Categories
Health and Disease

Management of Hypertensive Disorders in Pregnancy to Prevent Maternal and Foetal Mortality

Abstract

Hypertensive complications in pregnancy are increasing in prevalence and often cause significant impairments in maternal and foetal mortality and morbidity. Managing and treating these disorders aims to prevent serious cerebrovascular and cardiovascular effects in the mother without compromising foetal well-being.

Introduction

In the United States of America alone, hypertension occurs in roughly 6-8% of pregnancies among women ages 20-44. Associated complications of hypertension in pregnancies, including pre-eclampsia, eclampsia, and end-organ damage, are leading causes of maternal and foetal morbidity and mortality worldwide.  The main strategy in the treatment of hypertension in pregnancy is to prevent any cerebrovascular and cardiac complications for the mother whilst preserving the uteroplacental and foetal circulation and, limiting medication toxicity to the foetus.

Classification of Hypertension Disorders

These hypertensive pregnancy disorders are diagnosed using a variety of tests including blood pressure monitoring, PIGF (placental growth factor) test and urine tests for proteinuria (increased levels of protein in the urine). Blood pressure readings which are higher than 140/90 mm Hg must also be monitored closely.

  Preeclampsia and Eclampsia

High blood pressure and proteinuria of over 300mg, after 20-week gestation, are both characteristics of these disorders. The difference between eclampsia and preeclampsia is that eclampsia is a convulsive, more life-threatening form of pre-eclampsia, which affects 0.1% of all pregnancies. The disorder is thought to be caused by placental malperfusion resulting from an abnormal modelling of the maternal spiral arteries.

–   Gestational Hypertension

This disorder is diagnosed by measuring high blood pressure for the first time from a patient, after 20-week gestation alongside the absence of proteinuria. Gestational hypertension is significantly less dangerous than preeclampsia/eclampsia since the patient has not developed renal impairment, hence the absence of proteinuria.

–   Chronic Hypertension

Chronic Hypertension in Pregnancy is defined as blood pressure greater than 140mm Hg systolic and/0r 90 mm Hg diastolic, before pregnancy – however many women seek care for chronic hypertension only after becoming pregnant, before 20 weeks of gestation. This disorder is estimated to be present in approximately 3 – 5% of pregnancy and is increasingly more commonly encountered.

The 2 main risk factors contributing to this increasing prevalence of chronic hypertension include obesity and old age, which are also of increasing prevalence in pregnancy. Although many women with chronic hypertension remain stable during pregnancy and delivery, they are at a greater risk of several pregnancy complications, particularly superimposed preeclampsia, placental abruption, and preterm birth.

–   Chronic Hypertension with superimposed preeclampsia

This hypertension disorder is the new onset of proteinuria in the setting of hypertension before 20 weeks of gestation. Although, similar to chronic hypertension, this disorder is categorised separately due to the onset of proteinuria which is drastically increases the patients’ risk of HELLP syndrome (Haemolysis, Elevated Liver Enzymes and Low Platelets – a rare liver and blood clotting disorder that can affect pregnancy women).

Overall, there are four main organ systems which can suffer from possible acute complications of hypertensive pregnancies: Cardiovascular, Renal, Hepatic and the Central Nervous System (CNS). For mild to moderate hypertension in pregnancy, maternal risks are small, although they may be adverse consequences of high blood pressure in foetal cerebrovascular development. In contrast, early-onset and severe preeclampsia have a significant risk of later cardiovascular and renal morbidity and mortality, particularly for the mother.

Managing Hypertensive Pregnancy Disorders

Non-Pharmacological Approaches

In non-pregnant hypertensive patients, lifestyle changes and interventions, including weight loss and reducing salt intake, are often the course of treatment. However, currently, there is no evidence to show that these approaches, such as an exercise and diet programme, is effective in preventing and managing hypertension in pregnancy. A 2010 study concluded that exercise training could reduce preeclamptic features in animal models, both before and after gestation, however human randomised, double-blind trials have not had similar results. Similarly, although obesity is a contributing risk factor for gestational hypertension, no evidence institutes that weight loss interventions could prevent hypertensive disorders in pregnancy.

There are very few non-pharmacological approaches available for managing hypertensive pregnancy disorders, particularly the lack of evidence supporting such approaches. But, bed rest continued to be the most frequent advice for patients with preeclampsia, which has shown to lower blood pressure, promote renal function and, which all will prevent dire complications during delivery. Nevertheless, since the progression of preeclampsia to eclampsia is sudden and without prediction, patients with this condition will be admitted to hospital for observation, where pharmacological approaches are often used due to the severity of the condition.

The only definitive therapy for acute hypertensive syndromes (preeclampsia and eclampsia) is delivery. This is especially when urgent control of blood pressure is necessary, or when the risk of harm to the foetus and/or the mother is significantly high. Delivery must be postponed for as long as possible, to enable foetal maturation, particularly of the respiratory system – Premature babies often have underdeveloped lungs, where not enough surfactant has been produced, which can lead to lung collapse and respiratory distress. The decision for the time of delivery also determines the extent of preeclampsia and the risk of complications, dictated by the current gestational period, liver and renal function tests, coagulation tests, etc. Although delivery is seen as a definitive treatment, expectant management and close observation is appropriate, particularly for patients before 32 weeks gestation as the foetus will be underdeveloped and risk of mortality is high.

Pharmacological Approaches

The aim of pharmacological approaches during pregnancy is to prevent progression to severe hypertension and maternal complications, and to improve foetal development by prolonging the pregnancy.

The two main pharmacological agents to treat hypertensive pregnancies include anti-hypertensive agents and beta blockers. Anti-hypertensive agents are a class of drugs that are used to treat hypertension, which can be vasodilators or inhibitors of noradrenaline release. However, these medications should be ceased if diastolic blood pressure falls too low, which can result in maternal ischemia and potentially heart failure: low diastolic BP can restrict foetal blood supply, threatening dangerously low oxygen saturation levels.  Anti-hypertensive drugs are successful in reducing blood pressure but must be monitored closely to prevent low diastolic BP and to limit the rate of foetal growth restriction. In comparison, beta blockers medications are most preferred for the treatment of hypertension in pregnancies due to its proven safety and efficacy, and no association to adverse maternal or foetal outcomes.

However, the pharmacological management of hypertension in pregnancies remains controversial and understudied, particularly due to the various and complex factors affecting maternal and foetal wellbeing. Furthermore, increases in diversity and variability across patients’ clinical responses to medications require individualised assessments for dosing.

Conclusion

Hypertensive disorders is a common complication of pregnancy and due to the significant risk of morbidities and mortalities, the main issue with managing these disorders is identifying a balance between the maternal benefits from BP control and the foetal risks caused by intrauterine mediation toxicity and potential growth restriction. The treatment of hypertension may improve the risk profile for the mother and baby, and therefore delay delivery to increase survival rates for the foetus, but it does not cure hypertension, and preeclampsia, nor does it delay the progression to preeclampsia.

Bibliography

Brown, M.A. (2018). Hypertensive Disorders of Pregnancy. Hypertension, [online] 72(1), pp.24–43. Available at: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.117.10803 [Accessed 28 Oct. 2021].

CDC (2019). High Blood Pressure during Pregnancy. [online] Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/bloodpressure/pregnancy.htm. [Accessed 28 Oct. 2021].

Deak, T.M. and Moskovitz, J.B. (2012). Hypertension and Pregnancy. Emergency Medicine Clinics of North America, [online] 30(4), pp.903–917. Available at: https://pubmed.ncbi.nlm.nih.gov/23137402/ [Accessed 28 Oct. 2021].

Easterling, T.R. (2014). Pharmacological management of hypertension in pregnancy. Seminars in Perinatology, [online] 38(8), pp.487–495. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272602/ [Accessed 28 Oct. 2021].

Falcao, S. and Bisotto, S. (2010). Exercise training can attenuate preeclampsia-like features in an animal model. Journal of Hypertension, [online] 28(12), pp.2446–2453. Available at: https://pubmed.ncbi.nlm.nih.gov/20811291/ [Accessed 28 Oct. 2021].

Hladunewich, M., Karumanchi, S.A. and Lafayette, R. (2007). Pathophysiology of the Clinical Manifestations of Preeclampsia. Clinical Journal of the American Society of Nephrology, [online] 2(3), pp.543–549. Available at: https://cjasn.asnjournals.org/content/2/3/543 [Accessed 28 Oct. 2021].

Image 1 – https://www.wrh.ox.ac.uk/images/news/improving-the-prediction-of-preeclampsia/responsive_image?ratio=image&scale=w1140

Kattah, A.G. and Garovic, V.D. (2013). The Management of Hypertension in Pregnancy. Advances in Chronic Kidney Disease, [online] 20(3), pp.229–239. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925675/ – R1 [Accessed 28 Oct. 2021].

NHS Choices (2019). Newborn Respiratory Distress Syndrome. [online] National Health Service. Available at: https://www.nhs.uk/conditions/neonatal-respiratory-distress-syndrome/ [Accessed 28 Oct. 2021].

NICE. (n.d.). BNF is only available in the UK. [online] Available at: https://bnf.nice.org.uk/treatment-summary/antihypertensive-drugs.html [Accessed 28 Oct. 2021].

Preeclampsia Foundation (2020). Signs and Symptoms. [online] Preeclampsia Foundation. Available at: https://www.preeclampsia.org/signs-and-symptoms [Accessed 28 Oct. 2021].Vatish, M. (2016). Improving the Prediction of Preeclampsia. [online] Nuffield Department of Women’s & Reproductive Health: Medical Sciences Division. Available at: https://www.wrh.ox.ac.uk/news/how-to-predict-which-pregnant-women-have-suspected-preeclampsia [Accessed 28 Oct. 2021].

Categories
Commentary Health and Disease

Preventive Medicine – Does This Field of Medicine Have The Greatest Impact On Society?

Abstract:

Preventive medicine involves a combination of medical practices which are designed to avoid disease and illness, with the aims of improving quality and quantity of life. This proactive approach to patient care ensures sickness is minimised to enable patients to have the best chance of recovery to optimum health.

Introduction:

Throughout the years, medicine and healthcare have shown to be necessary for a society’s ability to function. Society’s functioning and stability suffer if there is a larger proportion of unhealthy people and, ill health hinders individuals’ productivity and prosperity in their roles in society. When illnesses and morbidities occur, societies rely upon trusted doctors and healthcare professionals to aid recovery – responsive actions taken to treat a sickness or disease. But what if there could be a medical field to prevent illness in the first instance?

Especially during the COVID-19 pandemic, preventive medicine has emerged to be one of the most important fields, focussing on promoting, protecting and maintaining health. Most medical fields are directed towards certain ages, illnesses or body systems – however, preventive medicine is not subject to these boundaries and, is a ubiquitous and relevant field in society. The three main aspects behind preventative medicine include health awareness, immunisations, and screening alongside testing. 

Health Awareness in Preventive Medicine:

Non-communicable diseases, such as Type 2 Diabetes mellitus and cardiovascular disease, have accounted for 89% of all deaths in the UK. This emphasises the significance of increased health awareness and preventive medicine required in society.  The risk factors of chronic diseases now are well-known and well-established – a set of lifestyle choices responsible for most of the main chronic diseases, including tobacco use, imbalanced diets and irregular physical activity. Clinical preventive care aids patients to alter lifestyle choices to reduce the onset of chronic disease and decrease the impact of the disease on patients. Awareness programmes, including mental health awareness, and non-communicable diseases awareness, permit ‘medicine [to bridge] the gap between society and science’ and reach out to individuals struggling with health, for support and improvement. 

Vaccinations in Preventive Medicine:

Continued and widespread vaccination programmes enable immunisation to infectious diseases, preventing illness, hospitalisation and mortality. For example, COVID-19 vaccines, such as the Pfizer, and Oxford-AstraZeneca vaccines, will help reduce the spread of the disease and are safer ways to provide protection, highlighting disease-control benefits of preventive medicine. Mortalities prevented also translate into long-term cost savings: between 2001-2020, immunisations since 2001 will have averted an estimated $350 billion in total global costs due to illness. This enables potential economic growth which can allow more investment in public services, particularly in healthcare, to further improve citizens’ quality of life.

Vaccination programmes greatly reduce the burden of infectious diseases, decreasing mortality and morbidity rates and enabling these resources and money to be used for other serious healthcare issues in countries.

Screening and Testing in Preventive Medicine:

Screening and testing benefit various fields in diagnosis and treatment. For example, developments of ultrasound, and other methods for prenatal diagnosis, enable obstetrician-gynaecologists to abort defective or unwanted pregnancies and create prenatal treatment plans. This increased birth rates globally and decreased maternal mortality ratios (MMR): previous studies show that MMR decreased by 38% between 2000 and 2017. These schemes also aid internal medicine physicians, who strive to discover diagnoses of complex medical issues in the care of chronic illness and comorbidities, by providing visual identification of damage in the body. Internists benefit from advanced testing schemes, which are effective for the emergence and evolution of new diseases. This enables the achievement of early, accurate diagnoses, improving patient outcomes. 

Future of Preventative Medicine:

Past medical research in preventive medicine has focussed predominantly on lengthening lifespan, however the resultant life extension, without reducing aging, has unsustainably increased the extent of aging alongside age-related diseases, plus social and medical costs. This suggests that the aim of preventive medicine should be re-focussed – preferably more towards ameliorating quality of life. 

Medical progress, particularly in the field of preventative medicine, will raise the questions of which aspect of healthcare should be invested in coming years and decades. Many may argue that a managed compression of morbidity should take place. This would entail switching the majority of medical research funding from the main causes of death/mortalities, such as cancer and heart disease, towards the main causes of morbidity, such as dementia, degenerative diseases and depression. This approach would preferably remain until the quality of life is sufficiently high to make it worth extending lifespan. 

This graph displays how, in Europe, life expectancy is continuing to increase more rapidly than healthy life expectancy (average number of years lived with good health and wellbeing), hence morbidity (average number of years lived with poor health and wellbeing) is slowly expanding.

If these approaches are successful, this would decrease the rate at which life expectancy is increasing and increase the rate at which healthy life expectancy is increasing, which will result in a compression of morbidity. This resultant compression of morbidity will benefit our health and the economy as social and medical costs will be reduced, and resources can eventually be switched back to expand life expectancy sustainably. 

Conclusion:

Preventative medicine can be perceived to have the greatest impact on society – It is a hub, linking other fields, to help see the outcome of the research in various fields come together. Technological advancements aid this field, influencing innovative solutions for disease prevention, diagnosis and clinical care, turning a tide on human disease – namely, to combat COVID-19.

Swetha Babu, Youth Medical Journal 2022

Bibliography:

World Health Organisation (2018) “Noncommunicable Diseases Country Profiles” https://apps.who.int/iris/handle/10665/274512

Working Party of the Royal College of Physicians (2005). “Doctors in society. Medical professionalism in a changing world.”  Clinical medicine (London, England), 5(6 Suppl 1)

World Health Organisation (2017). “Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001-2020.” Bulletin of the World Health Organizationhttps://doi.org/10.2471/BLT.16.178475

Image 1 – https://www.afro.who.int/sites/default/files/2019-01/imnz.jpg

Britannica, T. Editors of Encyclopaedia (2018, December 7). Obstetrics and gynaecology. Encyclopaedia Britannica.https://www.britannica.com/science/obstetrics

UNICEF Data (2020). “Trends in estimates of maternal mortality ratio (MMR), maternal deaths and lifetime risk of maternal death, 2000-2017.” https://data.unicef.org/topic/maternal-health/maternal-mortality/

Brown G. C. (2015). Living too long: the current focus of medical research on increasing the quantity, rather than the quality, of life is damaging our health and harming the economy. EMBO reports, 16(2), 137–141. https://doi.org/10.15252/embr.201439518

Image 2 – embr0016-0137-f4.jpg

Categories
Health and Disease

Xenotransplantation: Using Animal Organs to Relieve The Human Organ Crisis

By Swetha Babu

Published 2:35 EST, Sat November 20th, 2021

Abstract

The organ crisis is an ever-prominent issue as globally, the demand for healthy and well-functioning organs significantly exceeds the available supply. Xenotransplantation is a medical procedure whereby living cells, tissues or organs are transplanted from one species to another: a potential solution for the human organ crisis.

Introduction

In the United States of America alone, ten patients die each day while on the waiting list to receive life saving vital organ transplants.

Xenotransplantation can alleviate this issue, while also providing greater access of transplant organs to ethnic minorities and limiting rejection in grafts. The benefits and risks of this procedure will be evaluated to determine whether xenotransplantation is a potential solution to human organ shortages.

Potential for Xenotransplantation

 Organ Shortages 

Today, organ transplantation is mainly undertaken to treat severe failure of vital organs such as the heart, lungs, liver and kidneys. Population aging and increasing sedentary lifestyles will result in an increase of the prevalence of chronic diseases (such as Type 2 Diabetes Mellitus and Coronary Heart Disease) and, consequently, the demand for transplantation. The strain on transplant organ supplies will encourage advances in biomedical breakthroughs, particularly in diagnostics and genomics, to reduce the occurrence of diseases progressing to life-threatening stages where only organ transplantation is viable. However, currently, xenotransplantation is one of the most readily available options to lessen the organ transplant crisis.

Xenografts: Reducing Risk of Rejection

Xenotransplantation not only enables organ transplantation but also the transplantation of tissue and cells (known as xenografts). Various tissues such as animal bone, skin, and foetal neural tissues for xenotransplantation have been suggested to be viable. Animal-to-human transplantation of tissues is certainly less dangerous than organ xenotransplantation as the animal tissues do not have major blood supplies hence the immune response is less vigorous, and the surgical procedure is less risky. Meaning, less damage to the patient is expected due to the lower risk of rejection and infection.

Image 1

A common example of animal tissue xenotransplantation is biological heart valves. These valves are used since unlike mechanical valves, they are not associated with a higher risk of blood clots, so the intake of blood thinners is not required. Porcine (pig) valves, which are an example of successful xenografts in modern medicine, are frequently used to replace aortic and mitral valves in the heart to treat cardiac valve conditions such as valvular stenosis.

The benefit to Patients of Ethnic Minorities 

In addition, xenotransplantation could be hugely beneficial for patients of ethnic minorities, where locating a suitable organ match is difficult. To reduce the risk of rejection, donors and recipients are ‘matched’ – it is vital for the donor and the recipient to have a matching blood group and antigen tissues type which is generally difficult to coordinate with an ethnic minority group.

In 2017, figures revealed that 21 percent of people in the UK who died on the organ transplant waiting list were from a black, Asian, or ethnic minority background compared with 15 percent a decade ago. This problem is then heightened due to the fact that such ethnic minorities constitute a significantly larger proportion of the organ donation waitlist: patients of ethnic minorities are three to four times more likely to develop end-stage renal failure and therefore require a kidney transplant. The huge stress on the supply of organs for ethnic minority patients is clearly evident here, and xenotransplantation has the potential to curb this issue greatly.

Ethical Concerns Against The Procedure

Animal Mistreatment

Animal mistreatment and disobedience to animal rights is one of the most significant ethical concerns associated with xenotransplantation, and it is argued that xenotransplantation is a violation of nature to exploit animals for their organs.

The welfare of animals is of great concern as these animals will be subject to trials and experiments before xenotransplantation becomes an available medical procedure. In addition, since there is the possibility of virus transference from animal to human, these animals are raised with special diets and in supervised environments specified for their growth. This has resulted in ethical criticism, as keeping animals imprisoned in an area that is not similar to its natural habitat with synthetic food diets and without other animal interaction does not enable the animals to live naturally.

Xenotransplantation benefits humankind by potentially saving lives and elongating life expectancies to the detriment of animals.

Religious Concerns

From a religious perspective, a fundamental value is to protect and preserve human life.

Xenotransplantation could be difficult in some religious cultures, such as Judaism and Islam, as swine is prohibited to be consumed, and to receive an organ for transplant from this animal could be considered sinful, disobeying their religious ideologies. Hence, locating another appropriate animal species’ organs for transplantation into humans. However, according to some perspectives of Christianity, Judaism, and Islam, there are not any specific religious fundamental binding reasons which prohibit xenotransplantation to treat grave and life-threatening organ insufficiencies.

If a patient refuses xenotransplanted organs on religious or cultural grounds and still requires an organ to treat their condition, they may need to be prioritized for allotransplantation (human to human transplants), stimulating another ethical dilemma. In the event that xenotransplantation is a reality, the allocation of human and animal organs would have to be thoroughly evaluated, ensuring that allocation is based on clinical need and that the maximum number of people continue to receive transplant organs. 

Scientific Concerns Against The Procedure

Physiological Differences in Organs 

Size and longevity are two main issues regarding animal organs for xenotransplantation. For example, a pig heart or kidney, when of suitable size for donation, may still have the potential for rapid growth, and the rate of growth of animal organs compared to the growth of human organs is most likely to be significantly different. The differences in organ size will limit the range of potential recipients of xenotransplants. Furthermore, the natural lifestyle is roughly 15 years, and aging in xenotransplanted organs is unknown.

Introduction of Unknown Infections

Xenozoonosis is the transmission of infectious agents between species via xenotransplants and xenografts. Animal to human transmission of pathogens can be extremely rare but past occurrences include avian influenza.

The main reason for the increased likelihood of disease transmission in xenotransplantation is that the implantation of foreign tissues into the human body breaches the physical barriers that usually prevent the transmission of disease. This potentially leaves the recipient of the xenotransplant exposed to a myriad of unknown pathogens which will most likely leave the recipient severely immunosuppressed 

Impact on Psychological Well Being

It is possible for the transgenic animal organ transplantation into the human recipient to cause major psychological and personality issues for the recipient. In 2010, a study revealed that individuals can form certain perceptions about their physical shape and their identity, as they struggle with the acceptance of an animal organ transplant, providing controversies for both the patients and society.

Hyperacute Rejection

Hyperacute rejection occurs because the human antibodies in the blood recognize the foreign antigens on the cells of the xenograft/xenotransplant, which are cells of pigs and all other distantly related species, triggering a rapid immune response. These antibodies bind to the cells lining the blood vessels of the organs as blood flows through the animal tissues, which activates the complement system, attacking the xenograft/xenotransplant. White blood cells are also activated by the complement proteins, and within a few minutes, the animal tissues are reduced to a black, swollen mass: the xenograft/xenotransplant has been rejected.

Image 2
Example of hyperacute rejection after renal transplantation: Kidney is no longer able to function as tissues are destroyed.

Although hyperacute rejection can occur in allotransplantation, it is significantly more likely to occur in xenotransplant recipients as the tissues originate from an individual of a different species, resulting in notably different antigens on its cells’ surface. Hyperacute rejection is probably the most difficult scientific concern against xenotransplantation, however, many promising methods to tackle this issue have arisen. One method includes the genetic modification of pigs (transgenic pigs), where, when an organ of the modified pig is transplanted in a human, the human complement regulatory proteins on the cells of the pig organ to inhibit the activation of complement, inhibiting hyperacute rejection.

Application to Fundamentals of Medical Ethics

Autonomy

It is clear that the nature of informed consent is the permission of the patient about the procedure after receiving thorough information about the side effects, and in return, the patient will be safe from treatments that are incompatible with their beliefs or unwanted. Informed consent is infinitesimally significant when regarding medical procedures, particularly ethically and medically controversial procedures such as xenotransplantation.

Beneficence

With future scientific breakthroughs to reduce the risk of rejection and to alter the rate of aging of the tissues, xenotransplantation can become commercially available like allotransplantation, as the risk of further disease to the recipient will be much lower. However, in this age, xenotransplantation of organs remains extremely difficult as more harm to the patient will be done, even if the organ does not remain in the patient’s body on a long-term basis but just to elongate the patient’s life expectancy while they wait for a human transplant organ. 

Non-Maleficence

Currently, the risks associated with xenotransplantation potentially outweigh the benefits, mainly due to the lack of scientific uncertainty of whether the transplanted organ can function as desired in the recipient’s body. 

Justice

The physical risks of xenotransplantation can be life-threatening, hence,  the recipient should be under close follow-up for an indefinite period of time, which can affect many aspects of human life, including sexual relationships and nutrition. In addition, recipients may have compromised immune systems and an increased risk of contracting infections, resulting in complete isolation and quarantine from others. This situation is undoubtedly against the most basic human rights – freedom and the establishment of relationships with others.

Conclusion

Several solutions against medical issues concerning xenotransplantation have arisen in recent years, including genetic modification and using transgenic pigs. However, an abundance of research and funding for clinical trials is still required to ensure that the procedure is well understood for the safety of potential recipients.  

But currently, in the face of difficulties, such as the unmet balance between organ demand and supply, xenotransplantation may be an attractive option shortly as ethical concerns around anthropocentric views and animal mistreatment still remain. But, if society can accept the ethical obligations associated with xenotransplantation, this procedure undoubtedly has the potential to develop into a legitimate solution to organ shortages.

Swetha Babu, Youth Medical Journal 2021

References

US Food and Drug Administration. (2021, Mar 3.) “Xenotransplantation” https://www.fda.gov/vaccines-blood-biologics/xenotransplantation

Cascalho, M., & Platt, J. L. (2008). “Challenges and potentials of xenotransplantation” Clinical Immunology, 1215–1222. https://doi.org/10.1016/B978-0-323-04404-2.10081-8

Nuffield Council on Bioethics. (1996) “Animal-to-Human Transplants. The ethics of xenotransplantation” 5-6. https://www.who.int/ethics/en/ETH_Nuffiled_xenotransplantation.pdf

Morgan, M., Kenten, C., Deedat, S., Farsides, B., Newton, T., Randhawa, G., Sims, J., & Sque, M. (2016). “Increasing the acceptability and rates of organ donation among minority ethnic groups: a programme of observational and evaluative research on Donation, Transplantation and Ethnicity (DonaTE)” NIHR Journals Library.

NHS Blood and Transplant. Organ Donation. (2018, Jul 18.) “Government campaign will focus on urgent shortage of black, Asian and minority ethnic organ donors” https://www.organdonation.nhs.uk/get-involved/news/government-campaign-focus-on-bame-organ-shortage/

Behnam Manesh, S., Omani Samani, R., & Behnam Manesh, S. (2014). “Ethical issues of transplanting organs from transgenic animals into human beings” Cell journal, 16(3), 353–360.

Sautermeister, J., Mathieu, R., & Bogner, V. (2015). “Xenotransplantation-theological-ethical considerations in an interdisciplinary symposium” Xenotransplantation, 22(3), 174–182. https://doi.org/10.1111/xen.12163

Dooldeniya, M. D., & Warrens, A. N. (2003). “Xenotransplantation: where are we today?” Journal of the Royal Society of Medicine, 96(3), 111–117. https://doi.org/10.1258/jrsm.96.3.111

George J. F. (2006). Xenotransplantation: an ethical dilemma. Current opinion in cardiology, 21(2), 138–141. https://doi.org/10.1097/01.hco.0000203183.81534.f9

Image 1 – https://images.theconversation.com/files/196741/original/file-20171128-28856-5zra8q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=668&h=324&fit=crop

Image 2 – https://static.cambridge.org/binary/version/id/urn:cambridge.org:id:binary:20181009125204364-0075:9781107281981:61398fig16_3.png?pub-status=live

Categories
Health and Disease

The Increasing Prevalence of Autoimmune Diseases

By Swetha Babu

Published 11:16 PM EST, Mon August 16, 2021

Introduction

NIH (National Institutes of Health) have revealed that up to 23.5 million American citizens have an autoimmune disease and the prevalence is increasing. 80-100 various autoimmune diseases have been identified by scientists who also assume that at least 40 other diseases could potentially have an autoimmune basis.

Classifications of Autoimmune Diseases

No tissue or organ is exempt from autoimmune diseases: these diseases can affect various organs and organ systems, varying greatly among the individuals who have them, in terms of severity and responsiveness to therapy.

Autoimmune diseases can be either localized or systemic:

–       Systemic autoimmune diseases affect many organs and tissues simultaneously. Examples of systemic autoimmune diseases include scleroderma (affecting the skin, intestines, and less commonly lungs and kidneys) and Sjogren’s Syndrome (affecting salivary glands, tear glands, and joints.) 

–       Localised autoimmune diseases are organ-specific and remain in only a certain part of the body, but often can develop into systemic diseases. Examples of localized autoimmune diseases include Hashimoto’s disease (affecting the thyroid) and Discoid Lupus Erythematosus (affecting the skin). Discoid LE is an example of a localized disease that can progress into Systemic LE, affecting various organs such as the kidneys.

Increasing Prevalence

In the UK alone, the incidence of various autoimmune diseases is increasing at ranges between 3% and 9% year on year. This includes:

•       7.0% increase per year of rheumatic diseases such as rheumatoid arthritis

•       6.3% increase of endocrinological conditions such as type 1 diabetes

•       3.7% increase of neurological such as Multiple Sclerosis (MS)

•       4–9% increase per year of coeliac disease

In the United States of America, the prevalence of autoimmunity is also rising. According to researchers at the Allergy and Immunology section at Yale School of Medicine, in the last 25 years, there has been a 44% increase in ANA antibodies (antinuclear antibodies), which are antibodies that target themselves, with over 41 million people affected. These ANA antibodies presage autoimmune diseases such as lupus and autoimmune arthritis.

Image 1 –  ANA antibodies with fluorescent dye

Costs for hospitals to aid affected individuals continue to rise as the incidence of these diseases increases. Direct and indirect costs for just three autoimmune diseases alone (type 1 diabetes, rheumatoid arthritis, and multiple sclerosis) currently add up to more than £13 billion per year in the UK. The costs are significantly high due to the absence of treatments that cure autoimmune diseases and the likelihood for patients to develop major secondary diseases. Treatment of autoimmune disease focuses on controlling the autoimmune reaction with immunosuppressants: Corticosteroids are often used to control inflammation and suppress the immune response. Another medication such as pain medication is often prescribed to suppress symptoms of the disease.

Causes and Possible Reasons for Increasing Cases

The immune system is exceedingly complex, and research has revealed some potential triggers for excess immune responses.

Genetics, and Environmental Factors

The most simple theory is that as a result of a mutation, an individual inherited a faulty allele (a version of a gene, which codes for a specific protein). Hence, the protein does not form correctly and fails to function effectively. E.g., In Type I Diabetes mellitus, a mutation in particular protein results in the destruction of beta cells in the Islets of Langerhans, as the cells are wrongfully targeted and destroyed, which results in the inability to produce insulin.

Another genetic-related theory is that a certain genetic background makes an individual more likely to have a sensitive immune system, which, upon an encounter with a certain trigger (such as an infection or climate), sets off an autoimmune disease. Chilblain Lupus Erythematosus is an example of a disease that can be inherited but may only be expressed when an affected individual inhabits a colder climate.

Smoking and Drugs

Certain substances, particularly blood pressure medications or antibiotics, can trigger the onset of drug-induced lupus, which is a more benign form of the disease but can still greatly affect an individual’s daily activities. Statins can trigger the onset of statin-induced myopathy, which causes muscle weakness.

Weight and Obesity

Being overweight or obese raises the risk of developing autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis. The greater fat content and greater weight put stress on the joints, particularly the knees, and intruding fat tissues encourage further inflammation. The increasing global epidemic of obesity can contribute to the rising incidence of autoimmune diseases.

Research Advances to Lower Number of Cases

Clinical Trials

Knowledge about various autoimmune diseases and new therapies can be gained from clinical research studies, conducted with volunteers who undergo various medical tests. Clinical trials for autoimmune diseases include studying “the Pathogenesis of Chronic Inflammatory Rheumatic Diseases’” and studying “Patients Undergoing Therapy for Immune-Mediated Inflammatory Skin Conditions.” The purpose of these clinical research trials can enable various worldwide healthcare professionals to assess the safety and effectiveness of current and future therapies and to study how the onset and severity of the diseases can be dependent on inherited or acquired traits.

Laboratory Research

Researchers in laboratories investigate the molecular mechanisms of the immune response to understand the disease progression further whilst uncovering new treatment approaches. This information can enable patients’ risk for certain diseases to be recognized earlier and to provide appropriate treatments.

Translational Research

This involves linking both laboratory and clinical research as materials and information are exchanged and shared between these two disciplines. For example, demographic data and medical data from clinical trials can be studied together with blood samples and tissue samples to understand the diseases’ pathogenesis and progression to better target treatments.

Swetha Babu, Youth Medical Journal 2021

Conclusion

The increasing prevalence of autoimmune diseases and immune-related diseases continues to exert pressure on hospitals and to increase the costs for hospital treatments, due to the chronic nature of the diseases and the regular requirement for medication.

The ultimate goal of early diagnosis and therapy is prevention – before autoimmune diseases become a clinical problem.

Swetha Babu, Youth Medical Journal 2021

References

Lovell, D., Huang, B., Chen, C., Angeles-Han, S., Simon, T., Brunner, H. (2021) Prevalence of autoimmune diseases and other associated conditions in children and young adults with juvenile idiopathic arthritis. National Centre for Biotechnology Information. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978075/

British Society for Immunology. (2018, Nov. 26) Report reveals the rising rates of autoimmune conditions. https://www.immunology.org/news/report-reveals-the-rising-rates-autoimmune-conditions

Yale School Of Medicine. (2021, May. 20) Understanding Autoimmune Diseases. https://medicine.yale.edu/news-article/understanding-autoimmune-diseases/

Image 1 – http://blog.mblintl.com/antinuclear-antibodies-and-the-ifa-test

Johns Hopkins Medicine, Johns Hopkins Arthritis Center. https://www.hopkinsmedicine.org/health/wellness-and-prevention/what-are-common-symptoms-of-autoimmune-disease

Mayo Clinic, Clinical Trials: Autoimmune Diseases. (2021) https://www.mayo.edu/research/clinical-trials/diseases-conditions/autoimmune-diseases

Benaroya Research Institute at Virginia Mason, Autoimmune Diseases.

https://www.benaroyaresearch.org/what-is-bri/disease-information/autoimmune-diseases

Categories
Health and Disease

Phantom Limb: Perceiving the Invisible

By Swetha Babu

Published 3:02 PM EST, Sat July 10, 2021

Introduction

The incidence of phantom limb is reported to be as high as 60-80% in patients post-amputation. Phantom limb pain should be differentiated from residual limb pain (RLP), as the latter originates from the actual site of the amputation.

Unlike phantom limb, RLP is often a manifestation of an underlying source, such as nerve entrapment, skin infections, surgical trauma, etc.

Onset and Symptoms

The onset of phantom limb mostly occurs immediately after amputation, however, some are documented to onset after a few weeks, although, rarely months later. The rise towards maximal sensation and pain differs between patients, often due to the contrasting extent of trauma and amputation.

Phantom pains are often described as crushing, burning, tingling, and cramping. Phantom sensations can be categorised into three different types:

–   Kinetic (movement)

–   Kinaesthetic (position and shape)

–   Exteroceptive (other stimuli such as touch, temperature and irritations)

 Image 1

Pathophysiology Theories behind phantom pain

Peripheral Nerve Changes

Amputation can result in a great trauma to nerves and tissues surrounding the site of amputation. 

This damage disrupts the normal nervous signals involved with the missing limb. The proximal portions of severed nerves begin to form neuromas (benign growths of nerve tissue), and the nerves become hyper-excitable, resulting in spontaneous discharges of impulses – pain and other sensations are experienced. 

Brain Changes

There has been significant research into cortical reorganisation, and it is a commonly cited factor in phantom limb pain. Cortical reorganisation refers to how the brain ‘re-maps’ the sections of the brain, adapting to significant stimuli. This can result in stimulation of nerves in the residual limb and the surrounding areas, causing the experience of pain and sensation in the missing limb. There is also a correlation between the extent of cortical reorganisation and the amount of pain that the patient experiences. 

An example of Cortical Reorganisation in response to amputation:

Psychological Factors

Sensations and pain could be influenced by memory of the incident, memory of pain proceeding the amputation, mood state, and a variety of other social concerns. In addition, circulating epinephrine within the body resulting from emotional distress can contribute to the stimulations of the peripheral nervous system, which can develop into the perception of sensations and pain in the amputated section of the limb. 

Evaluating Symptoms

The diagnosis of this phantom limb phenomenon is primarily a diagnosis of exclusion and is greatly dependent on the patient’s history, hence laboratory tests are less required.  A complete blood count (CBC) can help rule out infection as the source of paraesthesia. An ultrasound can be ordered to look for neuromas as a possible pain stimulator. However, most importantly, a psychology evaluation may be indicative if the patient is having significant extrinsic triggers that may be contributing to the patient’s pain, which could signify the requirement of psychiatric therapy.

Treatment and Prognosis

Often, when phantom limb pain and sensations continue vigorously for more than six months, the prognosis for spontaneous improvement is poor: some patients will experience a lifelong struggle with chronic pain. Phantom limb is a very difficult and complex condition to treat, particularly due to the lack of understanding of the nature of the condition, and that the cause of the phenomenon varies between patients.

The first treatment is usually conservative and should include non-pharmacological and nonsurgical methods. Prosthetists should assess the stump – the site of amputation – and should encourage the patient to use a prosthetic device for improved mobility. Psychotherapists may help identify the psychological cause of the pain and sensations experienced by the patient with the aim to mitigate the experiences and to ease anxiety and depression. In the event that neither solution is successful, pharmacists will work to select appropriate pharmacological agents. The medication should be specific to the extent of pain and/or sensations, considering its debilitation and hindrance on everyday life, as well as the history of symptoms. The patient must be aware of why the medication is being administered and educated on the different pharmacological agents available and their effectiveness and adverse effects.

Treating phantom limbs tends to be for symptomatic control, and although no medications specifically for phantom limbs exist, some drugs designed to treat other conditions have been helpful in relieving nerve pain: 

  • Antidepressants, especially Tricyclic antidepressants, help relieve the pain of phantom limb phenomena. 
  • Receptor antagonist medications, specifically NMDA receptor antagonists, are anaesthetics which bind to specific receptors on nerve cells, blocking the binding of a protein called glutamate, which has a crucial role in relaying nerve signals.

Conclusion

Research about phantom limbs is still in early stages, hence currently nothing more can be done to prevent, reduce, and cure phantom limbs. With a variety of psychotherapy options, medication, and prosthetics, alongside occupational therapy, phantom limb pain and sensations can be relieved in some, but not all, cases. As mentioned before, there is no one treatment that works reliably or consistently in all patients; the outcomes for most patients are limited and the quality of life can be poor.

Swetha Babu, Youth Medical Journal 2021

References

BJA Education. (2016) 16(3): 107–112. Pain after amputation. https://doi.org/10.1093/bjaed/mkv028

Image 1: https://medicalxpress.com/news/2018-09-theory-phantom-limb-pain-effective. html

Hanya-Deutmeter, A., Cascella, A., Varacallo, A. (2021). Phantom Limb Pain. National Centre for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK448188/

Mayo Clinic, Mayo Foundation for Medical Education and Research. (2020, Oct. 29) Phantom Pain. https://www.mayoclinic.org/diseases-conditions/phantom-pain/diagnosis-treatment/drc-20376278

Cleveland Clinic. (2016, Mar. 14). Phantom Limb Pain. https://my.clevelandclinic.org/health/diseases/12092-phantom-limb-pain