Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management
Can An Organ Transplant Change Someone's Personality?
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Claire Sylvia was an accomplished dancer when, at the age of 45, she was diagnosed with a rare incurable condition known as primary pulmonary hypertension, PPH. This disorder, which involves high blood pressure in the lungs, leads to enlargement of the right side of the heart and debilitating symptoms such as trouble breathing and extreme fatigue.
Although medication sometimes ameliorates the symptoms, the only effective treatment for severe PPH is a heart-lung transplant. And for Claire, as her symptoms worsened, such a transplant became her only hope for survival.
Three years after her cardiologist pronounced her grim diagnosis, Claire received a phone call notifying her that a donor had been found. An 18-year-old male was brain-dead following a motorcycle accident and his family had consented to donating his organs. Claire was about to become the first person ever to receive a heart-lung transplant at Yale-New Haven Hospital.
Claire's transplant was unique not just because she was the first person in New England to undergo such an operation, but also because of the changes that occurred following her surgery.
During an interview with a reporter on her third post-operative day, she was asked, "Claire, now that you've had this miracle, what do you want to do more than anything else." Her response surprised even her. "Actually, I'm dying for a beer right now." Claire later wrote that she was "mortified" by the words that came out of her mouth. She felt this was a flippant response to a sincere question, but even worse, she didn't like beer!
Later, she began wondering if perhaps some of her donor's personality traits existed within her. She developed a new taste for foods she did not like before receiving her new organs. In particular, she now had a strong desire for green peppers, which she previously disliked. Now she was adding green peppers to a wide variety of dishes.
Also, once she was allowed to drive, she headed straight to Kentucky Fried Chicken to satisfy her craving for chicken nuggets. This made no sense to her because she never ate fast food before her transplant.
Claire also noticed other changes in her personality. She no longer felt lonely, and she felt more independent. She was more confident, assertive, and even aggressive.
One night, she dreamed about a man named Tim and in that dream, she knew Tim would be with her forever.
More than two years after her transplant, Claire read the obituary of an 18-year-old man who was killed in a motorcycle accident just before she received her new heart and lungs. His name was Tim. Claire called Tim's family and scheduled a meeting so she could meet them.
When they met, Claire asked if Tim liked green peppers. His sister responded, "Are you kidding? He loved them, but what he really loved were chicken nuggets."
More EvidenceClaire's story would be amazing if it were the only story ever written describing personality changes in an organ recipient, ones that matched their donor's personality. But it's not.
Claire's story was released in 1997; three years later, neuropsychologist Paul Pearsall published a paper describing 10 heart transplant recipients who experienced personality changes that paralleled the personalities of their donors. These parallels included changes in preferences for food, music, art, sex, recreation, and career. In addition, some recipients identified the names of their donors and recalled specific events from their donor's lives.
One of Pearsall's cases involved a 5-year-old boy who received the heart of a 3-year-old boy. The recipient related: "I gave the boy a name. He's younger than me and I call him Timmy. He got hurt when he fell down. He likes Power Rangers a lot, I think, just like I used to. I don't like them anymore though."
The recipient's father explained neither his son nor his parents knew the name of the donor or his age. Later they learned the donor's name was Thomas, but his immediate family called him Tim. The recipient's mother added they had learned Tim died after falling from a window ledge while reaching for a Power Ranger toy.
More recently, my colleagues and I published the results from our study that found 89 percent of organ transplant recipients described personality changes following the transplantation of a variety of organs.
Where Are Memories Stored?Such stories and research findings seem implausible, particularly if we believe memories can only be stored in the brain. Plenty of research exists to support this view. The Spanish neuroscientist Santiago Ramón y Cajal suggested memories are stored in brain synapses in 1894, and the American Canadian neurosurgeon Wilder Penfield published research supporting this finding in 1937.
But could memories be stored in transplanted organs as well? Contemporary research suggests this may be possible. A previous review found memories can be stored in DNA, RNA, proteins, and epigenetic changes in cells outside the brain.
While these findings do not prove organ transplants cause personality changes, they do raise several questions: Where is memory stored? What types of memory could be stored in cells outside the brain? What factors contribute to personality? Can these factors be transferred with a donated organ?
More research is needed to investigate these questions and others. Such research would help organ transplant recipients better adjust to their new organs.
Facebook/LinkedIn image: Pormezz/Shutterstock
References
Sylvia, Claire. A Change of Heart. 1997. Little, Brown and Company, New York.
More referencesPhentermine, Oral Capsule
Phentermine is a prescription drug. It comes as an oral capsule, an oral tablet, and an orally disintegrating tablet.
Phentermine oral capsule is available as the brand-name drug Adipex-P. It's also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.
Phentermine is a controlled substance. Your use of this drug will be closely monitored by your doctor.
Why it's used
Phentermine oral capsule is only used short-term (for a few weeks) to treat obesity. This drug aids in weight loss in very obese and overweight people with certain health risk factors. These risk factors include high blood pressure, high cholesterol, and diabetes. This drug is used along with exercise, a low-calorie diet, and other behavior changes to lose weight.
How it works
Phentermine belongs to a class of drugs called anorectics. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.
It isn't known exactly how phentermine works to help you lose weight. It may work by increasing the release of chemicals in your brain that help reduce your appetite. This may help you eat less, which would aid in weight loss.
Phentermine oral capsule doesn't cause drowsiness, but it can cause trouble sleeping. It can also cause other side effects.
More common side effects
The more common side effects of phentermine can include:
If these effects are mild, they may go away within a few days or a couple of weeks. If they're more severe or don't go away, talk to your doctor or pharmacist.
Serious side effects
Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you're having a medical emergency. Serious side effects and their symptoms can include the following:
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.
Phentermine oral capsule can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.
To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you're taking. To find out how this drug might interact with something else you're taking, talk to your doctor or pharmacist.
Examples of drugs that can cause interactions with phentermine are listed below.
Drugs you shouldn't take
Taking certain drugs with phentermine may cause serious side effects. Don't take these drugs with phentermine. Examples of these drugs include:
Interactions that cause more side effects
Taking phentermine with certain medications may cause more side effects. Examples of these drugs include:
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.
This drug comes with several warnings.
Allergy warning
Phentermine can cause a severe allergic reaction. Symptoms can include:
If you develop these symptoms, call 911 or go to the nearest emergency room.
Don't take this drug again if you've ever had an allergic reaction to it or phendimetrazine tartrate. Taking it again could be fatal (cause death).
Alcohol interaction warning
The use of drinks that contain alcohol can increase your risk of side effects from phentermine. These side effects can include dizziness, feeling nervous and excitable, headache, hard stools or diarrhea, dry mouth, and not being able to sleep. They can also include decreased interest in sex or change in ability to have sex.
If you drink alcohol, talk to your doctor. You may need to be more closely monitored for side effects.
Warnings for people with certain health conditions
For people with history of primary pulmonary hypertension (PPH): You shouldn't take phentermine. Phentermine may make your PPH worse.
For people with history of heart disease: You shouldn't take this drug if you have a history of heart problems. These include stroke, arrhythmia (irregular heartbeat), heart failure, coronary artery disease, valve disease, and uncontrolled high blood pressure. Phentermine may cause a serious increase in your blood pressure. This may make your heart work harder. The extra stress on your heart may make your heart disease worse.
For people with history of hyperthyroidism: Tell your doctor if you have hyperthyroidism (an overactive thyroid). Phentermine may increase your thyroid activity. This may raise your thyroid levels even further.
For people with glaucoma: This drug may increase your eye pressure even more. This may cause permanent damage to your vision. Tell your doctor if you have glaucoma.
For people with diabetes: You may be able to control your diabetes better as you lose weight while you're on this drug. Your doctor may lower the dosage of your diabetes drugs.
For people with a history of drug misuse: This drug may be habit-forming. You shouldn't take this medication long-term. Tell your doctor if you have a history of drug or alcohol misuse.
For people with agitation: This drug may cause restlessness and anxiety and may make your agitation worse. You shouldn't take phentermine if you're agitated.
Warnings for other groups
For pregnant women: Phentermine is a category X pregnancy drug. That means two things:
Stop taking phentermine and call your doctor right away if you become pregnant while taking this drug.
When to call the doctorFor women who are breastfeeding: Phentermine may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.
For seniors: The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This raises your risk of side effects.
For children: This medication hasn't been studied in children. It shouldn't be used in people younger than 16 years.
All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:
Drug forms and strengths
Dosage for obesity
Adult dosage (ages 18–64 years)
Child dosage (age 16–17 years)
Child dosage (ages 0–16 years)
It hasn't been confirmed that this drug is safe and effective for use in children younger than 16 years. It shouldn't be used in children in this age range.
Senior dosage (ages 65 years and older)
The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This raises your risk of side effects.
Your doctor may start you on a lowered dosage or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.
Phentermine oral capsule is used for short-term treatment. It comes with serious risks if you don't take it as prescribed.
If you stop taking the drug or don't take it at all: You may not lose weight. If you take this drug for a long period of time and stop it suddenly, you may have extreme fatigue and depression.
If you miss doses or don't take the drug on schedule: Your medication may not work as well or may stop working completely. For this drug to work well, a certain amount needs to be in your body at all times.
If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:
If you think you've taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.
What to do if you miss a dose: Take your dose as soon as you remember. But if you remember just a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This could result in dangerous side effects.
How to tell if the drug is working: You should lose weight.
Keep these considerations in mind if your doctor prescribes phentermine for you.
General
Storage
Refills
A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.
Travel
When traveling with your medication:
Self-management
Your doctor will have you participate in an exercise program and follow a reduced-calorie diet while you're taking this drug. This should help you lose weight. Your doctor may also ask you to keep a journal of your food intake, exercise, and weight. This will help track your weight loss progress.
Clinical monitoring
Your weight and waist circumference will be monitored while you're taking this drug. This will tell you and your doctor if the medication is working to help you lose weight.
During your treatment, you and your doctor should monitor certain health issues. This can help make sure you stay safe while you take this drug. These issues include blood pressure.
Your diet
You should follow a reduced-calorie diet as directed by your doctor while taking this drug. This should help you lose weight.
Availability
Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead to make sure your pharmacy carries it.
Prior authorization
Many insurance companies require a prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.
There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.
Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.
Princeton Precision Health: An Interdisciplinary, AI-driven Approach To Tackling Big Questions About Health And Disease
Human health is influenced by an extraordinarily complicated range of factors, from genetics and socioeconomics to air quality and lifestyle factors like exercise. Princeton Precision Health (PPH) is taking aim at this whole complex picture, bringing together a unique combination of experts, giant datasets and advanced computational methods to gain a comprehensive understanding of how to make and keep humans healthy.
The initiative's 10 core faculty members include experts in sociology, psychology, computer science, engineering, genomics, environmental science, epidemiology and medicine, and PPH has awarded 22 endowment-funded seed grants to enable researchers from across the University to investigate health-related topics, such as the impact of technology on mental health and how computer vision tools can help diagnose autism.
Whereas faculty within a given academic department apply similar methods to different problems, "PPH aims to apply widely different methods and approaches to a common grand challenge," said Matthew Salganik, a professor of sociology and core PPH faculty member.
The grand challenge: to achieve a deep understanding of human health — at the molecular, individual and societal level — using sophisticated computational methods that integrate all factors of health to reliably predict outcomes for individuals and groups.
The PPH approach centers on developing artificial intelligence (AI) and computational models to crunch massive datasets and understand the mechanisms behind how different risks and variables interact to shape health outcomes, Salganik said. With no immediate clinical goal and no patients, "We can understand interactions among various factors affecting health, addressing hard questions that take longer to study.
"This approach integrates rigorous models from various disciplines to uncover the why behind these interactions, making accurate and scientifically testable predictions," he said. "The ultimate goal of precision health is to improve health for individuals and populations."
Olga Troyanskaya, a professor of both computer science and the Lewis-Sigler Institute for Integrative Genomics, directs PPH. "The genome — essentially a code made up of four different letters — is about 3 billion letters long," she said. "We have mapped the locations of most genes, but these account for less than 2% of the genome. The other 98% control when and how genes are activated. Until recently, our understanding of this 98% was limited. However, the emergence of deep learning models has transformed our ability to decode these mechanisms.
"We are now using AI models to uncover how genes are switched on and off and to predict when these activations will occur," Troyanskaya continued. "At Princeton Precision Health, we take this further by integrating genomic data with other critical information — such as socioeconomic and environmental factors — to provide a more comprehensive understanding of health outcomes. This integrated approach is helping us dig deeply into a wide range of health challenges, including infectious diseases, autism, kidney disease and depression."
The "perfect fit" for transformational changeWhile data has always driven health research, the sheer volume of health-related information and computational and AI advances make big leaps possible, said Mona Singh, a professor of computer science and the Lewis-Sigler Institute for Integrative Genomics and another core faculty member of PPH.
"The revolution that's going on with neural networks, foundation models, language models — these AI techniques have shown remarkable performance in a way that was unimaginable even a decade ago," she said. "It's really exciting to think about all the different ways in which AI can help precision health reach its goals."
And Princeton is ideally positioned to lead the charge, Singh said.
PPH Director Olga Troyanskaya (left) said the emergence of deep learning models has transformed the ability to decode "how genes are switched on and off and to predict when these activations will occur." An integrated, cross-disciplinary approach helps PPH dig deeply into health challenges including infectious diseases, autism, kidney disease and depression.
Photo by
Matthew Raspanti, Office of Communications
Princeton Precision Health (PPH) has distributed more than $2 million across 22 seed grants supporting 35 Princeton researchers, including these:
● Several researchers are partnering to determine if there is a causal link between widespread technology use and the rising mental health crisis in children and young adults — and, if so, what genetic, clinical, or environmental factors are contributing to the risk. Political scientist Jake Shapiro, neuroscientist Yael Niv, psychologists Molly Crockett and Kristina Olson, and PPH data scientist Manoj Kumar are working in this area.
● Ecology and evolutionary biologist Bryan Grenfell and computer scientist Adji Bousso Dieng are using new approaches and AI to understand individual variations in immunity and then extend this analysis more broadly to immune responses across entire populations.
● Sociologist Dalton Conley is investigating how a child's genetic predisposition for educational attainment, ADHD and depression affects parental mood, marital quality and developmental investments in that child.
● Clinical psychologist Erik Nook is using AI's large language models to quantify the most effective therapy for psychological disorders like anxiety and depression in teenagers, using thousands of hours of anonymized conversations between youths and therapists.
● Biologist Coleen Murphy is advancing research on what affects female reproductive aging by developing biomarkers for so-called "biological clocks" and exploring the social and environmental factors that influence them. She is collaborating with PPH's Dr. Debra Baseman, an OB/GYN.
● Computer scientist Olga Russakovsky is using visual AI tools to better understand neurodivergence, from anonymized clinical videos. To date, more than 20 peer-reviewed journal articles have acknowledged support from PPH since its debut in May 2022, on topics ranging from COVID-19 to depression to kidney disease.
Health beyond medicineFaculty from all four University divisions — Humanities, Social Sciences, Natural Sciences, and Engineering — already contribute to shaping the landscape of precision health research at Princeton. "Forty percent of faculty engaged in this research come from the social sciences and humanities, a key strength that sets Princeton apart," Troyanskaya said.
Sociologists, psychologists, electrical engineers, and computer scientists might be unexpected collaborators for health research, but that's part of PPH's secret sauce, she said.
"By integrating expertise, methods and perspectives across disciplines, we can unlock deeper and otherwise inaccessible insights regarding health at the individual and population level," said Erik Nook, an assistant professor of psychology and a PPH core faculty member.
It's no coincidence that fundamental discoveries are happening at a university without a medical school, said Dan Notterman, M.D., M.A., a professor of the practice in molecular biology and another core PPH faculty member.
"PPH allows for interdisciplinary collaborations in a way which might not be possible in the tightly focused environment of the medical establishment, which is more disease-oriented, and may not have the latitude to explore the nuances of human genetics, behavior and the environment that affect health," Notterman said. "At Princeton, we have the capacity to pursue research that requires a longer time frame and a broader, more diverse set of approaches."
That paradigm explains why the research facility for PPH, located at 252 Nassau St., has no fume hoods or petri dishes but instead a sea of laptops interspersed with small gathering spaces and an open presentation space for their popular speaker series.
An infrastructure to tap vast datasetsTo build their transformational understanding of human health, PPH researchers are drawing from some truly enormous datasets, including hundreds of thousands of complete human genomes and millions of disaggregated medical insurance claims — all with anonymized data and powerful safeguards around the records.
Datasets in health research present unique challenges for secure acquisition, storage and handling, said Salganik. No one researcher, however well resourced, could bring them all together and correlate the data from the disparate sources and disciplines. PPH brings together expertise — the data, clinical and research scientists — and resources to make this possible.
"Right now, an avalanche of diverse data — spanning genomic, molecular, social, behavioral and environmental factors, and clinical records — is being generated, but it remains siloed," said Salganik. "PPH can provide the infrastructure, expertise and collaborative framework necessary to acquire, integrate and analyze these diverse datasets."
PPH scientists have spent years getting these datasets to "talk to each other," said Kara Dolinski, the executive director of PPH. Clinical data and environmental data, for example, provide information about very different aspects of health and are measured at very different scales. But with extraordinary effort and cutting-edge AI and computational techniques, the researchers can link, for example, which lifestyle factors interact with a particular genetic predisposition for kidney failure.
"Human beings are complex," Nook said. "And PPH is transforming how we think about health research. It's not just about isolated studies of genetics, behavior or environment anymore. It's about integrating these factors at every level to gain a more comprehensive and predictive understanding of human health."
Training the next generationThe PPH core faculty members are all professors, and they are looking forward to sharing this new way of thinking about health with Princeton students. The professors are developing innovative courses to equip students across majors with the skills to address complex problems in precision health using data-driven, computational and interdisciplinary approaches. The students and early-career scholars will carry PPH's transformational approach into other academic, clinical and industry organizations — amplifying PPH's impact far beyond Princeton, said Nook.
"Princeton students have a thirst for truly interdisciplinary training that will equip them to address both foundational and applied challenges in health," said Troyanskaya, whose computer science class "AI in Precision Health" has enrolled students from majors including public affairs, anthropology, biology, chemistry and psychology — and has had a long waiting list each time she offered it.
"Our cross-cutting curricula and research, integrating data from across fields, will prepare students and early-career scholars to make transformative contributions in multiple health-related fields," she said. "Future doctors, yes, but also students interested in biomedical research, engineering, health-related socioeconomic and policy fields, and public philanthropy will all have access to the same modeling tools and interdisciplinary insight — and will all learn to speak the same language."
Guillermo Sapiro, a Distinguished Engineer with Apple, Inc. Who is now Princeton's Augustine Family Professor in Electrical and Computer Engineering, joined the Princeton faculty in large part because of PPH, he said.
"Before I joined Princeton, people would say to me, 'But Princeton doesn't have a medical school,' and I would say, 'Princeton has something better. Princeton gives its students interdisciplinary training to tackle modern challenges in human health, the knowledge and skills to grapple with data overload, disciplinary silos and the growing influence of AI,'" Sapiro said. "Through cross-cutting training, PPH will prepare students to make transformative contributions in medicine, biomedical research, engineering and health policy, empowering them to be leaders in diverse health-related fields."
Sapiro's research focuses on the relationship between health and human behaviors, including the use of tools like wearables.
PPH "is a super exciting initiative," he said. "Princeton's tradition of foundational, interdisciplinary research enables us to take a transformative quantitative and holistic view of human health — one that integrates cutting-edge science, data-driven insights and a deep understanding of the environmental, social and biological factors that shape health outcomes. In doing so, we are charting a path to transforming health in a way never done before."
Poornima Apte contributed to this story.
Previous Slide Next SlideSociologist Dalton Conley (center) speaks while Dr. Daniel Notterman (left) and sociologist Matthew Salganik look on, at a meeting of the PPH executive committee.
Photo by
Matthew Raspanti, Office of Communications
Panelists speak at a conference on campus co-sponored by PPH.
Photo by
Photo by Michael Paras for the Office of Communications
From left: Clinical psychologist Erik Nook, psychologist and linguist Adele Goldberg, PPH Executive Director Kara Dolinski and sociologist Matthew Salganik at a meeting of the core faculty committee.
Photo by
Matthew Raspanti, Office of Communications
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