WHY WERE THE CATS GOING ROUND AND ROUND AND COMMITTING SUICIDE AT THE MINAMATA BAY?

     In 1956. cats in the Minamata bay walked around in circles, had convulsions , stumbled  around,  and seemed to commit suicide by jumping into the Minamata bay of Japan. This finding gave an early break in a series of patients with peculiar clinical features. What both the cats and the people had in common was that both ate the local fish. In 1956, a 5 year old girl developed what looked like encephalitis. 8 days later, her sister also developed similar illness. Altogether 54 patients were found to be suffering from Minmata disease. There were many similarities among these patients. Each one had eaten either fish or shell fish. Nearly all lived along the Minamata bay and were occupied in the fishing industry. Epidemiologists suspected the local fish as the cause but could not say why. To prove their theory, they brought cats from 100 miles away and fed them with the local fish. Same disease followed almost conclusively proving that eating the local fish was the cause.
      To understand "why" we have to go back in time . In 1906, a small factory was established in Minamata by the Chisso corporation - a carbide plant for the production of Acetylene. Fertilizer production was also added in 1920. In 1951, the plant began manufacturing acetaldehyde for the used in plastics which involved mercury oxide as the catalyst. Inorganic mercury used was methylated in an acetylene reaction tank forming methyl mercury which was highly toxic. This had to be recycled. As the recycling was expensive, the company started to dump the waste directly into the bay. Locals and the fishermen complained. The silence of the fishermen's onion  was bought by paying the fisherman's union to keep quiet. More than 100 tonnes of mercury was deposited in the bay contaminating the water and the marine life within. Only in 1940, mercury as the toxin was seriously considered after a similar poisoning from a seed company in Britain.
     The epidemiological research proved that the disease is not infectious or contagious. They said that dumping of the mercury waste was the cause and asked for a ban on fishing. Due to inaction, none of the recommendations were followed and many more  persons also became ill. In 1968, another similar outbreak was seen in another town of Japan - Niigata due to water contamination at Agano River. . The public became proactive and saw to it that the Chisso company halted the manufacture of acetaldehyde.
     Minamata disease had 2 major victims - the patients who consumed contaminated fish usually in large quantities and their offspring. Clinical features included ataxia, incoordination, Paresthesias, constriction of visual fields, tremors, dysarthria. Autopsy revealed neuronal damage involving the cerebral cortex and the cerebellum. A variety of Congenital Minamata disease was seen with cerebral palsy like features at birth due to intrauterine exposure to toxic mercury. Mental retardation, limb defects, cerebellar ataxia, dysarthria, chorea microcephaly, hypersalivation were seen. The features developed 6 months after the birth reflecting the sensitivity of the developing nervous system. to the industrial toxins.
     This episode taught us an expensive lesson - there are no shortcuts to waste disposal. Buying silence does not stop the effects of industrial pollution. This reflects the collective greed of the manufacturers, trade unionists and the society. More than 2 billion  were paid as compensation which negated all the concealed illegal savings! 

THE STORY OF A GIRL WHO WAS BEATEN BLACK AND BLUE BY HER FATHER - BUT WHY? HOW SHE WAS HELPED?

     It was just an ordinary day. Those were the early years of practice when the patients were few and far between. There was this banker, a promising one at that. Professionally he was doing very well. He had 2 daughters. Normally all 4 would come together for any one's consultation. I thought it was a happy family.
     That day they came for the elder daughter who was about  6 years old studying in the first standard. . She was weeping. Body had bruises. It looked like she had been beaten black and blue. On inquiry, I was in for a surprise. She had been badly beaten up by the father! This was a delicate issue and I had to tread the path very carefully. I asked the mother how she sustained the injuries. She promptly replied that the father her reprimanded her for her poor scholastic performance. I was surprised. I asked her what she meant. She said that the girl was very backward in studies and stupid. This was an irritating factor for the father who was busy with his profession. When he came home after a hard day's work, mother would complain to him about the daughter. Her performance in school was awful. Tuition teacher had almost given up. She never finished home work. She hardly ever did anything right in the school. Teacher and the mother were very worried. Feeling irritated after a hard day's work, the father would lose his cool and beat her up real bad!
     I decided to interact with the girl. She was shy. She was a bit reluctant to interact with me. After a little bit of coaxing, she opened up. I asked her her name and she replied correctly. I asked her to write it. She tried but was all wrong. I asked her about alphabets and she could not answer - unusual for a 1st standard girl. I wrote an alphabet - she read it wrong. I have a bad handwriting. So I now wrote in big size capital letter and she was still wrong. I told her that the alphabet was A and asked her to name something starting with that alphabet. She said Zebra! Obviously wrong. Then I showed her some pictures and asked her to identify them. A house, a tree and the like. She could not. She was bad in repeating what was tols. She could not recite even one nursery rhyme. I realized what the diagnosis was - Learning Disability - Dyslexia. Faculty of recognition of alphabets / pictures / numbers was all wrong. LBLD -Language Based Learning Disability could consist of calculation problems, reading problems, difficulty in auditory processing, repetition, and sometimes motor incoordination.
     I took the parents into confidence. I explained to them what dyslexia was. I also told them that the child was not doing it intentionally. They were surprised. They still felt that the girl was beyond education and therefore stupid whatever the label was. She was a abnormal child and a academic liability. It took me a lot of effort to tell them that there is indeed a solution. She would have to be trained in a special school and would require personal attention and training there. They were a bit reluctant because they saw it as a means of segregation and also felt that the child would be marked as 'different from the est' if she attended a special school. After counselling them and also sending them for special counsellers finally they agreed  with the suggestion o send her to a special school. I am glad to say the girl improved a lot and did well for herself.
     It is very interesting to note that children with these disorders get easily marked in an ordinary school. They manage well in their later life. Obviously the skills required for a career later are much less than those required in the years of schooling! The father went on to become a very successful a banker and held one of the topmost possible position in the banking industry just before his retirement.  This also shows that skills of very fine understanding of human nature and man management are not really necessary to be an outstanding professional . They get easily overshadowed by the extraordinary professional skills!
     

THE GINGER JAKE PARALYSIS - ONE OF THE CLASSICAL MYSTERIES IN THE HISTORY OF NEUROLOGY - HOW IT WAS SOLVED?

     In 1920, 18th amendment prohibited the sale and import of all alcoholic beverages. Attempts were made to produce legal alternatives to usual alcohol. A cottage industry started with this intention. Alcoholic extract of ginger was considered to be a patented medicine This liquid extract of Jamican ginger was called "Jake" and  could be sold legally.
     To curb the abuse of Jake, a standard formula was defined for its manufacture (USP) . The extract had to contain 5 grams of ginger per ml of the solvent. This resulted in a highly unpalatable bitter concoction.People were encouraged to mix this with soft drinks to make it taste better Agriculture department
occasionally boiled the product and studied the extract in detail including the weight of remaining solids.
     In order to make the product cheaper, alternative solvents were tried. Harry Gross, president of Hub products, used TOCP (TriOrthoCresyl Phosphate) thinking it is safe. Shortly after its release, thousands of people in Tennessee, Oklahoma, Kentucky suffered a mysterious disease manifesting as an ascending paralysis. An estimated 50000 people were stricken with paraparesis  or paraplegia.
     Dr. Epraim Goldfain was the first doctor to recognise it. In February 1930, he saw a man with a rapidly progressive foot drop. Within a short time he had 65 patients presenting with this mysterious affliction. Most of them were poor workers habitually consuming Jake. Working on this and other similar clues, the Maurice Smith and Elias Elvoe of NIH after analysing the samples determined that the toxic component to be TOCP These findings were confirmed by animal studies. Music industry picked it up and it went into 12 blues from 1928 to 1934. An United Victims Of Jamica Ginger Paralysis was formed with 35000 members belonging to the poor class.
     Later 105 people including 35 children died of Ethylene Glycol poisoning. Food, Drug and Cosmetics act was passed in 1938 to prevent any sale of medicines without safety testing. Die to weak laws, Gross got away without any Jail time till he again exported 640000 oz bottles to California after the ban He then served a 2 year jail sentence.
     Symptoms of Ginger Jake paralysis developed in a week of the intake starting with the abdominal cramps, later involving the legs and then the paralysis ascended. Sensory symptoms and  bladder involvement was rare. Some developed spasticity later suggesting a motor neuron involvement. Peripheral nerve and spinal cord were also seemingly involved
     The Ginger Jake paralysis taught us a lot about other neurotoxins also. Organo Phosphare Induced delayed Neuropathy was picked up later. Thus TOCP could involve peripheral nerve (long fibres) and the spinal cord. The Ginger Jake tragedy was one of the largest mass poisonings in the history of neurology, many others were  picked up later. These interesting cases included Peripheral neuropathy from Arsenic contaminated beer, Myoclonic encephalopathy mimiking Crutzfeldt - Jakob disease from GI preparations containing Bismuth; Encephalopathy and cerebral edema Triethyltin laced antibiotics to name a few.
     Needless to say the Ginger Jake was withdrawn and the disease disappeared!

THE PRICE THAT SERVETUS PAID FOR DISCOVERING THE SCIENTIFIC FACT AND TELLING THE TRUTH!

    " He who really understands what is involved in the breathing of man , has already sensed the breath of God" proclaimed the 16th century Spanish theologian and physician Miguel Servetus. Through the study of anatomy, Servetus sought rational explanation for the Bibilical passages placing the man's soul in the blood. He wondered how the breath of God reach the blood? 

     In 1553, he published his last work, the treatise Christianity Restored containing a passage describing the path of blood from the heart to the lungs. Servetus had discovered the pulmonary circulation. In doing so, he challenged the wisdom of Galen whose doctrines had survived the Middle Ages to become dogma. Galen believed that the blood mixed with the air in left ventricle( which he believed reached the left ventricle from right ventricle  through tiny pores in the midwall) to become "vital spirit" with the breath of God. We now know that this is not true - blood from the right side of the heart that is from the right ventricle goes to the left side through the pulmonary artery.

       Servetus challenged Galen's then conventional  view and said that the breath of God was produced by "another contrivance". He noted that the blood travelled from the right side of the heart to the left side by the way of a "lengthened passage through the lungs in the course of which it is elaborated and becomes of a crimson color. He was literally describing the pulmonary circulation. "After mixing the blood became a  fit  dwelling place for the vital spirit " and finally entered the left side of the heart. 

     This fact was not observed. When William Harvey described the blood circulation 75 years later, he did not know of Servatus's work. The work of this Spaniard went unrecognized till about 1700 when an English  surgeon discovered the passage. The theological doctrines declared heresy and Servatus had become a casualty of a religious battle. 

     It should be noted that Servatus lived during the period of Reformation, a period of religious ferment that led to the division of the Roman Catholic Church and the advent of the Protestantism. 

     Rebellious and outspoken, he published his first challenge to the church dogma at the age of 20. The work , however, opposed the fundamental doctrine of Trinity. This caused a furor resulting in Servetus fleeing from his house in Switzerland. He moved to Paris and studied Medicine under the pseudonym Michel Villanovanus. After  his graduation, he became the physician to the Archbishop of Vienne. His interest in theology continued to dominate his life. 

     Theologist John Calvin  at Geneva. was a prominent protestant reformer then. Hoping to get Calvin's  approval, Servatus sent him a copy of his Christianity Restored. Contrary to his expectation Calvin was so outraged that he vowed to get Servatus executed if he ever set his foot at Geneva. Undaunted, Servatus got 1000 copies of his book printed in France under a false identity. However he was discovered, seized and handed over to the christian authorities. He knew that his fate was sealed. He somehow escaped during his trial.

     He appeared in Geneva a few months later. Apparently, he was tempting the fate. Calvin had him arrested and put him on a trial for heresy. In the trial, he was found guilty of "infecting" his readers with "unhappy and wretched poison". 

     As the punishment, Servetus was burnt on stake on an October afternoon in 1553. A copy of his offending book was strapped to his waist. 

     I am sure you will agree Servatus was a true hero - he not only discovered the inconvenient truth but had the courage to go all the way to propagate it even if it meant death to him! Science progressed by the painstaking research and  heroic sacrifices made by him and the likes of him!

     

THE UNFORGETTABLE MANIPAL GLOSSARY!

     No one ever forgets their life at Manipal. Most memorable is the Manipal Lingo. The special terms we used there. I will share some of those that  I recollect.
    " IST" - Indian Standard Time - to denote the delay in the arrival for an appointment or a class. Sometimes shortened to IT - Indian Time.
    " No probs"- When a desperate friend asked "can you lend me ten rupees?" an equally desperate friend would answer "no probs - only wait till the month end!"
     Grandfather's road" - Usually mused by a motor bike rider to the pedestrian coming on the way "You think this is your grandfather's road, hah?"
      "Gone case" - Irredeemable / Irretrievable - "You are a gone case man, no attendance, how are you going to appear for the exams?"
     "Fierce" - Terrific / Fantastic - usually used for a good looking girl- "Boy, that girl, sure fierce man; looks like Marylyn Monroe"!
     "Double headed snake" - Untrustworthy / Sneaky - "He is a double headed snake, amn, he stirs up trouble by carrying tales between both the parties"!    
     "Down the valley" - Along the sloping road to Parkala- usually used to denote booze joints - "Hey, exams are postponed; we shall go down the valley and celebrate!"
     "Joint" - That is a tricky one with multiple meanings - In Anatomy - A movable junction between 2 bones; In common parlance " An eating place- that joint is no good, man!"; In the last usage "A rolled up paper or a cigarette containing Marijuana -have a joint I just rolled up one!"
     "Grass" - Multiple meanings - Grass of the KMC greens / vegetables. "He is a grass eater, man!"
     "Cherry" - A fruit - rarely used in that sense ; A good looking girl -"can I borrow your Brut, got a date with a cherry tonight!"
     "Fag" A slang commonly used for a cigarette
     "Pain in the ass" - Sombody being a nuisance - a painful situation about which nothing much can be done! "He is a pain in the ass, man!" Almost an equivalent is " Pain in the neck" which is less disturbing!
     "Heights" - The ultimate level of something  "Heights of stupidity - a real moron- half the students were described so! Hieghts of Insanity - word used to describe the other half of the Manipal students!
     "Bug" - A small unpleasant insect - a term used to denote persistent disturbance or irritation.
     "Take off" - To run away - "We got 3 holidays in a row, let's take off to Bangalore, man!"
     "Tube light" - A person taking a long term to understand simple things. "You are a real tube light, man!"
     "Solid"--  Very good / Fantastic / Terrific" "Hey, that girl is solid, man!"
     "Grub" - Rarely used to denote its true meaning (insect larva) - food / chow "Lets have some grub in the mess, man!"
     "Crash out" - Go too bed usually to sleep undisturbed - " Forget the movie tonight, man, I am going to crash out!"
     "Thengah" Used to denote a dumb person "You are a real tengah, man! You dont even know the way to the Manipal  Power Press!"
     "Lah" A staunch Malaysian word - Cant be defined ; but used with some other word, emphasises what is being said. "I can't come to thew movie, lah; I want to sleep, lah, verry sorrry lah!"
     "Dah" - Another typical Malaysian word- probably indicated darling(?) - No, dah, I can't come; Please lend me your notes, dah!"
     "UFO" - A powerful word meaning "get lost fast" - "UFO dah, I don't want you in this room!"
     "Wah wah " A word usually used to indicate extreme sarcasm / mockery
     "Check the scene" - to verify - "check the scene and tell me whether he is there!"
     "Kachang, lah" Another Malaysian terem used to denote making a task sound easier than it really is - A senior telling a junior (encouragingly) - Just study the tracts, lah, its kachang lah, you cna surely do it!"
     "Vie" - A slang for "to go". "Let's vie for a movie, man!"
     "Got contact" - Know the right people in the right places - "Do not worry about the attendance lah, got contacts lah!"
     "Crap" Rubbish / Nonsense - "boy, you must be nuts to read crap like that!"
     I hope you traveled back in Time Machine and lived a slice of life in Manipal once again in the same old days!

     Congratulations!
   
   
   
   
   
 

CAN COMMON LOW COST DRUGS BE USED TO TREAT CANCER? WHY THEN THERE IS NO HYPE ABOUT THESE?

     Cancer is an expensive disease. Investigations and management cost a lot of money. Insurance does not help much unless one knows the exact method of extracting that from the insurance companies. Availability  of inexpensive drugs is the dream of many patients. It would be even better if drugs which are inexpensive  and are already being used for other common  diseases can somehow be useful for the treatment of cancer. I am talking today of  exactly this scenario. I am sure these facts will leave you dumbstruck and seething with anger against the commercial nature of the pharma industry.
     METFORMIN  is the first drug I am addressing. Everyone knows Metformin. Doctors use it for Diabetes, Cosmetologists for obesity, Gynecologists for PCOS. It is a cheap drug with high safety profile and low cost. It is synthesized from French lilac and is found to limit the recurrence of particularly prostate cancer and early  breast cancer. In fact, the National cancer Institute of US and  Canadian Health services have joined hands for a large clinical study. Interestingly the way it works is by reducing the supply of excess glucose to the cancer cells (on which they thrive) and also affecting the mitochondria within the cells. It has even demonstrated promise in killing chemotherapy resistant cancer stem cells.
     The next wonder drug is CIMETIDINE . This H2 receptor blocker in fact is an OTC drug. This is shown to halt tumor growth when used in conjunction with the standard chemotherapy. It seems to work well in cell culture in human and animal studies. Benefit is seen in Colorectal cancer. It also showed a statistically significant improvement in overall survival.
     The next magic drug is NITROGLYERINE . Originally created to make explosives, it has been in use for more than 130 years mainly for the angina pectoris   Used in conjunction with the standard chemotherapy, it has shown to it has been shown to improve the response of many cancers including that of the lung and prostate.
     The next promising group of drugs is BETA BLOCKERS. Regularly used in the treatment of hypertension and arrhythmias, it has been shown to control the growth of a wide range of cancers, including those involving the breast, bowel, ovary, lung and melanoma. Lab studies have shown promise in the inhibition of progression of the breast cancer and metastasis. Animal studies showed promise in the response to chemotherapy. Humans studies showed promise in the decrease of progression of ovarian and pancreatic cancers. These benefits were seen with Propranolol, Atenolol, Metoprolol.
     The last drug I am going to name will leave you really surprised - It is a commonly used humble deworming agent,  -an antiparasitic drug  MEBENDAZOLE !  When used in in conjunction with the standard chemotherapy, it is found to reduce the tumor growth. It is found to help in the treatment of Brain and Adrenocortical cancers. It has also shown promise in metastatic adrenocortical and metastatic colon cancers. However, no human studies have been completed  upto now.
     The question therefore arises, if these drugs are indeed good, then why there is no focused research going on ? Why serious attempts are not being done to exploit this knowledge to the benefit f the mankind? One does not have to be an Einstein to guess the answer. There is no monetary returns for  the research / clinical trials / clinical usage of these drugs. Unless carefully planned studies are conducted, these drugs will be  soon  shoved to the corner and made invisible to the doctors and patients!

A TALE OF TWO PROFESSORS - BOTH WERE BRILLIANT; WHO WAS SMARTER?

     In the sixties and seventies, there were 2 professors - both brilliant, both were highly qualified academically. Both were gold medalists from London school of Tropical Medicine and Calcutta School of Tropical Medicine. Both were excellent teachers.
      One was a clinician with a highly successful private practice. The legend had it that he saw a patient anywhere - in the market, in a hotel, on the corridor and was very popular. The other professor was witty, with a sense of sarcastic humor. Both were good clinicians with good diagnostic skills. The popular professor  had studied at Rangoon.
      The popular professor  took classes after making sure sufficient students have assembled. If he felt the numbers were not sufficient, he would make the patient sit or stand on an elevated platform so that more people got to see and would get attracted and attend.  He would discuss loudly. The findings existent and non existent would be discussed and his unit PG s would endorse the same. The whole drama was very impressive as well as very educative. The sarcastic teacher on the other hand would take precise, concise , accurate classes. His sarcastic sense of humor would drive the not so intelligent students away. But the classes were highly appreciated. The same case would be presented twice - the sarcastic professor would diagnose Amoebiasis (his favorite diagnosis)and the popular doctor would diagnose Cardiac failure (his favorite diagnosis) and students got to learn 2 diseases!
     Then the popularity with the medical representatives. The popular doctor was their darling. He would oblige them with ready prescriptions. The sarcastic doctor would ask complicated questions at the end of which no prescriptions would follow unless he was thoroughly satisfied about the need and the quality of the drug. The distance  to which he threw the bottle or the tablets was inversely proportionate to the quality of the drug! The legend has it that a satisfied patient of his, an owner of a pharma company formulated Diethyl Carbamazine Citrate syrup to his specification for the traetment of Tropical eosinophilia.
     Then there was the Grand Rounds. Grand rounds was the ultimate event - a sort of show of strength - The chief accompanied by assistants, PG students, Interns, UG students, and students from other units would walk the long corridors together discussing various patients and other clinical problems. One group would have to cross the other person's wards where the group would intentionally slow down and have a show of a discussion. Sometimes they (unintentionally )met on the corridors with their respective groups resulting in verbal fireworks!In one such episode, the popular professor asked the sarcastic professor " I am sorry to hear that your son failed II MBBS exam. What happened? Was he not smart enough?"  The sarcastic professor was enraged. He coolly said "Thanks for the concern, professor.  It is not that he was not smart enough. If that was the case professor, I would have sent him to Rangoon for his studies!"
     The aftermath - The son of the popular professor went on t become a cardiologist and settled abroad.All  the 3 sons of the sarcastic professor became doctors and settled abroad. He died of cardiac failure and arrhythmias believing  all along he was suffering from Amoebiaisis!