Diary of a medical scientist

ah-thenah:

Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura (TTP) is a rare blood disorder characterized by clotting in small blood vessels of the body (thromboses), resulting in a low platelet count. In its full-blown form, the disease consists of the pentad of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic abnormalities, fever, and renal disease.”

Image 1: Peripheral smear from a patient with thrombotic thrombocytopenic purpura: Red blood cells are fragmented and appear as schistocytes. Certain schistocytes have the appearance of helmet cells (H). Spheroidal cells often are present (S). Occasional nucleated erythroid precursors may be present.

Image 2: A small platelet-fibrin thrombus is seen in a glomerular capillary above the arrow. This occurred in a patient with thrombotic thrombocytopenic purpura (TTP). This rare coagulopathy mainly affects kidneys, heart, and brain with small arteriolar thrombi. Acute renal failure can occur. The classic pentad of fever, acute renal failure, neurologic changes, thrombocytopenia, and microangiopathic hemolytic anemia is often present.

Sources: [x] [x]

mynotes4usmle:

WARFARIN-INDUCED SKIN NECROSIS
Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.[3]:122 Heparin-induced necrosis can develop both at sites of localinjection and - when infused intravenously - in a widespread pattern.[3]:123
In warfarin’s initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors II, IX and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels, it can lead to massive thrombosis with necrosis and gangrene of limbs.
Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of coumarins is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state.[1]
In one third of cases, warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis (blood stream infection) which also involves skin necrosis. These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency,[6][7] activated protein C resistance (Factor V Leiden)[8] and antithrombin III deficiency.[9]
Although the above theory is the most commonly accepted theory, others believe that it is a hypersensitivity reaction or a direct toxic effect.[1]

mynotes4usmle:

WARFARIN-INDUCED SKIN NECROSIS

Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.[3]:122 Heparin-induced necrosis can develop both at sites of localinjection and - when infused intravenously - in a widespread pattern.[3]:123

In warfarin’s initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors IIIX and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels, it can lead to massive thrombosis with necrosis and gangrene of limbs.

Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of coumarins is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state.[1]

In one third of cases, warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis (blood stream infection) which also involves skin necrosis. These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency,[6][7] activated protein C resistance (Factor V Leiden)[8] and antithrombin III deficiency.[9]

Although the above theory is the most commonly accepted theory, others believe that it is a hypersensitivity reaction or a direct toxic effect.[1]

Hi! I'm currently studying medical science in australia and i was wondering what's it like working in the hospital laboratory? did you have to do an honours degree because I was told that a bachelor degree is not enough to get a job because in australia a medical scientist occupation is not very stable due to lack of government funding. I intend to get into medicine so research is my backup. nice to meet you by the way!

Hi!
I’m not sure of the system in place in Australian hospitals, but in Ireland you would need an honours degree which has been accredited by the Academy of Medical Laboratory Science. You also need to have completed clinical rotations in an approved hospital before you can work as a medical scientist in a hospital. It’s important to note that you don’t need to do the rotations to work in industrial laboratories, though. The placement in a hospital is only needed if you plan on working on human diagnostic specimens.
I’m sorry if that’s not helpful, it’s just the way it worked out here for me. I must say that I love working where I do. I have been working in a histopathology lab now for almost 2 years and it has been far from boring. There is always something to learn - even people in their late 50s are still doing courses and progressing their careers! Some are even doing histodissection :)

If you want to ask anything else, feel free. I hope my personal experience has helped in some way!

How do lactose intolerant people while they are babies drink mothers milk ?
Anonymous

Lactose intolerance usually occurs after a baby has been weaned from breast milk to solid food, so it’s usually not a problem. It’s caused by a lack of lactase persistence alleles in their lactase gene. There is, however, a very small population with a condition called congenital lactase deficiency, where they are born without the ability to metabolise lactose in milk. They would not be able to consume the mother’s milk without the typical symptoms of lactose intolerance.

neurosciencestuff:

The anatomy of fear: Understanding the biological underpinnings of anxiety, phobias and PTSD 
Fear in a mouse brain looks much the same as fear in a human brain.
When a frightening stimulus is encountered, the thalamus shoots a message to the amygdala — the primitive part of the brain — even before it informs the parts responsible for higher cognition. The amygdala then goes into its hard-wired fight-or-flight response, triggering a host of predictable symptoms, including racing heart, heavy breathing, startle response, and sweating.
The similarities of fear response in the brains of mice and men have allowed scientists to understand the neural circuitry and molecular processes of fear and fear behaviors perhaps better than any other response. That understanding has spurred breakthroughs in treatments for psychiatric disorders that are underpinned by fear.
Anxiety disorders are one of the most common mental illnesses in the country, with nearly one-third of Americans experiencing symptoms at least once during their lives. There are generalized anxiety disorders and fear-related disorders, which include panic disorders, phobias, and post-traumatic stress disorder (PTSD).  
Emory psychiatrist and researcher Kerry Ressler is on the front lines of fear-disorder research. In his lab at Yerkes National Primate Research Center, he studies the molecular and cellular mechanisms of fear learning and extinction in mouse models. At Grady Memorial Hospital, he investigates the psychology, genetics, and biology of PTSD. And through the Grady Trauma Project, he works to draw attention to the problem of inner city intergenerational violence.
"If you look at Kerry’s work, it can seem like it’s all over the place — he’s got so many studies going on, and he collaborates with so many other scientists," says Barbara Rothbaum, associate vice chair of clinical research in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory. "But they are all pieces to the same puzzle. All his work, from molecular to clinical to policy, fits together and starts telling a story." A Howard Hughes Medical Institute investigator, Ressler was recently elected to the Institute of Medicine — one of the highest honors in the fields of health and medicine. He was named a member of a new national PTSD consortium led by Draper Laboratory. And he recently appeared on the Charlie Rose show’s brain series.
Panic attacks seem to tie the fear-related disorders together, he explained on Charlie Rose. Everyone experiences fear, which evolved as a survival mechanism, but it only rises to a clinical level when people are unable to function normally in the face of it. For instance, PTSD includes not only intrusive thoughts, memories, nightmares, and startle responses, but also the concept of avoidance, which may extend to other areas of the individual’s life.
"There’s a patient I’ve seen who was attacked in a dark alley," Ressler shared on the show. "Initially it just felt dangerous to go out at night, but after a while she grew afraid of men and couldn’t go to that part of town. Then she couldn’t leave her house, and finally, her bedroom. The world got more and more dangerous."

neurosciencestuff:

The anatomy of fear: Understanding the biological underpinnings of anxiety, phobias and PTSD

Fear in a mouse brain looks much the same as fear in a human brain.

When a frightening stimulus is encountered, the thalamus shoots a message to the amygdala — the primitive part of the brain — even before it informs the parts responsible for higher cognition. The amygdala then goes into its hard-wired fight-or-flight response, triggering a host of predictable symptoms, including racing heart, heavy breathing, startle response, and sweating.

The similarities of fear response in the brains of mice and men have allowed scientists to understand the neural circuitry and molecular processes of fear and fear behaviors perhaps better than any other response. That understanding has spurred breakthroughs in treatments for psychiatric disorders that are underpinned by fear.

Anxiety disorders are one of the most common mental illnesses in the country, with nearly one-third of Americans experiencing symptoms at least once during their lives. There are generalized anxiety disorders and fear-related disorders, which include panic disorders, phobias, and post-traumatic stress disorder (PTSD).  

Emory psychiatrist and researcher Kerry Ressler is on the front lines of fear-disorder research. In his lab at Yerkes National Primate Research Center, he studies the molecular and cellular mechanisms of fear learning and extinction in mouse models. At Grady Memorial Hospital, he investigates the psychology, genetics, and biology of PTSD. And through the Grady Trauma Project, he works to draw attention to the problem of inner city intergenerational violence.

"If you look at Kerry’s work, it can seem like it’s all over the place — he’s got so many studies going on, and he collaborates with so many other scientists," says Barbara Rothbaum, associate vice chair of clinical research in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory. "But they are all pieces to the same puzzle. All his work, from molecular to clinical to policy, fits together and starts telling a story." A Howard Hughes Medical Institute investigator, Ressler was recently elected to the Institute of Medicine — one of the highest honors in the fields of health and medicine. He was named a member of a new national PTSD consortium led by Draper Laboratory. And he recently appeared on the Charlie Rose show’s brain series.

Panic attacks seem to tie the fear-related disorders together, he explained on Charlie Rose. Everyone experiences fear, which evolved as a survival mechanism, but it only rises to a clinical level when people are unable to function normally in the face of it. For instance, PTSD includes not only intrusive thoughts, memories, nightmares, and startle responses, but also the concept of avoidance, which may extend to other areas of the individual’s life.

"There’s a patient I’ve seen who was attacked in a dark alley," Ressler shared on the show. "Initially it just felt dangerous to go out at night, but after a while she grew afraid of men and couldn’t go to that part of town. Then she couldn’t leave her house, and finally, her bedroom. The world got more and more dangerous."

neurosciencestuff:

New Device Allows Brain To Bypass Spinal Cord, Move Paralyzed Limbs

For the first time ever, a paralyzed man can move his fingers and hand with his own thoughts thanks to an innovative partnership between The Ohio State University Wexner Medical Center and Battelle.

Ian Burkhart, a 23-year-old quadriplegic from Dublin, Ohio, is the first patient to use Neurobridge, an electronic neural bypass for spinal cord injuries that reconnects the brain directly to muscles, allowing voluntary and functional control of a paralyzed limb. Burkhart is the first of a potential five participants in a clinical study.

“It’s much like a heart bypass, but instead of bypassing blood, we’re actually bypassing electrical signals,” said Chad Bouton, research leader at Battelle. “We’re taking those signals from the brain, going around the injury, and actually going directly to the muscles.”

The Neurobridge technology combines algorithms that learn and decode the user’s brain activity and a high-definition muscle stimulation sleeve that translates neural impulses from the brain and transmits new signals to the paralyzed limb. In this case, Ian’s brain signals bypass his injured spinal cord and move his hand, hence the name Neurobridge.

Burkhart, who was paralyzed four years ago during a diving accident, viewed the opportunity to participate in the six-month, FDA-approved clinical trial at Ohio State’s Wexner Medical Center as a chance to help others with spinal cord injuries.

“Initially, it piqued my interested because I like science, and it’s pretty interesting,” Burkhart said. “I’ve realized, ‘You know what? This is the way it is. You’re going to have to make the best out of it.’ You can sit and complain about it, but that’s not going to help you at all. So, you might as well work hard, do what you can and keep going on with life.” 

This technology has been a long time in the making. Working on the internally-funded project for nearly a decade to develop the algorithms, software and stimulation sleeve, Battelle scientists first recorded neural impulses from an electrode array implanted in a paralyzed person’s brain. They used that data to illustrate the device’s effect on the patient and prove the concept.

Two years ago, Bouton and his team began collaborating with Ohio State neuroscience researchers and clinicians Dr. Ali Rezai and Dr. Jerry Mysiw to design the clinical trials and validate the feasibility of using the Neurobridge technology in patients.

During a three-hour surgery on April 22, Rezai implanted a chip smaller than a pea onto the motor cortex of Burkhart’s brain. The tiny chip interprets brain signals and sends them to a computer, which recodes and sends them to the high-definition electrode stimulation sleeve that stimulates the proper muscles to execute his desired movements. Within a tenth of a second, Burkhart’s thoughts are translated into action.

“The surgery required the precise implantation of the micro-chip sensor in the area of Ian’s brain that controls his arm and hand movements,” Rezai said. 

He said this technology may one day help patients affected by various brain and spinal cord injuries such as strokes and traumatic brain injury.

Battelle also developed a non-invasive neurostimulation technology in the form of a wearable sleeve that allows for precise activation of small muscle segments in the arm to enable individual finger movement, along with software that forms a ‘virtual spinal cord’ to allow for coordination of dynamic hand and wrist movements.

The Ohio State and Battelle teams worked together to figure out the correct sequence of electrodes to stimulate to allow Burkhart to move his fingers and hand functionally. For example, Burkhart uses different brain signals and muscles to rotate his hand, make a fist or pinch his fingers together to grasp an object, Mysiw said. As part of the study, Burkhart worked for months using the electrode sleeve to stimulate his forearm to rebuild his atrophied muscles so they would be more responsive to the electric stimulation.

“I’ve been doing rehabilitation for a lot of years, and this is a tremendous stride forward in what we can offer these people,” said Mysiw, chair of the Department of Physical Medicine and Rehabilitation at Ohio State. “Now we’re examining human-machine interfaces and interactions, and how that type of technology can help.”  

Burkhart is hopeful for his future.

“It’s definitely great for me to be as young as I am when I was injured because the advancements in science and technology are growing rapidly and they’re only going to continue to increase.”

compoundchem:

science-junkie:

Antibiotic Resistance Is Now Rife across the Globe

Dangerous antibiotic-resistant bacteria and other pathogens have now emerged in every part of the world and threaten to roll back a century of medical advances. That’s the message from the World Health Organization in its first global report on this growing problem, which draws on drug-resistance data in 114 countries.
 
“A post antibiotic-era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century,” wrote Keiji Fukuda, WHO’s assistant director general for Health Security, in an introduction to the report. The crisis is the fruit of several decades of overreliance on the drugs and careless prescribing practices as well as routine use of the medicines in the rearing of livestock, the report noted.
 
Antibiotic resistance is putting patients in peril in both developing and developed countries, as bacteria responsible for an array of dangerous infections evolve resistance to the drugs that once vanquished them.
 
Gonorrhea, once well treated by antibiotics, is once again a major public health threat due to the emergence of new, resistant strains. Drugs that were once a last resort treatment for the sexually transmitted disease—which can lead to infertility, blindness and increased odds of HIV transmission if left untreated—are now the first-line treatment and are sometimes ineffective among patients in countries such as the U.K., Canada, Australia, France, Japan, Norway, South Africa, Slovenia and Sweden.
 
Drugs to treat Klebsiella pneumoniae—a common intestinal bacteria that can cause life-threatening infections in intensive care unit patients and newborns—no longer work in more than half of patients in some countries. And fluoroquinolones, drugs used to treat urinary tract infections, are also ineffective in more than half of sufferers in many parts of the world. Efforts to limit the spread of multidrug-resistant tuberculosis, malaria and HIV are also all under threat due to increasing bacterial resistance.
 
Although the development of resistance is to be expected over time, overuse of the drugs has accelerated the process by supplying additional selective pressure, noted the report, which was authored by an extensive team of researchers with WHO. And there are few drugs to replace the ones that are now ineffective: The last entirely new class of antibacterial drugs was discovered 27 years ago, according to the report.

Read more via scientificamerican.com

Infographic by who.int

Important stuff, and accompanied by a nicely done graphic.

Also, a graphic on the different major types of antibiotics would definitely be an interesting one - one for my to-do list!

ucsdhealthsciences:

Detecting Fetal Chromosomal Defects Without Risk Noninvasive sequencing is faster, cheaper and safer for mother and fetus, say researchers
Chromosomal abnormalities that result in birth defects and genetic disorders like Down syndrome remain a significant health burden in the United States and throughout the world, with some current prenatal screening procedures invasive and a potential risk to mother and unborn child.
In a paper published online this week in the Early Edition of PNAS, a team of scientists at the University of California, San Diego School of Medicine and in China describe a new benchtop semiconductor sequencing procedure and newly developed bioinformatics software tools that are fast, accurate, portable, less expensive and can be completed without harm to mother or fetus.  
“We believe this approach could become the standard of care for screening of prenatal chromosomal abnormalities,” said Kang Zhang, MD, PhD, professor of ophthalmology, founding director of the Institute for Genomic Medicine at UC San Diego and a staff physician at the San Diego VA Healthcare System.
The incidence of chromosomal abnormalities – in numbers or structure – is one in 160 live births in the United States, higher in other countries. In China, for example, the rate is one in 60 live births. The effects of these abnormalities, known as aneuploidies, can be severe, from developmental delays and neurological disorders to infertility and death. The incidence rate rises with maternal age, most notably after age 35.
Current diagnoses of fetal aneuploidies often rely upon invasive tests that sample amniotic fluid or placental tissues for fetal DNA that can then be analyzed using a variety of complex and expensive methods, including full karyotyping in which the entire set of chromosomes is viewed microscopically. While highly reliable, these invasive tests may cause infections in the pregnant woman and pose as much as a 1 percent risk of miscarriage and fetal loss. Results are not available for one to two weeks, extending anxiety for families waiting for information.
The new method relies upon massively parallel sequencing of cell-free fetal DNA using a benchtop semiconductor sequencing platform (SSP) called an Ion Torrent sequencer developed by Life Technologies. Cell-free fetal DNA is genetic material from the fetus that circulates naturally and freely in the mother’s bloodstream. It can be obtained through an ordinary blood draw, with SSP analysis achieved in less than four days.
To assess the SSP method, researchers tested 2,275 pregnant women. More than 500 participated in a retrospective analysis, undergoing full karyotyping to establish known chromosomal abnormalities followed by SSP testing. The remainder participated in a prospective study without prior karyotyping, and SSP testing results were then compared to karyotyping results. The sequencing and automated bioinformatics analyses were performed at iGenomics in Guangzhou, China.
“We used the retrospective study to establish the method and the prospective study to validate it,” said Zhang.
In the retrospective study, the researchers found that SSP detected multiple types of chromosomal abnormality with virtually 100 percent sensitivity and specificity compared to full karyotyping.
“To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using SSP,” said Zhang. “It provides an effective strategy for large-scale, noninvasive screenings in a clinical setting. It can be done in hospitals and outpatient clinics, more quickly and cheaply.”

ucsdhealthsciences:

Detecting Fetal Chromosomal Defects Without Risk
Noninvasive sequencing is faster, cheaper and safer for mother and fetus, say researchers

Chromosomal abnormalities that result in birth defects and genetic disorders like Down syndrome remain a significant health burden in the United States and throughout the world, with some current prenatal screening procedures invasive and a potential risk to mother and unborn child.

In a paper published online this week in the Early Edition of PNAS, a team of scientists at the University of California, San Diego School of Medicine and in China describe a new benchtop semiconductor sequencing procedure and newly developed bioinformatics software tools that are fast, accurate, portable, less expensive and can be completed without harm to mother or fetus.  

“We believe this approach could become the standard of care for screening of prenatal chromosomal abnormalities,” said Kang Zhang, MD, PhD, professor of ophthalmology, founding director of the Institute for Genomic Medicine at UC San Diego and a staff physician at the San Diego VA Healthcare System.

The incidence of chromosomal abnormalities – in numbers or structure – is one in 160 live births in the United States, higher in other countries. In China, for example, the rate is one in 60 live births. The effects of these abnormalities, known as aneuploidies, can be severe, from developmental delays and neurological disorders to infertility and death. The incidence rate rises with maternal age, most notably after age 35.

Current diagnoses of fetal aneuploidies often rely upon invasive tests that sample amniotic fluid or placental tissues for fetal DNA that can then be analyzed using a variety of complex and expensive methods, including full karyotyping in which the entire set of chromosomes is viewed microscopically. While highly reliable, these invasive tests may cause infections in the pregnant woman and pose as much as a 1 percent risk of miscarriage and fetal loss. Results are not available for one to two weeks, extending anxiety for families waiting for information.

The new method relies upon massively parallel sequencing of cell-free fetal DNA using a benchtop semiconductor sequencing platform (SSP) called an Ion Torrent sequencer developed by Life Technologies. Cell-free fetal DNA is genetic material from the fetus that circulates naturally and freely in the mother’s bloodstream. It can be obtained through an ordinary blood draw, with SSP analysis achieved in less than four days.

To assess the SSP method, researchers tested 2,275 pregnant women. More than 500 participated in a retrospective analysis, undergoing full karyotyping to establish known chromosomal abnormalities followed by SSP testing. The remainder participated in a prospective study without prior karyotyping, and SSP testing results were then compared to karyotyping results. The sequencing and automated bioinformatics analyses were performed at iGenomics in Guangzhou, China.

“We used the retrospective study to establish the method and the prospective study to validate it,” said Zhang.

In the retrospective study, the researchers found that SSP detected multiple types of chromosomal abnormality with virtually 100 percent sensitivity and specificity compared to full karyotyping.

“To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using SSP,” said Zhang. “It provides an effective strategy for large-scale, noninvasive screenings in a clinical setting. It can be done in hospitals and outpatient clinics, more quickly and cheaply.”