the UK Biobank study. The mean age of the group was 57 years with 54% women and 78% coffee drinkers. The study participants filled out questionnaires detailing how much coffee they drank and what kind. During a 10 year follow-up there were 14,225 deaths with 58% due to cancer and 20% due to cardiovascular disease. As coffee consumption increased, the risk of death from all causes decreased. While instant coffee and decaffeinated coffee showed this trend, ground coffee showed the strongest trend of lowering the mortality risk.

This is an observational study and, by design, observational studies do not prove cause and effect. It is comforting to know however that having an extra cup or two seems to be protective rather than harmful. At some point a blinded study with true controls will need to be done to prove their point. If the caffeine doesn’t keep you up or make you too jittery, and the coffee itself dehydrate you or give you frequent stools, then drink away if you enjoy coffee in large volume.

Fish, Fish Oils and Cardiovascular Disease

Years ago the scientific researcher responsible for the promotion of fish oils as an antioxidant and protector against vascular disease recommended we all eat two fleshy fish meals of cold water fish a week. He continued to endorse this dietary addition and included canned tuna fish and canned salmon in the types of fish that produced this positive effect.

Over the years I heard him lecture at a large annual medical conference held in Broward County and he fretted about the growth of the supplement industry encouraging taking fish oils rather than eating fish. He worried about the warnings against eating all fish to women of child bearing age because of the fear of heavy metal contamination and knew that the fish oils and omega 3 Fatty Acids played a developmental role in a growing fetus and child.

I then attended lectures, in particular one sponsored by the Cleveland Clinic, during which they promoted Krill oil as the chosen form of fish oil supplements because it remained liquid and viscous at body temperature of 98.6 while others solidified. I listened to this debate only to hear the father of the science speak again and this time advocate that one or two fleshy fish meals a month was adequate to obtain the protective effect of Omega 3 Fatty acids. He felt that the supplements did not actually provide a protective effect as eating real fish did. Since I love to eat fresh fish I had no problem with this message but others are not comfortable buying and preparing fish at home or eating it at a restaurant. Supplements to them were the answer.

Steve Kopecky, M.D. examined the question in an article published in JAMA Cardiology this week. He looked at 77,917 high risk individuals already diagnosed with coronary artery disease and vascular disease who were taking supplements to prevent a second event. His study concluded that taking these omega 3 supplements had no effect on the prevention of recurrent cardiovascular events. The study did not discuss primary prevention for those who have not yet had a vascular illness or event.

Once again it seems that eating fish in moderation, like most anything, is the best choice. I will continue to eat my fresh fish meals one or two times per week, not necessarily for the health benefit but because I enjoy eating fresh fish.

I advise those worried about preventing primary or secondary heart and vascular disease to find a form of fish they can enjoy if they want this benefit. If you really wish to reduce your risk of a cardiovascular event; I suggest you stop smoking, control your blood pressure and lipid profile, stay active and eat those fresh fish meals.

Primary Care Docs Outperform Hospitalists …

A study published recently in JAMA Internal Medicine looked at 650,651 Medicare patients hospitalized in 2013. It showed that when patients were cared for by their own outpatient physician they had a slightly better outcome than when the patients were attended to by full-time hospital based specialists who had not previously known them.

As an internal medicine physician who maintains hospital privileges, as well as caring for patients in an office setting, this study supports the type of medicine I have been trying to practice for the last 38 years. However, I am not naïve enough to believe it entirely.

In recent months similar studies have touted the benefit of female physicians over their male counterparts, younger physicians over older physicians and even foreign trained physicians over those trained in the USA. Based on these studies, one might conclude you should be treated by a young female outpatient physician who trained in a foreign country. While the JAMA study shows the success of the outpatient primary care physician, those in hospitalist medicine could similarly produce their own studies showing the benefit of using a hospital based physician or hospitalist.

I do believe having a familiar physician, you know and trust, adds a major level of comfort when you are ill. Having that physician consult within his or her referral network of physicians who know how that doctor expects the communication between doctors, and care to occur, is an additional benefit.

The fact that your personal physician knows what you look like in health gives them a distinct advantage in recognizing when you are ill. They know you and all about you and that helps. It especially helps patients with complex medical issues who require more time and thought. Being able to review the old records and previous specialty consultations which you were a part of seems to impart an advantage that someone just joining the care team does not yet possess.

This study does not say that outpatient primary care docs are better than hospitalists. It only points out that in a senior citizen population in 2013, patients cared for by their own primary care doctor had a better 30 day survival after a hospital stay.

Inflammation as a Cause of Heart Attacks and Strokes

Years ago I attended a series of lectures sponsored by the Cleveland Clinic to promote its proprietary lab tests that were geared to detect previously undetectable causes of heart attacks and strokes. A cardiologist at Cleveland Clinic, along with a research nurse out of Emory University Hospital and Medical Center, noted that 50% of the men having heart attacks and strokes were within the recommended life and health guidelines. They didn’t smoke, their blood pressures were controlled, they had lipids within the recommended guidelines and their weight was appropriate – as was their activity level.

They unofficially dubbed it the Supermen study and showed that by reducing “inflammation” they could reduce the number of heart attacks and strokes. They concentrated on periodontal disease and rheumatologic diseases as sources of inflammation. They believed that angina and heart attacks and strokes did not occur because a blood vessel gradually narrowed much like a plumbing pipe clogged with hair and debris. They felt that soft lipid plaque under the surface in vehicles dubbed “foam cells” ruptured through the blood vessel wall into the lumen through the endothelial lining under the direction of inflammation in the body.

This breakthrough into the blood carrying portion of the blood vessel was perceived as a fresh cut or wound which was bleeding. The body’s natural response was to try and stop the bleeding by creating a clot. This clot occurred quickly in a small vessel and every living item downstream, not supplied by a collateral blood vessel, died from lack of oxygen and fuel to function. They treated the identifiable inflammation and felt that statin medications (Lipitor, Zocor, Pravachol, Crestor , Livalo and the generics) had an of- label quality that reduced inflammation as well as lowered the cholesterol.

I bought into that theory and incorporated these blood tests into the patient population most at risk and the appropriate age where prevention would make a major difference. Tests like hsCRP, Myeloperoxidase, Apo-B and others were used for screening. Finding the inflammation and treating it for men who met the definition for entry into the Supermen study was far more difficult. The whole theory of inflammation causing acute cardiac and cerebrovascular events was treated much like climate change, genetically modified foods and even vaccinations with a large degree of community doubt.

Last week at a major European Cardiology meeting the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) showed that by administering an anti- inflammatory medicine for three plus years at an appropriate dosage, we could reduce the number of heart attacks and strokes significantly. Using a monoclonal antibody, “Canakinumab” at 150 mg every third month they treated inflammation and reduced the number of events. The downside was the annual cost of this medicine currently stands at about $200,000 per year making it unavailable for most of us.

The surprising and startling finding was that it reduced lung cancers by 70% and other malignancies as well. The true finding in this study may be its use as a cancer weapon in the future. The study truly opened the door for research into new and less expensive approaches to treating inflammation. It validated inflammation as a pathway to vascular disease. Now we need to find a way to make that treatment affordable to all.

Coffee Consumption Lowers Mortality Risk

The online edition of the Annals of Internal Medicine, July 11, 2017 edition published an article from MJ Gunter using data from the European Prospective Investigation into Cancer and Nutrition that concluded that coffee consumption lowered patient mortality. The study looked at more than 520,000 patients from 10 different countries that were followed for 16.4 years. In a side study they looked at a group of 14, 800 patients and examined the correlation between coffee consumption and biomarkers of liver inflammation, function and health.

Patients who drank the most coffee had statistically significant lower all-cause mortality than individuals who did not consume coffee.  Patients in the highest group of coffee consumption tended to have significantly lower risk for mortality related to digestive diseases. Women coffee drinkers had a lower risk for cerebrovascular disease mortality and circulatory disease mortality but were at higher risk for ovarian cancer related mortality.

The researchers concluded, “Coffee drinking was associated with reduced risk for death from various causes.”

I will enjoy my coffee even more now. If only I could lay off the bagels and donuts that go with it.

PPI Use and Death Risk

In recent weeks we have seen articles linking the long term use of proton pump inhibitors such as Nexium (esomeprazole), Protonix ( Pantoprazole), Aciphex (Rabeprazole), Prilosec ( Omeprazole) with an increased risk of community acquired pneumonia, kidney disease, bone disease, cognitive dysfunction and increased risk of clostridia difficile infection (antibiotic related colitis). These drugs are commonly used short-term for the treatment of ulcers, gastro esophageal reflux disease, Barrett’s Esophagus, upper GI bleeding and H Pylori infections.

Often, after the prescribed treatment period, physicians try to discontinue the use of PPI’s but the patients have a return of their symptoms. With these medications now being sold over the counter, it is very difficult to get a symptomatic individual to curtail therapy even if the long-term risk is daunting.

I often attempt to switch patients to “old fashioned” antacids such as Tums, Rolaids, Mylanta, Gaviscon or even the H2 receptor blockers such as Tagamet and Zantac (Cimetidine and Ranitidine). All too frequently the response is that “my symptoms returned and only get better with the PPI.”

A study published in the British Medical Journal looked at data from the Veterans Administration data base for a period of two years, and selected a representative group of PPI users and non-users. They then followed them for 7-8 years.

Patients taking PPI drugs regularly had a 25% increased risk of death. There was no apparent reason why these medications led to a higher death risk. Further studies will be needed. The conclusion is take them for as short a period of time as possible.