Endoscope

                                                             Endoscope

                                                 PKGhatak, M.D.

The introduction of the minimal invasive surgery, also known as Endoscopic Surgery, has improved the surgical outcome in terms of patients' postoperative pain and discomfort and the operative results.

                            A surgeon is performing an endoscopy surgery.

The light travels in a straight line and that was the reason surgeons had to look straight down through an opening made by cutting a wide area of the skin, or through a natural opening. This allowed the surgeon to identify tissues before cutting and stitching back together after the operation.

By strategically placing mirrors, reflected images were examined, eg, the larynx and vocal cords by the ENT surgeons by using an indirect laryngoscope, which some physicians are still using today. The examination of the Lung-airways, or the esophagus and stomach, was a major undertaking. The patient's head and neck had to be brought in line with the rigid bronchoscope, or esophagogastroscope. And in a good number of cases, the patients lost a tooth or two and suffered bruises on the lips and tongue. Thanks to the scientists for inventing fibrotic fibers and the birth of the flexible endoscopy.

                          A patient is undergoing a rigid bronchoscopy.              

A short history of this development is recalled here.

In 1806, Dr. Phillip Bozzini of Germany used a rigid instrument to examine the stomach of a patient. An improved “open-tube” endoscope was designed and used by Dr Anonin Jean Desormeaux of France.

To shine a light from a burning candle down the tube inside the stomach was a major handicap. Sir Francis Cruise of Ireland developed an electric bulb in 1865, and soon electric bulbs were incorporated in such instruments.

Semiflexible scopes.

A German physician, Rudolf Schindler, working with George Wolf desinged the first semiflexible Gastroscope in 1932. The distal end of the scope was fexaible and had a system of lenses and the proxmimal end of the scope was rigid made of metals.

Fiber optics:

Light was used to signal between ships at sea, and not much for other types of communication. In 1840, Daniel Collodon and Jacques Banet proved that light could travel along a curved path of a water jet. Many decades later, it became known that light could also travel along a bent quartz rod. In 1940 doctors used illuminated plexiglass tongue depressors. A medical student, Heinrich Lamm in Germany, demonstrated image transmission through a bundle of optical fibers. In 1054, an article in Journal Nature, authors A. van Heel, H.H. Hospkin and Narinder Kapnay explained the science of transmission of images along a fiber optic cable by internal reflection.

Hirschowitz and Pollard of the University of Michigan visited Knapnay and discussed the application of fiberoptics to endoscopy. Three years later, they produced their fiber-optic gastroscope and Hirschowitz introduced the gastroscop on himself. In 1960, Hirschowitz received the patent of gastroscope and the American Cystoscope Manufacturing Inc., started producing fiber-optic gastroscope.

Internal Reflection:

The fiber optic cable has an inner core made of pure silica glass or plastic fiber, the diameter of which is 1/10 of a human hair. The core fiber is surrounded by glass fibers, called the cladding. The optical properties of the inner core fiber and the cladding are different.

The core fiber has a higher refractive index, allowing light to travel more slowly. The light travels along the core by bouncing off the wall of the cladding repeatedly onto the core and keeps the light signal inside. The total internal reflection allows light to travel with minimal loss of signals over a long distance at high speed, even when the cable is twisted or bent.

In 1970, Corning Glass researchers R. D. Maurer, D. Keck and P. Schultz developed fiber-optic wire with optical losses low enough for wide use in telecommunications.

The Nobel Prize:

The Nobel Prize for Physics in 2009, was awarded to C.K. Kao, W.S. Boyle and G.E. Smith for their work in fiber-optic and semiconductors. The Nobel committee remarked that the three scientists helped shape the foundation of mordan networked society.

Endoscopy surgery:

Technical expertise for minimal invasive surgery by endoscopy surgery requires special dexterity, advanced knowledge in anatomical structures from multiple lines of sight and their relationship with one another in a limited field of vision of the surgeons, in addition to several special instruments.

Three groups of instruments are essential.

1. Endoscope and with all its accessories.

2. 
                          Accessory instruments for Endoscopy surgery
   
   

3. Excellent illumination.

4. Imaging equipment and monitors.

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                                        Use of Ultrasound in Medicine

                                                 P.K. Ghatak, M.D.

Ultrasound is a portion of sound that is beyond human ears can hear. The human hearing range is 20 to 20,000 Hz, and the intensity 2 to 120 decibels (dB). A decibel named after Alexander Graham Bell, the telephone, telegram, and audiometer inverter.

Ultrasound is used in medicine in two separate fields.

1. Imaging.

2. Therapeutic.

The images are called Sonograms, and the process of generating the images is called Sonography or Ultrasound study.

There are many ways Ultrasound is utilized in the medical field. It will be discussed later in this article.

What is Sonogram:

The sound waves are generated by vibrating crystals. The desired diagnostic sound waves are directed to the organ or organs under examination. The sound waves after encountering a barrier reflect back some or nearly all sound waves back. These reflected waves are collected and a computer generates pictures in great detail.

The reflected sound waves are often called Echo and the images generated are called Echogram, for example, Echocardiogram. The Echo has a special quality, among the reflected sound waves, which must reach the human ears after some delays for it to be registered as a separate sound. This delay is called Impedance and the impedance is variable depending on the tissue, air and fluid; this characteristic allows sonography to construct an image.

Who introduced Sonography in medicine:

Dr. Karl Dusskil, a Neurologist used sound waves in 1942, in his attempts to locate brain tumors. He took this idea from studying a publication of an Italian scientist, Spallanzani who discovered bats use ultrasound to locate insects and this process is called Echolocation.

How it is possible to image brain matter which is encased in a cranium, made of bones.

It uses the same principle as is used in the Subtraction Angiography. If the parameters of ultrasound of the cranial bones are known then, they are subtracted from the final scan and the true image of the brain emerges.

The science behind the conversion of electricity to sound.

When asymmetrical crystals, eg, Quartz or Polycrystalline Ceramics are subjected to physical stress, they are polarized and generate electricity which is called Piezoelectric.

In a reversed situation, when these crystals are placed in an electric field, they begin to vibrate and generate sound waves. By varying the crystals, frequency and amplitude of the electrical field, the sound waves of various frequencies and variable strength can be generated.

Components of Ultrasound (US) instrument:

The basic components are ultrasound the Generator, also called the Transducer or Probe and the Receiver. The receiver is also incorporated into the transducer. The other parts are the monitor and controls. The transducer contains an assortment of crystals, and it comes in various shapes and sizes to fit the part of the body to be examined, eg, the neck is a small saddle-shaped gadget and a large gently curved transducer is used in the abdomen and pelvis examination.

In addition, there are specially designed probes for special locations to name a few - transthoracic esophageal ultrasound for examination of the left atrial chamber of the heart, and transrectal for examination of the prostate gland.

Ultrasound images:

US imaging is used for every organ system of the entire body, beginning from the time of conception to the last illness. US study is also useful for the evaluation of the functional status of an organ, detection of motion and direction of blood flow.

The special uses are called by different nomenclatures, eg, Echocardiogram, Doppler study of carotids or aortic valve, etc.

Advantages of Sonography:

1. The instrument is not expensive and the machine is portable.

2. There is no special reparation required for most studies and repeated examinations can be done to watch the progress of a disease or the state of recovery with treatment.

3. Patients are not exposed to radiation.

4. The technology is easy to teach and teaching facilities are locally available and not expensive.

5. The patient does not require to lie down for a US scan, in fact it is an advatade to scan when the patient is sitting or standing to detect small plural effusion or ascites, also, the venous obstructions in legs are better imaged is upright position.

Disadvantage:

1. Air does not produce echo and any structures next to a pocket of air in the body like the Pancreas and Lungs are difficult to visualize.

2. The image quality is very much dependent on the technical skill of the operator. It is like a good professional photographer setting up his camera for a portrait – the aperture, duration of exposure, power of the flash or lighting, etc. The image quality of US varies greatly on the frequency and strength of US generated by different probes, the depth and direction and the focal point; the angle the transducer makes with the body at the contact point. The direct end-on-view makes a clear image and increasing the angle makes the image fainter. The echo and artifacts can be manipulated to enhance the image brighter.

To minimize the adverse effect of the presence of air, in between the transducer and the skin of the patients, a water-based jelly is used. This jelly contains glycerin and propylene glycol in addition to water. It also provides a smooth surface for the probe to glide against the body and minimize patients's discomfort.

Types of Sonography.

A- Mode. A stands for Amplitude. A single pulse is transmitted through the body and the echo is collected and a linear image is produced. It is a one dimensional image.

B- Mode. B stands for Brightness. B-mode images are two dimensional, also called 2-D echo. The amplitude is in the X-axis, Y-axis is time. Using a proper probe and selecting the correct frequency of sound, depending on the depth of the organ located in the body, the technician should able to select echo of adequate amplitude to generate a good picture.

M-Mode. M is for Motion. Over a time period, successive B-mode echos are recorded and placed next to the previous one. Any moving part of an organ, eg, a beating heart, can be imaged like a moving picture taken by a camera put on sport mode.

3-D and 4-D Echo. The 3-D echogram is generated by taking the echo of the same organ or tissue from many angles and then stitching all of them together as one picture. It is like drawing a box on a flat sheet of paper, showing length, breadth and height. A 4-D echogram is a series of 3-D echograms  over a  time, depicting changes in volume or size over a specific time frame. The time is the 4^th dimension.

Other echograms for special purposes.

Trans Thoracic Echocardiogram (TTE). A narrow probe is introduced through the mouth into the esophagus and positioned just behind the Left Atrium and various aspects of this chamber are examined. This is useful in atrial fibrillation, pulmonary embolism, infra-atrial shunt and heart failure.

Trans-rectal. This is a standard for evaluation of the size, volume and consistency of the prostate gland and is utilized in transrectal biopsy of the prostate gland.

Transvaginal and or, Pelvic ultrasound: This is a standard imaging technology for the evaluation of every aspect of pregnancy, size and shape and growth growth of the fetus, placental health, blood flow, status of amniotic fluid and ectopic pregnancy. In other situations, any pelvic mass, ovarian pathology and ascites can be imaged with clarity.

Doppler Ultrasound:

Vesto Melvin Slipher discovered when a planet was moving away from the Milky Way, the light waves emitted from the planet, were less frequent and appeared Red than when the planet was moving towards the telescope of the observatory and the light waves had higher frequencies and appeared Blue.

In an Ultrasound study, the same phenomenon is utilized to detect whether the blood is moving forward in the blood vessels or falling backward. The Red Blood Cells (RBC) scattered US waves when hit by the US and the receiver records reflected waves and plots the blood movement towards the probe or away from the probe.

The Doppler US is useful in evaluating Aortic stenosis, Aortic and Mitral valve incompetence, Deep vein thrombosis of thigh and pelvic veins, Inferior Vena cava obstruction, the patency of the bile duct and many other uses.

Echocardiography:

A Swedish cardiac surgeon, Dr. Inge Edler, was searching for ways to investigate the Mitral valve function before surgical repair of mitral stenosis, which was a common malady of that time. A scientist named Carl Hellmuth Hertz was using Refected Palatinoscope for testing metal properties. These two scientists teamed together and took a moving echocardiogram of the Mitral valve. They published their findings in 1953, the echocardiogram generated was a 2-D motion image, and with this, the Echocardiography was born. They were awarded the Lasker Prize in 1977 but many scientists lamented that they deserved the Nobel prize in medicine.

What echocardiogram is used for:

This is a versatile machine for evaluating both the structure and functions of the heart as a whole and of its parts. The wall motion abnormality, following a suspected coronary event, indicates possible MI. Excess blood left in ventricular chambers indicates poor contralie function of ventricluar muscles as happens in heart failure. The functional status of all cardiac valves, the size and shape of valves, and the prolapse of valves due to papillary muscle damage can be easily detected. Individual ventricular systolic output or ejection can be studied by moment by moment and used every day for follow-up care in coronary artery disease and following bypass surgery. Interested readers may read many excellent articles published by the American College of Cardiology.

Medical Uses of Ultrasounds.

The use of the US is very extensive in daily medical practice. It can be summarized as

1. Diagnostic

2. Therapeutic.

3. Combination of the two.

Many of the diagnostic uses are already mentioned, in short, any diagnosis requiring an image can be accomplished by the use of a US study.

Physiotherapy:

Spain ankles, frozen shoulders, tendinitis, and tennis elbow are treated with low frequency US to increase the blood flow. The same principle is utilized in poor healing of bone fractures.

Tissue Biopsy:

Skinny needle biopsy for any nodules or growth, whether in a deep organ like the kidney or near the shin surface like the thyroid gland and breast tumors, the intervention radiologist accurately maps the tumor and its location then under its guidance introduces the needle and performs biopsy.

Stent placement:

In cases of deepening jaundice due to bile duct obstruction from any cause, including hepatocellular carcinoma, to immediately relieve unremitting symptoms of patients, the doctor locates the intrahepatic dilated hepatic duct by using the US and then threads a probe into it then inserts a stent to drain bile in the duodenum. This kind of procedure is done for obstruction of Cerebrospinal fluid circulation after an attack of meningitis /encephalitis. Renal pelvic obstructions or ureteral obstruction either from tumors or stones. Aspiration of pleura fluid and drainage, pericardial effusion,etc.

Central venous access:

Instead of a blind procedure of placing a Central Venous Line, using the US to locate the subclavian vein or innominate vein is much safer and less likely to produce any complications. In “hard to find veins” US helps to find a vein in the forearm to start an IV line.

Intra-arterial injection of thrombolytic agents:

In cerebral embolism or thrombosis, a Doppler study of the diseased vessel is used and then under US guidance the vessel is catheterized and the thrombolytic agent is infused.

Transdermal administration of medication:

The US is used to improve the absorptive capacity of a patch of skin and then a patch incorporated with medication is applied over it.

US in Surgery:

US energy is used in the ablation of tissues is called High Intensity Focus Ultrasound (HIFU). The high energy sound heats up the target tissue and destroys it, eg, aberrant ectopic focus in atrial fibrillation, Uterine fibroid and Prostatic hypertrophy. Other examples are Tracheal, Laryngeal papillomas, nasal polyps, vocal cord growth, etc

Skin Incision by using the US. Just like a laser beam in making a skin incision, US energy is also used for the same purpose.

Cauterization of bleeding vessels. An easy way to control bleeding is by using US energy.

In Eye surgery:

Phocoemulsifier- In cataract surgery, a needle is inserted into the cataract and it vibrates at US speed and emulsifies the lens. Then the derbies are suctioned out, then an artificial lens is inserted.

In Kidney stone and Gall stones:  Extracorporeal shock wave Lithriopsy.

The machine is called Lithotriptor and the process is Lithotriopsy. The body is immersed in water and shock waves are applied to the body to break up stones in smaller fragments and the gravels then pass out easily. The US waves are generated in several ways.

1. Electrohydraulic. The shock waves are created by making tiny sparks underwater between two metal points.

2. Electromagnetic. An electromagnatic coil generates shock waves.

3. Piezoelectric. Quartz or ceramic crystals generate the waves.

4. The other is light. Laser energy is directed toward the stones by breaking them up into small piec

During 1920 to 1940, European soccer teams used Ultrasound as a physiotherapy agent for the treatment of the injuries of their players. In 1958, the US was used in the OBGyn and soon became a standard technology used for various aspects of pregnancy, fetal development and ovarian pathology. The field became wide open with the introduction of Echocardiography and Doppler ultrasound.

Today, the US is the most versatile and often utilized technology in the medical field. Portable US instruments carried by the medical personnel on the nursing floors like a NoteBook and used for diagnostic purposes and also in the therapeutic armament,  In a urologists office, the post voided residual urine is determined in patients having voiding problems, just before the urologist sees the patient. Many cardiologist carry similar portable machine, at the point of service, for the evaluation of the many aspects of cardiac functions of their patients, whereas, the stethoscope is progressively becoming a museum piece. In the near future, all medical offices will be using a miniature portable Ultrasound like nowadays the weatherman talks about the weather on TV carrying a small NoteBook in his hand.

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MRI

                                                                    MRI.

                                                           P.K. Ghatak, M.D.

The magnetic resonance imaging (MRI) is one of the most advanced bioengineering technologies introduced in medical diagnostic armaments.

The first ever use of MRI took place in Britain in 1980, and then in the USA. Then MRI spread across the globe, limited in the countries by their inability to pay for the high price of the machine and non-availability of the infrastructure.

History of Magnetic Resonance:

Protons and Electrons when placed in an Electromagnetic field become excited, either due to absorption or emission of Electromagnetic Radiation. This phenomenon was first observed by the Soviet scientist Y.K. Zavoysky in 1944. The Nuclear Magnetic Resonance was detected by physicists Bloch and Purcell in 1946.

The Nobel Prize in Medicine in 2003 was awarded to Paul Lauterburg, of the University of Illinois and Peter Mansfield of the University of Nottingham, UK, for their discoveries in MRI. However, it must be understood that these two scientists based their work on the works of so many other scientists, and notable among them, are Felix Bloch and Edward Purcell, a pair of Nobel Laureates in Physics in 1952, for their discovery that certain nuclei could absorb and emit radiofrequency energy (Rfw) when placed in a magnetic field.

How MRI came to the medical field:

In 1970, Raymond Damadian discovered normal and cancer cells had different magnetic properties. John Mallard of the University of Aberdeen, Scotland used this principle in producing a full body image in 1970. Subsequently, this machine was used at St. Bartholomew hospital, London from 1983 to 1993. John Millard was given credit for the first ever use of MRI in the medical field.

Basic characteristics of human cells that are utilized in MRI.

Every living cell of the body contains water (H2O). The amount of water in normal cells of different tissues, and specially those cells that are diseased, has different levels of water content.

The hydrogen ion of the water is a Proton. In a strong magnetic field, the protons of the body can be manipulated to line up in one direction. A second magnetic field of different strengths and different orientations is pulsed several times a second. This energy knocks off the orientation of the protons and the protons take up another position. When the second magnetic field is completely switched off, the protons begin to go back to their original orientation and emit energy. The energy emitted by cells is proportional to their water content. This energy is collected and synthesized to generate MRI.

There are two standard images, one is T-1 weight image and the second is a T-2 weighted image. Additional images are the Proton Density (PD) image and Fluid Attenuated Inversion Recovery Image (FLAIR).

T-1 Image:

T-1 image relates to how quickly the nuclei of Hydrogen atoms return to their equilibrium state after being disturbed by an external magnetic pulse. It measures the time taken for the longitudinal magnetization of a tissue to recover. T-1 is also called the Longitudinal Relaxation Time image. Different tissues have different T-1 values, leading to varying rates of recovery and influencing the contrast in MRI images.

T-2 image:

The T-2 image sequences are controlled by the Repetition Time (TR) and Echo Time (TE) values. It measures the signal decay in the transverse planes. It is also known as a transverse relaxation image.

By manipulating the timing of RF pulses and sequences, the T-I and T-2 images are generated. T-1 images show normal anatomy in great detail. The T-2 images highlight the inflamed area and edema.

Proton Density Image:

The tissues with a high concentration of protons generate a strong signal and appear as the brightest image by minimizing the impact of T- and T-2 differences, by using a long TR and a short TE.

FLAIR image:

It is designed to suppress the signal from the cerebrospinal fluid (CSF) and make signals coming from diseased portions of the brain and spinal cord more intense. The fluid appears dark and the pathological parts stand out due to enhanced contrast.

How different parts of brain appears under T-1, T-2, FLAIR and PD views:

Part	T-1	T-2	FLAIR	PD
CSF	Dark	Intermediate	Darker	Dark
Fat	Bright	Very bight	Bright	Very bright
Air / sinus	Dark	Dark	Dark	Dark
Blood	Dark	Dark	Dark	Dark
Blood vessels	Dark	Dark	Dark	Dark
White Brain Matter	Intermediate	Darker than Gray matter	Intermediate	Darker than Grey matter
Gary Brain Matter	Darker than white matter	Intermediate	Intermediate	Intermediate
Bone	Dark	Dark	Dark	Dark
Bone marrow	Bright	Variable	Dark	Variable
Brain Stem	Intermediate	Intermediate	Intermediate	Intermediate

The MRI images can be synthesized in three planes – Axial, sagittal and Coronal Planes.

Contraindications and precautions for MRI:

The MRI suite is specially built because a very strong magnetic field is generated in this room. Any ferromagnetic metal, free or embedded in the body, will be magnetized and move towards the strong magnetic force.

This is a prime concern for patients having a cardiac packer, internal cardiac defibrillator, and inferior vena cava filters implanted in their bodies. The current manufacturers of these kinds of medical devices and have responded and now manufacture the devices with non–non-ferromagnetic metals.

The patients going for MRI should bring to the attention of the MRI personnel, if they have any of the following devices implanted in the body.

Cardiac pacemaker, implanted pacemaker, vascular shunt, Skull fracture, or craniotomy repaired with metals. Bullet or projectile injury, implanted simulators, deep-brain simulators, and vegas nerve simulators. Stimulators of the urinary bladder, spine, and nerves. Metal replacement of joints. Cochlear implants. Insulin pump and narcotic or any medicine delivery devices. Programmable shunts, aneurysm clips or coils. Venous filters. Continuous glucose monitor. A medication patch is applied to any part of the body. Any other devices attached to the body are not mentioned.

It is important to note that not all of these devices implanted in the body are contraindications for taking MRI images, but the radiologist must know beforehand so that proper precautions are taken during the operation of the MRI machine and also for the correct interpretation of the images.

Actual procedure:

The patient is taken to the waiting room of the MRI suite, provided with a gown and asked to change. Asked to remove jewelry, watches, credit cards and hearing aids, pins, metal hair accessories, pens, pocketknives, nail clippers multitool, and coins.

History of allergy to medication, iodine, shrimp and any IV medication or previous use of IV contrast.

The patient is taken to the scan room. The patient lies on a padded platform, ears are covered by noise-canceling ear pads and eyes are covered by a black eye patch. And provided with a panic button, just in case to call attention of the operator.

The patient is instructed to lie still and not to panic. The machine makes repeated loud bangs during scanning and parts of the machine come within inches of the parts under examination.

There are also open MRI machines. 

Duration of scanning:

It takes 45 minutes to an hour to complete a scan.

IV contrasts containing Gadolinium are often used to enhance the tumors or clearly delineate blood vessels or hematoma.

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footnote:

Ferromagnetic metals are Iron, Nickel, Cobalt, Gadolinium, Dysprosium, Terbium, Ferric Stainless Steel, Neodymium, and Iron-Boron Alloy

If you want to see how MRI looks like, copy this link and paste in the browser -

https://www.imaios.com/en/e-anatomy/brain/mri-axial-brain

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Bacteriology and Robert Koch

 

                             Bacteriology and Robert Koch

                                 P. K. Ghatak, M.D.

The birth of Bacteriology had to wait till the microscope was invented. But there is considerable controversy regarding who actually invented the microscope. In 1590, Hans Lippershey in Holland applied for a patent for a microscope and naturally, he was credited for inventing the microscope. At the same time, Antonie van Leeuwenhoek lived in the same town. He made a microscope of his own design. He found living organisms in the rainwater and then he began examining everything with his handheld microscope. In 1676, he reported his findings to the Royal Society of London, England. He reported observing various forms of small and smaller living organisms and he called them Animalcules. Medical society credited him for his inversion of the microscope.

Reproduction of the first compound microscope made by Hans and Zacharias Janssen, circa 1590. From the National Museum of Health and Medicine, Washington, D.C. (Image credit: Public domain.)                                         

The German scientist Ferdinand Cohn (1828 -1898), after years of pain streaking study of the various contradictory and confused publications on this subject, put his straightforward classification of bacteria in 1870. Many consider Cohn the originator of bacteriology but the majority gave the credit to Robert Koch.

The Spontaneous Generation of Life:

Louis Pasteur proved spontaneous generation was a myth.

People believed in the spontaneous generation of life. This was an age old concept from the observation that maggots grew on a piece of meat or cheese when left outside. Even Charles Darwin stated in his “Origin of Species” book that the human body could be conceived as a creature susceptible to the law of nature.

 Louis Pasteur (1822-95) proved that the microscopic living organisms were turning grape juice into vinegar and the spoiling could be prevented by killing the microorganisms by heating the grape juice and then rapidly cooling it. This process is known as Pasteurization

Lois Pasteur became a household name for his rabies vaccine. In 1885, he saved the life of a nine year old boy, named Joseph Meister, who was mauled by a vicious rabid dog. Pasteur administered his own laboratory grown vaccine. The Incubation period for rabies is 2 to 8 weeks, usually 3 weeks. If an adequate level of antibodies can be raised, in the body by administering a vaccine during the incubation period, then rabies would not develop. Pasteur's vaccine saved Meister, he did not develop rabies. Pasteur was a pioneer in attenuating the virus by successively passing it through a suitable laboratory animal thereby making the virus much less virulent but retaining the antigenic property, and then using that attenuated virus as a vaccine. He was working for several years with the rabies vaccine when Jeseph was brought to him by his mother,

Because Pasteur was dealing not only with bacteria but also with viruses, parasites and fungi he called the study of the microscopic organisms as Microbiology, instead of bacteriology.

Anthrax:

Like the wine industry in France, humans and livestock in Germany were dying from an unknown disease after a short illness. The task of finding the cause of illness and a cure fell on the shoulders of a multi talented medical doctor and head of bacteriology of Prussia (then in Germany), Dr. Robert Koch. He pretty soon found a rod shaped bacteria in the blood of the dead sheep.

He invented an oil immersion lens of a microscope for close up view. He developed ways to photograph the bacteria. He grew bacteria in pure culture in his specially formulated solid growing media of agar plate. By producing pictures of bacteria he left no doubt about the presence of the bacteria, Anthrax, was killing the animals. He collected soil and vegetation from the pastures detected spores of Anthrax and documented the full life cycle of anthrax. Spores were also infectious, if the spores were ingested or inhaled the spores germinated into the vegetative form and produced illness.  He recommended burning the carcass of the dead animal or buried deep underground, in order to prevent spore formation and limit the spread of anthrax.

The Germ Theory of Illness:

By providing direct evidence, he left no doubt that germs are the cause of illness and after he found Mycobacteria tuberculosis which was the cause of  TB, he put forward his Germ Theory of Illness.

Koch's Postulates:

After Koch discovered bacteria and medical communities accepted his germ theory, everywhere, many were finding bacteria and linked that bacterium to that illness. There were no checks and balances and no established criteria for verifying those claims. Koch designed 4 basic criteria for accepting a specific bacterium for a specific disease. It is known as Koch's Postulates.

Koch's four postulates are:

The organism causing the disease can be found in sick individuals but not in healthy ones.

The organism can be isolated and grown in pure culture.

The organism must cause the disease when it is introduced into a healthy animal.

The organism must be recovered from the infected animal and shown to be the same as the organism that was introduced.

The fundamental concept of Koch's postulates is still operative today with a few adjustments, for example, asymptomatic carriers like Typhoid Marry; recurrence of disease after apparent cure, as latent tuberculosis. Some human infectious disease has no real animal counterpart as in the case of cholera.

Asepsis:

Due to shear ignorance, doctors have killed thousands of patients over centuries, examples are plenty but to mention a few- bloodletting in Postpartum hemorrhage, antiphlogistic plaster in lobar pneumonia [https://digirepo.nlm.nih.gov/ext/dw/101299441/PDF/101299441.pdf] and performing an operation without scrubbing hands and delivering babies with unwashed hands.

Joseph Lister ( 1827 -1912).

He introduced soap and water washing hands and dipping hands in an antiseptic solution prior to vaginal deliveries. This simple hygienic method cut postpartum infection and death to a minimum.

Edward Jenner (1660 -1720)

He introduced the cowpox vaccine for the sure prevention of smallpox – one of the three curses of the ancient human civilization, the two others are Cholera and Leprosy.

Elie Metchnikoff (1845 – 1916).

In the early formative days of immunology, she demonstrated the phagocytic property of Neutrophils. Neutrophils devour bacteria before they have a chance to start an infection. The cellular immunity was born.

Emile Roux (1853 -1915) and Alexandre Emil Jean Yersin (1749 -1823):

They demonstrated the presence of the Diphtheria toxin in the liquid of the bacterial culture in broth.  This opened the door for an effective way to mitigate paralysis of muscles of breathing and swallowing.

Paul Ehrlich (1854 – 1915):

He found an effective agent for African sickness and introduced Salvarsan for the treatment of Syphilis.

Alexander Fleming:

Fleming introduced the first ever antibiotic - Penicillin. Penicillin saved thousands of lives by healing the wound infections, especially of the WW soldiers.

Just looking at the dates of a few pioneers in infectious diseases barely mentioned here, one can see that microbiology had a precocious childhood and became an adolescent by the end of 1900. Microbiology reached adulthood with the discovery of DNA and RNA analytic methodologies. The identification of microorganisms by stained slides and cultures is often unnecessary since rapid and more accurate identification is possible by detecting the specific DNA / RNA of bacteria and microorganisms by the PCR test.

                                                 Robert Koch.

The great German physician cum bacteriologist was born in Chausthal, Germany in 1843. He graduated in Natural Science from the University of Gottingen in 1866. Then Koch went to work under the direction of Jacob Henle ( the man after whom the Loop of Henle of the Kidney is known), and there he came in contact with another great German, Rudolf Virchow. He subsequently entered the medical college and graduated in 1866. He received a microscope from his parents as a graduation gift. That changed the trajectory of his passion and he immersed himself in the pursuit of finding the cause of diseases. After finding the bacterium Anthrax and later a mycobacterium for Tuberculosis, he proposed the Germ Theory of Illness. And put an end to the myth – the spontaneous generation of life.

He was awarded the Noble Prize in Medicine in 1905, for his research on tuberculosis.

A war broke out between Germany and France in 1870. He volunteered as an army doctor and served for 2 years. At the end of the war, he was made a district medical office in Wotszten, Germany (now in Poland) and accepted the position of the director of Bacteriology laboratory. His innovations in laboratory work are:

       1. New method of bacterial culture using solid media containing agar and gelatin.

2. Working with his associate, Richard Petri, he improved his solid culture media and made a disc shaped culture medium which is known as the Petri dish, which is still used in all bacteriology laboratories today.

3. Designed condenser of light for the microscope.

 4. Used oil immersion lens for further magnification of objects.

5. Developed Microphotography, direct photography through the microscope.

Anthrax and Koch's Postulates: - see the bacteriology section, above.

Cholera:

A cholera epidemic broke out in Egypt in 1883. The German government sent Dr. Koch to Egypt as the head of a medical mission with the task of finding the cause and control of infection. Because Dr. Koch was employed by the government, his research papers were not published in medical journals, instead, all his work on cholera was dispatched to the German government and those papers were made available to newspapers. He reported finding a comma shaped bacteria in the mucosal layer of the small intestine during autopsy, but not in the blood vessels or in the distal organs and tissue. Before he could find a suitable animal for the experiment and grow the bacteria in a pure culture, the epidemic in Egypt subsided. He requested and was granted to move to Calcutta for the continuation of his research where cholera was still raging.

He arrived in Calcutta in December 1883. He was able to culture the comma shaped organism. In one of his dispatches to the German government on January 7,1814, he stated that he had successfully isolated the bacteria in pure culture. That the autopsy findings and the nature of the bacteria had been the same as those in Egypt. He detected this curved bacteria in drinking water, ponds, rivers and in the clothes of cholera victims and relatives and even in the vegetation. He recommended boiling drinking water as a precaution. He did not find a suitable animal for further study of cholera. Dr. Koch found enteritis of the small bowel in cholera victims and predicted that the symptoms and fatalities in cholera were due to cholera toxins, and not due to septicemia.

The credit for identifying the cholera toxins and defining their properties went to Dr. Shambhu Nath Dey of Medical Collage of Calcutta. In 1959, he published his research paper in the journal Nature and described an endotoxin and another toxin- exotoxin of cholera. Endotoxin is heat labile and produces severe watery diarrhea and hyponatremia and death. Endotoxin activates the enzyme Adenyl cyclase which activates cyclic AMP. Cyclic AMP opens the pores of enterocytes of the entire small intestine, and the plasma of the blood is depleted rapidly and produces vasomotor collapse and death. The exotoxin is heat table, antigenic and has no enzymatic properties.

Tuberculosis:

Before Dr. Koch proved tuberculosis was a bacterial infection, people believed tuberculosis was an inherited disease. Koch was engaged in research on tuberculosis for many years. He developed a new bacterial staining technique by making the smears on a glass side and covering the smear with a coverslip and then treating it with Methylene blue and potassium hydroxide for 24 hrs. Using this stain, he was able to find a slender long bacteria. He went to isolate the bacteria and fulfilled all 4 criteria of Koch's postulates. He announced his findings in the Berlin Physiological Society meeting on March 24, 1882.

Tuberculin:

Koch continued to work on tuberculosis in order to find a cure. He announced discovering a substance that could arrest tuberculosis at an international medical congress in August 1890. He called it Tuberculin. He did not reveal the chemical nature of tuberculin. He extracted a liquid from the tuberculosis culture and then dissolved it in glycerine. But tuberculin failed totally to control tuberculosis, instead,  the tuberculin reactivated old TB lesions and produced severe allergic reactions. Before tuberculin use was discontinued 124 people died from reactions after receiving tuberculin injection.

Tuberculin Test:

Clemens von Pirquet (1874 -1929) a professor in medicine at the University of Vienna,        ( who discovered Serum sickness and Antigen-Antibody Reaction), developed a skin test using Koch's tuberculin, for the detection of TB infection. However, the skin test was unreliable due to the presence of contaminants.

Charles Mantoux purified the tuberculin and reintroduced the skin test, PPD             (purified protein derivative of tuberculin) in 1907 and named it the Pirquet test but now it is known as the Mantoux skin test used for detecting TB infection.

Koch's Phenomenon:

People who have active tuberculosis, if they receive tuberculin or BCG vaccine, develop severe allergic skin reactions, the skin at the injection site becomes necrotic and ulcerates. This is known as Koch's phenomenon.

Local Immunity:

Koch went to German New Guinea to investigate malaria. He discovered that the local people carry a high amount of malaria parasites in their blood but do not suffer from malaria, whereas, the visitors from other countries fell sick in a very short time. He explained this resistance to malaria in the local people was due to the development of immunity from prior infections. Investigators looked into it at a later date and found Koch was right.

Other areas of Koch's contribution:

In the early days of his long career, Dr Koch conducted the investigation of mitochondria function and discovered the Succinic acid in the cycle, what is known today as the Krebs Cycle.

He also contributed to detecting the cause of the following diseases -

Typhoid fever, Trypanosomiasis. Diphtheria, Syphilis, and Plague.

Where Koch was wrong:

Introducing Tuberculin without further scrutiny and giving the manufacturing right to a private company, was the biggest blunder of his distinguished career as an investigator.

He steadfastly believed that Bovine tuberculosis was not a danger to humans. It is a irony that his discovery of bovine tubercular bacillus gave birth to the BBC vaccine which stemmed the tide of childhood infection of TB.

BCG vaccine:

Albert Camette of the Pasteur Institute corroborated with Camille Guerin, a veterinarian who was suffering from TB, and began working on developing a bovine TB vaccine. After 230 subcultures in 13 years, they found a totally non-infectious TB bacillus but it retained its antigenic property. In 1921, they administered the vaccine to an infant whose mother was suffering from advanced TB. The vaccine saved the infant and the child remained healthy while the mother died of tuberculosis. That was the beginning of the BCG vaccine.

Downfall:

In 1893, Dr. Koch divorced his wife and within two months he married an actress. The fiasco with Tuberculin diminished him and people also accused him of greed for giving the manufacturing right of Tuberculin to a private company for money, at the same time, his research was supported by the German government. He was also accused of making attempts to sell the license to an American company for a large sum of money for manufacturing and marketing.

He suffered a stroke and died in 1910.

A final word:

Among the giants in public health and clinical medicine, none stands taller than this trio - Jenner, Pasteur, and Koch. Koch's talent was multidisciplinary from biochemistry to defining the parameters of immunology. Koch was an inventor of gadgets as well as a visionary. His work on tuberculosis alone will be remembered for centuries to come.

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Vaccination and Edward Jenner

                      Vaccination and Edward Jenner.

                        P.K.Ghatak, MD.

In 1980, the World Health Organization (WHO) declared Smallpox was eliminated from this earth forever. The world stopped to thank Edward Jenner for his gift, the Vaccine, to humanity.

It may seem strange but true that Dr. Edward Jenner was not the first person to notice having cowpox provided lifelong immunity to smallpox; nor was he the first to produce a vaccine against smallpox. That honor goes to ancient India, China and Africa.

People, from the beginning of human civilization, learned from experience that surviving a smallpox ordeal, protected them from the future smallpox.

In India:

They searched and found a way to introduce smallpox under a control condition. They called the process Tika and the court appointed people who administered Tika were called Tikadars. They collected pus from smallpox pustules of a patient and applied a drop of the material on the skin of the arm of an uninfected individual and made superficial cuts with a sharp scalpel in the skin, going through the pus. The process was not fully safe, some developed full-blown smallpox and died, however, the vast majority of vaccinated people were protected. The vaccination was only available for the royal family and high officials. Vaccination reached China through Tibet.

In China:

Chinese collected scabs from smallpox patients, dried and pulverized the scabs to a powder. They introduce this power in the right nostril of males by a silver blowpipe and in the left nostril of the females. The westerns called this a Variolation. China claimed variolation was an original Chinese invention.

In Istanbul, Turkey:

In 1718, Lady Mary W. Montague, the wife of British ambassador in the court of the Ottoman sultan in Istanbul, observed and was impressed with Variolation. She asked Dr. Charles Maitland, the embassy surgeon, to variolate her 5 year old son. This was effective. She wrote to her friends in England about variolation in order to protect people from smallpox.

In England:

Lady Montague returned to England and in 1721 she asked Dr. Maitland to variolate her 4 year daughter in the presence of royal physicians. This was also successful. Maitland was granted a license to practice variolation in England. In 1722, he successfully inoculated two daughters of the Prince of Wales. The process gradually spread all over Europe.

In a village in England:

In 1774, a farmer named Jesty, in Yetminster, knew from his own experience the protective property of cowpox. He deliberately infected his family with cowpox. Using the material from lesions on cow's udder and making scratches on the skin with a stocking needle and rubbing the material on the skin lesion. All of them survived the epidemic that was raging through the country.

An epithet is erected to memorialize the event, as shown below. [taken from BBC publication].

In another village:

In the 1760s, a country doctor, Dr. John Fewster, practiced vaccination in the village named Thronbury, Gloucestershire, England. His method of vaccination was almost similar to the one described earlier.

The virus:

The smallpox virus is known as Vaccinia. It belongs to Orthopoxvirus. Orthopox viruses are zoonotic (virus can infect humans from animals). There are 12 important orthopox viruses. Some of these viruses are species specific for one kind of animal, but most are infectious to wide varieties of mammals and birds.

Chickenpox, appears close to smallpox clinically, but in fact it is a completely different virus called Herpes varicella zoster virus.

Cowpox virus is known by CPXV.

Monkeypox virus is called Mpox virus.

Camel pox virus is called CMLV

Mice pox virus is called Ectromelia virus (ECTV).

Vaccinia virus is large, shaped like a brick, contains 170 to 230 genes. It is a double-stranded DNA virus. The centrally located gens are involved in replication within the cytoplasm of the cells, in contrast with most viruses which duplicate inside the nucleus. The peripherally located genes manipulate the victim's immune system and promote cell deaths.

Smallpox is called Variola in medical science. This term came from Switzerland in 570 AD, from a Latin word Varius or Varus meaning mark on the skin.

Chicken pox is called Varicella.

Dr. Edward Jenner:

Edward was born in 1749. Edward Jenner was Stephen Jenner's son, a priest in Berkeley, Gloucestershire, England. After completing his studies, at the age of 13, he went to work for a country surgeon. In there, he heard the story of dairymaids who had cowpox, did not contact smallpox and they had an unblemished face as a proof (in contrast with pox marked ugly face of survivors of smallpox). At age 21, he completed a two-year apprenticeship under the famous surgeon John Hunter and learned the systemic study of diseases. Thereafter, he returned to his own village and began a general practice. He studied the " mystery of cowpox in preventing smallpox." He understood the basic concept of immunity. He collected cowpox material and began inoculating people. Variolation and inoculation were often used interchangeably. [Inoculation a Latin word meaning graft, the term was derived from it]

He experimented on a 8 year old boy with pus obtained from lesions on the hand of a dairymaid. Two months later, in July 1796, he inoculated the boy again with pus obtained from a smallpox patient. The boy did not develop any illness. He wrote this case report and added his concept of immunity, and sent the paper to the Royal Society for publication. But the paper refused to publish it. He resubmitted the paper with additional cases. In 1797, the paper was published. He named his procedure as Vaccination.[vacca = cow, vaccinia = cowpox.]

He began publicizing and teaching doctors about vaccination, even to a point of ruining his own practice. In 1802, the British parliament granted him 10,000 pounds and again 20,000 pounds to compensate his time and materials. Jenner supplied anyone who requested the vaccine and often sent his assistants to teach the procedure. Jenner sent his vaccine to Benjamin Waterhouse of Harvard University. Dr. Waterhouse gave some of it to Thomas Jefferson. Due to Jefferson's efforts, the Institute of National Vaccine Program was set up in the USA.

In 1840, by the act of the British parliament, the following law was adapted:

     I. Vaccination was official policy, and variolation was banned for smallpox inoculation.

2. Government provided vaccine, made from cowpox, free of charge to all.

In the subsequent years, the vaccination against smallpox reached most European countries and in the new world. And the WHO took the vaccine to every corner of the earth.

Jenner was the first person to use a scientific method to control an infectious disease by the use of a live agent. In the late 19^th century, it became evident that immunity decline over the years and revaccination was necessary. Jenner suffered a stroke and died several months later in 1823 and was buried in a Berkeley church.

The WHO and Vaccinia Vaccine:

In 1959, the World Health Organization took up the challenge of eliminating smallpox. Soviet Union supplied the heat-stable, freeze-dried Vaccinia vaccine. On 8 May 1980, a little over 100 years after Jenner began vaccination in England, the WHO announced that the world was free of smallpox and recommended all countries cease vaccination.

No one knows:

Smallpox virus genome structure is deciphered and is utilized to trace interspecies migration of orthopoxvirus and mutations of the virus. It is a valuable tool for studying the source of an outbreak and how to start manufacturing vaccines. In 1939, scientists looked for the origin of the virus used for vaccination. To their surprise, they discovered that NONE of the 6 varieties of vaccine used in the worldwide vaccination program contained cowpox or horsepox virus. In fact, they have not come up with an answer as to when and how the switch of virus took place. However, the present vaccine has been found to be effective against Mpox. And new vaccines are on the way.