One of the most dramatic and important achievements of the last century was the discovery of insulin in 1921-1922 in the University of Toronto. The patent remarkably got to be sold for a mere one dollar. Today a single vial of long acting insulin analogue costs almost $ 200 in the USA. North America has 7% of the world’s diabetic population but accounts for more than 50% of insulin sale, whereas China accounts for 25% of the world diabetic population but accounts for only 4% of insulin sales. Insulin sales could have been worth more than 20 billion dollars worldwide last year.
The story of the discovery has garnered a mythical hue. A 29-year-old surgeon Frederick Banting was assisted by undergraduate student named Charles Best in experiments with dogs that resulted in a crude insulin extract. The laboratory facilities were provided by the respected physiologist J.J.R. Macloed.The crude extract was refined by J B Collip, a biochemist. The crude insulin extract was injected in the first patient of diabetes in January 1922. This resulted in mild lowering of blood sugar, but the result was exciting enough for Eli Lilly in the US and Connaught Labs in Canada to begin industrial production of the wonder drug that would prove a life saver for patients of type 1 diabetes.
The sixth largest bank in Spain collapsed a few days ago. The failing of the bank is being compared to the collapse of the 150 years old Lehman Brothers in 2008. The collapse of the Spanish bank should be a matter of concern because the EU is the second largest economy in the world with the Euro being the second most used currency on the planet. Many investors have begun predicting the largest market crash sometime at the end of this year or early next year. More than 100 million working age Americans are unemployed. Warren Buffet apparently has $ 86 billion cash to buy cheap stocks after the anticipated great crash. Vehicle sales in the US have been going down each month the last 5 months in the US. The 2008 stock market crash will be a picnic compared to the imminent stocks collapse.
The future is not exactly rosy where the economy is concerned, particularly US fiscal health despite Mr. Trump’s recent more than $ 250 billion deal with the Saudis, a large proportion of which is money for arms and ammunition. America will continue with its spectacular efforts to amplify wars on the planet.
Sir James Black significantly contributed to the history of medicine by discovering not one but 2 great medicines. The second one was cimetidine a reasonably powerful anti peptic ulcer drug that he figured out would be effective based on the fact that histamine a powerful stimulant of gastric acid secretion was used as a diagnostic test to detect the susceptibility of a person to develop a peptic ulcer.
But probably more revolutionary was the development of propranolol in the 1960s by Black who studied medicine in Oxford. Black realized way back in the 1950’s that one way of tackling narrow arteries was to reduce heart rate and force of contraction of the human heart. In other words lower the need of oxygen. This led to his discovery of propranolol. Black won the Nobel prize in 1988 for “discoveries of important principles for drug treatment”.
Low cardiac output syndrome following cardiac surgery is not uncommon and is consequent to systemic inflammation by heart lung machine, vasoconstriction or reperfusion injury. Treatment is usually with parenteral inotropes such as beta-adrenergic agonists and phosphodiesterase inhibitors once low output sets in. The flip side with inotropes is that they can increase both oxygen consumption of the myocardium and trigger atrial or ventricular arrhythmias. Observational studies have reported higher rates of postoperative myocardial infarction, stroke renal dysfunction and death as compared to those patients not receiving inotropes.
Levosemenedan is a novel inotrope that does not increase oxygen consumption, has prolonged duration of action, and increases myocardial contraction by sensitizing calcium binding to troponin C. It also acts as a vasodilator. Small-randomized trials have shown postoperative mortality to be lowered with levosemendan as compared to dobutamine, milrinone or placebo. But these studies were not powered to detect survival with levosemendan.
For starters, The Times of India reported on August 11, 2014 that on April 2,1946 the Reuters correspondent in Melbourne, Australia cabled a short message that was carried by almost all newspapers a day later including the Times of India. The message read “ The Japanese Lieutenant Hisata Tomiyasu found guilty of the murder of 14 Indian soldiers and of cannibalism at Wewak (New Guinea) in 1944 has been sentenced to death by hanging, it is learned from Rabaul.
It is well known that their Japanese captors treated more than 10,000 Indian prisoners of war in the most inhuman way. There was no distinction between Indian officers and men. Often parties of haggard men would be taken away from the prison camps to the shooting range where they would be used as live targets for new Japanese infantry recruits to improve their shooting. Soldiers not killed in the firing would be bayoneted to death.
Japan had for long years evaded charges that its leading corporations enforced Nazi style labor during the Second World War. Mitsubishi with the famous triple diamond logo had long denied liability for thousands of Chinese serf labor in its coalmines. Mitsubishi in fact had argued that Japan had never invaded China. Japan captured Nanking in 1937 and in less than 6 weeks managed to slaughter more than 300,000 Chinese, one of the worst atrocities in history.
Fractional flow reserve (FFR) albeit highly accurate in determining the physiological relevance of an intermediate coronary block is still not widely used in most cath labs of the world. Data from 2008 to 2009 has revealed that FFR was used in only 6% of indeterminate lesions in the United States. Results of FAME and FAME 2 trials have shown significant reduction in major adverse cardiovascular events with FFR guided coronary intervention in patients with stable coronary disease. There was no significant reduction in mortality in the FAME trial.
Elective percutaneous coronary intervention (PCI) has always included at least an overnight stay due to fears of acute complications such as myocardial infarction, bleeding or vascular complications. Over the years interventional cardiologists have acquired greater confidence with improved hardware and better percutaneous techniques whilst doing PCI procedures. The risks of major adverse events have gradually been shrinking and are actually quite low. Most major adverse events occur within 6 hours of PCI. A same day discharge (SDD) protocol has gradually emerged after single center randomized and observational SDD experience. Overnight stay remains standard practice after a PCI.
A meta analysis collected data from almost 13,000 patients undergoing PCI. The study included 7 randomized trials (2738 patients) and 30 observational studies (10,065 patients). Clinical outcomes consisted of myocardial infarction, death, target lesion revascularization (TLR) and majority of patients suffered from stable angina.
Most patients with diabetes have little information on the effect of fruit on their blood sugar. The advice that fruits should be consumed sparingly has been promulgated for decades. There is however evidence that fruits do not only do not necessarily raise blood sugar but paradoxically reduces complications of diabetes and actually cut down mortality.
There are currently more than 400 million patients of diabetes, with a large chunk of them in India. India is the second largest producer of fruits in the world (China being the first). India grows about 40% of the world’s mangoes and papaya, and 25% of bananas. A portion of fruit contains 15-20 g of carbohydrate, while a can of Coca Cola or a medium slice of chocolate cake has 35g of carbohydrate. The sugar in fruit however is metabolically very different from refined sugar added to a cola or cake.
A mammoth Chinese study including 5 lakh people has concluded that eating fruit reduces development of diabetes by a significant 12% in people who did not have diabetes to begin with. The investigators also report that regular consumption of fruit in patients with diabetes resulted in significant lowering of mortality and complications of diabetes. The researchers conclude that their large epidemiological study in Chinese adults demonstrates higher fresh fruit consumption was associated significantly lower risk of diabetes and among diabetic individuals lower risks of death and development of major vascular complications.
The bioresorbable Absorb scaffold considered the holy grail of coronary intervention is now being pulled out from the commercial market in Europe. The stunning news is the culmination of sticky data emerging from recent randomized trials assessing the bioresorbable vascular scaffold (BRS), that have revealed that with this generation of BRS both efficacy and safety are questionable.
The ABSORB II trial reported a significantly higher rate of target vessel myocardial infarction last year. The ABSORB III trial further dampened enthusiasm by showing significant increase in target lesion failure. The last randomized trial to be published was actually terminated early because of increased stent thrombosis including late stent (BRS) thrombosis.
The AIDA (Amsterdam Investigator Initiated Absorb Strategy All Comers Trial) investigators randomly assigned 1845 patients to either receive a BRS (924 patients) or a metallic stent (921). Median follow up was 707 days. Target vessel failure (a composite of cardiac death, target vessel MI, or target vessel revascularization) occurred in 105 patients with BRS and in 94 patients in the stent group. Target vessel MI occurred in 48 patients in the BRS group but in only 30 provided metallic stents. Definite or probable stent thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (3.5% vs. 0.9%; p<0.001). This was a single blind, multicenter, investigator initiated non-inferiority trial.
I was taught right from my medical college undergraduate days that eating saturated fat was asking for trouble. Meat (red or white), cheese, butter and egg yolk were, for all practical purposes, proscribed. Repeated guidelines from the American Heart Association (AHA), American College of Cardiology and even the World Health Organization were clear that fats in general and saturated fats in particular were to be strictly avoided in order to prevent a heart attack. The message was to reduce fats to less than 30% of total calories consumed in a day with saturated fats to be kept well below 10%. The entire planet followed the dietary commandment from the 2 most powerful and respected cardiology associations of the planet.
The AHA declared way back in 1961 that saturated fats were bad because they increased blood cholesterol that in turn resulted in blockage of coronary arteries and heart attacks. The AHA astonishingly came to this conclusion based upon a hypothesis of one physiologist without a shred of hard evidence. Ancel Benjamin Keys, a physiologist who earned a PHD degree from Cambridge, was that single person who was able to stamp his Diet Heart Hypothesis into the consciousness of Dr Paul Dudley White who was a founder member of the AHA. Paul White was moreover looking after president Dwight Eisenhower who suffered his first heart attack in September 1955. Many middle aged Americans were succumbing to heart attacks in the 1950’s and the situation demanded answers from the health community of those times. Eisenhower had been the Supreme Commander of NATO and before that was the Supreme Commander of the allied forces that wrenched back Europe from the Germans in World War II. He had among other tasks to manage the brilliant generals George Patton and Bernard Montgomery. Eisenhower famously warned the American public in his farewell address from the “military-industrial complex”. President Eisenhower had no clue of the rapidly developing “health-pharmaceutical –industrial complex.”
Keys was able to launch his Diet Heart Hypothesis because there was little science available in the 1950’s that could explain the near epidemic of heart attack in middle-aged Americans. Keys presented his “Seven Countries Study” that displayed a clear association between eating greater amounts of saturated fats and deaths due to heart disease. The seven countries included USA, Japan, Yugoslavia, Netherlands, Italy, Greece, and Finland. There were however severe flaws in the methodology of his paper. Keys even managed to land on the cover of TIME magazine for his humongous contribution to science.
The association between mental stress and heart disease, which was for long speculated but never proven has final been nailed to a large extent by a study, published in the Lancet this year. The researchers from Harvard Medical School report that heightened activity in the amygdala, which processes emotions such as anger and fear, plays a major role in development of atherosclerosis.
The amygdalae (there are 2 of them on either side of the brain) prepare us for reacting to strong emotional stimuli. The amygdala is responsible to responses to both pleasure and fear. Amygdala means almond in Latin and the term was first used in 1819.
The scientific community is undoubtedly guilty of sending erratic and confusing messages on dietary prevention of heart disease. The public has been informed that eggs are bad, then that they are good, and currently they are considered neutral. Fats were taught to be bad, but now the public is informed that some fats are good (omega-3 and omega-6 polyunsaturated fats), that animal data are neutral while trans fats are awful.
Despite repeated advice over the years by nutrition and health experts less than 0.5% of countries consume optimal fruits (300g a day) and vegetables (400 g a day) a day. More than 80% of countries consume more than the recommended red meat prescription of 100g per week.
Atrial fibrillation (AF) is the commonest arrhythmia carrying the burden of cerebral embolus (CE), systemic embolus (SE) and aggravation of heart failure (HF). The risk of emboli is increased in persona with risk factors detailed by CHADS-VASc (Congestive heart failure, Hypertension, Age more than 75 years, Diabetes, Stroke, Vascular disease, Age between 65 and 74 Years, Sex category) score of 2 or more.
Traditionally the risk of embolism with subsequent morbidity and mortality has been managed by Warfarin, a vitamin K antagonist (VKA). Warfarin has always plagued treating physicians with a narrow therapeutic index, drug interactions, and need for repeated monitoring of efficacy by the International Normalized Ratio (INR). The ROCKET AF trial reported that only 55% of patients in the warfarin arm were in the INR therapeutic range.
Repeat coronary revascularization has always been found to be increased by routine follow up coronary angiography (FUCAG) in randomized trials done in the era of balloon angioplasty and percutaneous coronary intervention (PCI) with bare metal stents. But there was never any reduction in major clinical events. Myocardial infarction was reduced with angiographic follow up (AF) than with clinical follow up (CF) in BAAS (Balloon Angioplasty and Anticoagulation Study) and TAXUS –IV trials. Previous studies included low risk patients and hence impact of FUCAG in high-risk patients was unclear.
Treatment of high blood pressure reduces mortality, heart failure and heart attacks. The American Association of Physicians recently stated in their guidelines on treatment of hypertension in people over 60 years that it was enough to bring down blood pressure below 150 mm Hg to reduce risk of death, stroke and cardiac events. If a 60 year old has had a stroke or TIA then the target should be below 140 mm Hg to prevent another stroke, similarly in a patient with diabetes, metabolic syndrome or chronic kidney disease the target should be below 140 mm Hg.
All guidelines advocate lowering of high cholesterol and low-density lipoprotein (LDL) to reduce cardiac events, stroke and mortality. Numerous randomized trials have concluded that lowering LDL levels are beneficial for clinical outcomes.