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Health and Disease

Congenital Analgesia: The Condition Where You Cannot Feel Pain

While you may feel the rush of pain through your body when you stub your toe, the feeling is not felt at all to those with congenital insensitivity to pain. Congenital insensitivity to pain or congenital analgesia is an extremely rare condition when one is unable to experience physical pain. While this may seem beneficial to some, it is in reality quite detrimental, as those with CIP are unaware of any injuries that potentially could have occurred to them. This can potentially affect the life expectancy to those affected, as many health related issues and injuries can go undetected.

Congenital insensitivity to pain is caused by a mutation on the SCN9A gene, and is inherited as an autosomal recessive trait. SCN9A codes for the production of voltage gated sodium channels called Nav1.7s and when there is a mutation present, these channels are as a result affected.  Nav1.7 channels are on nerve cells, specifically on the ends of nociceptors or nerves that sense pain. When the mutation on the SCN9A gene occurs, these channels are affected, therefore affecting the individual’s ability to sense pain. 

People with congenital insensitivity to pain are able to distinguish whether something is sharp, or hot, however, they are unaware of any pain that is resulting due that specific stimulus. Due to this, people with CIP may experience bone fractures, burns, and underlying health issues. 

While there is no treatment for CIP, those affected are recommended to take annual X-rays and MRI’s, due to any possible injuries that could have occurred, as well as avoiding circumstances of self-injury. 

Congenital insensitivity to pain or congenital analgesia is a fascinating condition that affects very few individuals. Even though no treatment is available yet, many professionals in health care continue to research and bring more insight and understanding to this condition today. 

References

“Congenital Insensitivity to Pain.” Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, rarediseases.info.nih.gov/diseases/12267/congenital-insensitivity-to-pain.

“Congenital Insensitivity to Pain.” Wikipedia, Wikimedia Foundation, 20 June 2020, en.wikipedia.org/wiki/Congenital_insensitivity_to_pain.

“Life Without Pain .” :: Medical Discovery News :: http://www.medicaldiscoverynews.com/shows/260-pain.html.

“Nav1.7.” Wikipedia, Wikimedia Foundation, 16 Apr. 2020, en.wikipedia.org/wiki/Nav1.7.

“Treatment: Is There a Treatment(s) for Congenital Insensitivity to Pain?” ThinkGenetic, http://www.thinkgenetic.com/diseases/indifference-to-pain-congenital-autosomal-recessive/treatment/4530.

Bharathi Arivazhagan, Youth Medical Journal 2020

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Health and Disease

Thyroid Eye Disease: Symptoms, Diagnosis, and Treatment

Introduction

Thyroid eye disease, also known as Graves’ eye disease, is an autoimmune condition in which the eye muscles and fatty tissue behind the eye become inflamed. The main symptoms of thyroid eye are red, uncomfortable, and “bulging eyes.” These are caused by inflammation of the eyelid, tear glands, muscles, and fatty tissue behind the eye. Occasionally, this inflammation can lead to stiffness in the muscles, which can cause double, or blurred vision, as eyesight is not aligned between both eyes due to not being able to move parts of the muscle. Thyroid eye is an autoimmune disease caused by an immune attack on the tissue around the eye, irritating it and causing inflammation. 

Most people suffering from thyroid eye disorder (or TED) have Graves’ disease, which can detrimentally affect the thyroid gland, usually causing hyperthyroidism (overactive thyroid). 25% of those with Graves’ disease will also develop TED sometime before or during treatment.  Those suffering from Graves’ disease will double their chances of developing TED by smoking. A person diagnosed with thyroid eye will likely be placed under the care of an endocrinologist (a doctor specializing in hormonal diseases) as well as an ophthalmologist (an eye doctor). These departments will be the first port of call during treatment and should be informed if symptoms worsen.

Symptoms and Diagnosis

One major issue associated with TED is how difficult it is to diagnose. Thyroid eye is usually mistaken for symptoms associated with hayfever, conjunctivitis, or allergies. There are signs that directly point to TED and not the aforementioned conditions: continuing symptoms all year around with no improvement in winter months, no stickiness around the eye, and no improvement of symptoms after trialling different allergy solutions. 

In order to reduce symptoms of thyroid eye, it is imperative the sufferer attempts to quit smoking, if they are in the habit. Furthermore, it is important that they listen to their doctor’s advice and are aware of their changing thyroid levels, as well as monitoring them and following medical advice (e.g. attending blood tests every six months). This can sometimes help to alleviate symptoms and reduce the chance of TED becoming more severe.

It is vital to recognize that TED massively impacts individuals’ lives. From self confidence, to eyesight, thyroid eye can affect your daily life. Many sufferers struggle with low self esteem and self consciousness due to their eyes having a “bulging” appearance. Double vision can also be frustrating, meaning those with thyroid eye can experience confusion, especially when reading or trying to understand someone’s facial expression. This can be taxing on the patient, as well as family and friends, so it is crucial that everyone researches how they can support their loved one. Charities such as the “Thyroid Eye Disease Charitable Trust” and the “British Thyroid Foundation” can offer support and advice to help patients come to terms with the condition and adapt their daily life for ease. 

Treatment

There are a range of different treatments to help with some painful symptoms of TED. Artificial tears can be used to reduce the feeling of “grit in the eye” that can be associated with thyroid eye disease. If inflammation is severe, a doctor may prescribe an oral steroid to reduce it, or administer steroids intravenously. Some patients also find that having prisms attached to glasses can reduce their double vision. There are also surgical options to fix double vision, protect the eyelids, create space in order to allow the eye to close better, and protect the eyeball. 

The best thing a family member can do for a loved one suffering from TED is support and listen to them. Any disease affecting eyesight can be extremely unnerving for the sufferer, as their independence decreases, they may have to become more reliant on those around them. Especially for adults, double vision can be frustrating as it makes day to day activities harder. Teenagers and young people may feel self-conscious about their appearances and the possibility of having to wear an eye patch to alleviate vision problems. A caretaker, friend, or relative, should offer help, but make sure to give them space and allow their loved one to attempt things independently. They should be careful not to sound condescending, be supportive, and if they are comfortable discussing it, talk to them about the condition and their emotions surrounding it. Before forcing their help upon someone, those close to a person with thyroid eye should communicate with them and ask what they would like you to do.

References

Douglas, Raymond S. “Thyroid Eye Disease (TED or Graves Eye Disease).” Thyroid Eye Disease (TED or Graves Eye Disease) | Kellogg Eye Center | Michigan Medicine, http://www.umkelloggeye.org/conditions-treatments/thyroid-eye-disease.

“Graves’ Eye Disease.” American Thyroid Association, http://www.thyroid.org/graves-eye-disease/.

MacEwen, Caroline. “Expert Opinion – Diagnosing Thyroid Eye Disease.” GP, GP, 14 Mar. 2012, http://www.gponline.com/expert-opinion-diagnosing-thyroid-eye-disease/ophthalmology/article/1120742.

“Thyroid Eye Disease.” British Thyroid Foundation, 2019, http://www.btf-thyroid.org/thyroid-eye-disease-leaflet.

“Thyroid Eye Disease.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/17558-thyroid-eye-disease. 

Sophie Farr, Youth Medical Journal 2020

Categories
Health and Disease

Lung Cancer: When Your Own Lungs Betray You

Your lungs are really amazing. An anatomy professor explains why

Introduction

When lung cells are frequently exposed to a carcinogen (cancer-causing factor), the cells’ DNA and metabolic processes may be damaged; as a result, creating abnormal cells within the organs. These cells do not function properly like normal cells. They also multiply at a faster rate than normal cells and form tumors, or clumps of cancerous cells, inside the lungs. Cancerous tumor cells will start demolishing healthy cells near it. Ultimately, it will start metastasizing or spreading to organs near the lungs, like the bones, adrenal glands, liver, kidneys, and even the brain. This will be adverse to the body’s metabolism since these cancer cells do not aid the lungs like normal, healthy cells and can cause death. There are two types of lung cancer, small cells (the more aggressive type) and non-small cells. The majority of lung cancer cases are non-small cell lung cancer (84%). As for 2020, the American Cancer Society estimated that there are approximately 228,820 new cases of lung cancer and 135,720 deaths from lung cancer. About 1 in 17 women and 1 in 15 men will get lung cancer in their life, both smokers and non-smokers, although smokers will have a higher chance of having lung cancer. Its survival rate is measured in a relative survival rate method: 5-year relative rate by the American Cancer Society. It compares patients with identical stages and types of cancer to the rest of the population. For instance, people with localized lung cancer have a 5-year relative survival rate of 61%. This means that the people who have this type of cancer usually are about 61% more likely to live 5 years longer than those who don’t have this type of lung cancer. ACS also uses the SEER (Surveillance, Epidemiology, and End Result) database, which divides lung cancer into three stages: localize (the cancerous cells still resides within the lungs), regional (cancer had spread to neighboring structures from the lung), and distant (cancer metastasized to other organs). This chart is from the American Cancer Society that shows 5-year relative survival rate for non-small cell lung cancer from 2009 to 2015:

SEER stage5-year relative survival rate
Localized61%
Regional35%
Distant6%
All stages combined24%

This chart from American Cancer Society shows the 5-year relative survival rate for small-cell lung cancer between 2009-2015:

SEER stage5-year relative survival rate
Localized27%
Regional16%
Distant3%
All stages combined6%

Keep in mind that these numbers show an overall statistic; patients may have a better or worse chance of survival, for there are other personal factors that contribute. These numbers also only apply to the first time a patient is diagnosed.

Causes 

Tobacco is the most common cause of lung cancer. It is also a highly significant risk factor for lung cancer. As many as 80-90% of patients diagnosed are smokers or former smokers. The carcinogens in tobacco products can cause and hasten the process of lung cancer. It can further make your lungs more affected by hazardous chemicals such as radon and asbestos. Those who are exposed to smokes from these tobacco products (secondhand smoking) can be at risk of lung cancer. Adding on, if a smoker can quit smoking, the chances of getting lung cancer significantly reduces, although never diminishes. Therefore, it is always optimal to quit smoking. 

Another risk factor of lung cancer is carcinogens. These are chemicals that, when consumed, can have the ability to cause cancer. Radon, asbestos, tar, arsenic, thorium, chromium, nickel, soot, are all carcinogens, just to name a few. The longer a person is exposed to these carcinogens, the higher the risk for lung cancer. These carcinogens can also be carried in the air (if polluted). Cooking with kerosene fuels, biomass, etc. can also contribute to lung cancer. 

People of 65 and older are also at higher risk for lung cancer. Also, people with a history of lung diseases (like COPD and pulmonary fibrosis) may also be at a higher risk of getting this kind of cancer. Adding on to the last point, the people with a family history (immediate members) suffering from lung cancer are also at higher risk of getting the disease. This can be passed down through genetic mutation (extremely rare) or by being exposed to the same environmental risk factors (such as smoke from tobacco products and carcinogens). 

Radiation therapy can contribute to the chances of getting lung cancer. People being treated for breast cancer and Hodgkin lymphoma. Although the current medical advances that can minimize this risk factor, it is still a concerning aspect not to be overlooked. 

Diet can also affect the likelihood of getting lung cancer. Unsafe water sources that contain arsenic can cause damage to the lungs and potentially cause lung cancer. People who take many beta-carotene pills over the year can increase their likelihood of getting lung cancer. However, foods that contain beta-carotene are considered safe.

Please keep in mind that all these factors have the CHANCE of causing cancer. Other factors such as the amount of time a person is exposed to these risk factors may determine if they will get cancer or not. Getting exposed to charcoal’s smoke will not give you cancer immediately. The dose is the poison. 

Lung Cancer Risk Factors Infographic

Symptoms and Diagnosis

Before reading on, please keep in mind that this article is not meant for medical advice or diagnosis. Please consult your physician if you suspect you have cancer or any other medical issues.

Symptoms of lung cancer don’t usually manifest until the later stages of this disease. However, in many cases, these symptoms do manifest early on; as a result, the patient will have a higher chance of survival. Symptoms of lung cancer can be confused with other lung diseases and disorders. Therefore, it is important to consult your physician if you are concerned that the symptoms listed below may signal lung cancer. Several symptoms of lung cancer includes:

  • Constant and worsening coughs
  • Blood or sputum-coughing
  • Hoarseness
  • Constant chest pain that gets more painful when performing activities that involves the lung (laughing, coughing, deep breathing, etc.)
  • Shortness of breath
  • Lung infections such as bronchitis and pneumonia occur oftenly
  • Wheezing 

Some symptoms that manifest when the cancer spreads to other organs:

  • Bone pain
  • Swelling of the lymph nodes
  • Seizures, headaches, dizziness, and other nervous system-related symptoms
  • Jaundice (when the skin and eyes turn yellow)
  • Blood clots

Doctors choses diagnosis based on factors like a patient’s medical history, symptoms, and physical exam results. As for the USC lung cancer screening program, patients must meet these criteria, as quoted from their website linked below:

  • “You must be at least 55 years old; have smoked the equivalent of one pack of cigarettes a day for 30 years; and be either a current smoker or have quit within the past 15 years
  • You must be older than 50; have smoked the equivalent of one pack of cigarettes a day for 20 years; and have at least one of the following risk factors:
    • Significant chronic lung disease (chronic obstructive pulmonary disease [COPD], pulmonary fibrosis)
    • Exposure to toxins such as radon, asbestos, coal and diesel fumes
    • A first-degree relative with lung cancer
    • A personal history of lung cancer, lymphoma or head and neck cancer”

Doctors may perform an imaging test on you for cancer signs. This means taking pictures of parts that are inside your body. One method that your doctor may use is CT scanning. CT scanning uses the typical donut-like machine with a table that pierces through the hole that you see in medical movies. It is an X-ray machine that takes several pictures of different parts of your body as you slide through the machine. Another method is PET scanning. This method is where the patient ingest a radioactive sugar that when a special camera takes pictures, the pictures show whether the cancer has metastasized to other organs or lymph nodes or not. Furthermore, bone scanning is where your doctor injects a safe amount of radioactive material in your veins. This substance would then gather up in the abnormal region of your bone and express themselves as a dense, gray to black shade, which can be cancerous. There are many other kinds of imaging methods out there. 

Procedures that your doctor may perform includes but not limited to:

  • Sputum cytology (where your doctor takes the phlegm, sputum or mucus from the lung to inspect them for cancer cells.)
  • Bronchoscopy biopsy (your doctor inserts a long and flexible tube down to your airways in order to remove a sample from the region for inspection.)
  • Endobronchial ultrasound (your doctor inserts a tube down your airways with ultrasound attached to it in order to look at nearby tissues, organs, and lymph nodes. Needles will pass through the bronchoscopy to get the biopsy sample. The patient will be numbed and will be under light sedation.)
  • Thoracentesis (due to cancer, or some other medical conditions, your back may be filled with liquid. Your doctor will use a needle and inject it in the between your ribs to drain the fluids. The fluid then will be inspected for cancer cells.)
  • And so on…

If you suspect that you have cancer, please consult your doctor and discuss your concern.

Surprising Lung Cancer Symptoms

Treatment

When doctors have enough evidence to diagnose you with cancer, you will begin treatment. The most common three methods are surgery, chemotherapy, and radiation therapy. For small cell lung cancer, chemotherapy and radiation is more common. Another treatment method is targeted therapy. It is a subcategory of chemotherapy. However, unlike general chemotherapy, where the drug will eliminate all kinds of cells, healthy or cancerous, targeted therapy only attacks cancer cells. A new and emerging cancer treatment is immunotherapy. This means that doctors train your immune system to fight against cancer. Three types of immunotherapy includes: CAR T Cells (Chimeric Antigen Receptor T cells), where scientists generate a special kind of antigen receptors on the patient’s T-cells so they can easily bind to the cancer cell’s antigens and eliminate them. Another immunotherapy treatment is cancer vaccination. This is quite self-explanatory. The doctor injects harmless cancer cells into your body to prepare your body for defense when the real cancer hits. Thirdly, checkpoint inhibitors are basically drugs that disable the proteins that prevent your body from fighting cancer. Complementary and Alternative Medicine can go along with standard treatment. These include acupuncture, meditation, magnet therapy, herbal teas, and so on. These are only several treatment methods. Check with your physician for the most fitting treatment for you. 

Lung Cancer Symptoms, Causes, Treatments, Surgeries, and more

Conclusion

Overall, lung cancer is when your lung cells mutate and don’t function properly; it gets in the way of your normal organ functions. It can be divided into non-small cell lung cancer and small cell lung cancer. The three stages of cancer are localized, regional, and distant. Some causes of cancer include tobacco, exposition to carcinogens, family history of lung cancer, old age, etc. When lung cancer manifests in symptoms, these symptoms include constant and worsening cough, blood-coughing, wheezing, jaundice, bone pain, swelling of lymph nodes, etc. Your doctor can diagnose you through CT scans, PET scans, bronchoscopy biopsy, thoracentesis, and so on. When you are diagnosed with lung cancer, a team of doctors may treat you with surgery, chemotherapy, immunotherapy, radiation, and so on.

References

Cancer Treatments. (n.d.). Memorial Sloan Kettering Cancer Center. Retrieved August 15, 2020, from https://www.mskcc.org/cancer-care/diagnosis-treatment/cancer-treatments

Cancer-Causing Substances in the Environment. (2018, December 28). National Cancer Institute. https://www.cancer.gov/about-cancer/causes-prevention/risk/substances

Division of Cancer Prevention and Control, Centers for Disease Control and Prevention. (2019, September 18). How Is Lung Cancer Diagnosed and Treated? | CDC. Centers for Disease Control and Prevention. https://www.cdc.gov/cancer/lung/basic_info/diagnosis_treatment.htm#:%7E:text=it%20has%20spread.-,People%20with%20non%2Dsmall%20cell%20lung%20cancer%20can%20be%20treated,doctors%20cut%20out%20cancer%20tissue

Harvard Health Publishing. (2017, February). Lung Cancer Overview. Harvard Health. https://www.health.harvard.edu/a_to_z/lung-cancer-overview-a-to-z

How Is Lung Cancer Diagnosed? (2018, November 19). American Lung Association. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/learn-about-lung-cancer/how-is-lung-cancer-diagnosed

Jett, MD, J. R. J. (2012, October). Lung Cancer Risk Factors. National Jewish Health. https://www.nationaljewish.org/conditions/health-information/health-infographics/lung-cancer-risk-factors

Lung Cancer Signs & Symptoms | Common Symptoms of Lung Cancer. (2019, October 1). American Cancer Society. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/signs-symptoms.html

Lung Cancer Statistics | How Common is Lung Cancer. (2020, January 8). American Cancer Society. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html#:%7E:text=The%20American%20Cancer%20Society’s%20estimates,men%20and%2063%2C220%20in%20women)

Lung Cancer Symptoms. (2020, May 28). American Lung Association. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/learn-about-lung-cancer/symptoms

M. (2020, February 25). Expert diagnosis. USC Norris Comprehensive Cancer Center. https://cancer.keckmedicine.org/patients/cancer-programs/lung-cancer/lung-screening-and-diagnostic-imaging/?gclid=CjwKCAjwkJj6BRA-EiwA0ZVPVgPHrzdOio9kG_JST2rDNOO2BzofViLnlEPqccNdSaZvpikOWuYgLBoCYqEQAvD_BwE

https://www.nationaljewish.org/conditions/health-information/health-infographics/lung-cancer-risk-factors

Reducing Your Risk. (2019, June 24). LUNGevity Foundation. https://lungevity.org/for-patients-caregivers/lung-cancer-101/reducing-your-risk

Ratini, DO, MS, M. R. (2020, April 17). Slideshow: Surprising Signs You Might Have Lung Cancer. WebMD. https://www.webmd.com/lung-cancer/ss/slideshow-lung-cancer-surprising-signs

Andrew Pham, Youth Medical Journal 2020

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Health and Disease

State-Mandated Childhood Vaccinations

Introduction

Vaccines, a type of substance discovered in 1796, have been the center of conversations between frustrated politicians, overly-concerned mothers, and curious students themselves. This paramount medical discovery that regulates and regards the well-being and health of children all over the United States is now in the hands of our government. Their main point of discussion: the mandate of childhood vaccinations by state.

Background

 The concept of vaccinating resulted from a smallpox outbreak in England in 1796. British Dr. Edward Jenner realized he had the ability to protect a non-immunized child from the deadly smallpox virus by injecting the child with lymph from a cowpox blister. The live cowpox virus would act as a weaker, asymptomatic form of the smallpox virus, safely allowing the body’s immune system to be prepared for the fatal smallpox virus. However, Edward Jenner’s methods and theories of vaccination were constantly looked down upon. At the time, the local clergy in Jenner’s town believed that the smallpox vaccine went against common Christian morals as it involved the flesh of an animal being injected into a human body. In Great Britain, the Anti-Vaccination League formed soon after, publishing numerous anti-vaccination journals that promoted self-liberty and Christian values. When the concept of vaccines was starting to be implemented by doctors in the United States, it was met with opposition. Magazines, which were critical to the imposition of liberty that modern vaccinations brought, started to become popular. Following suit of European countries, the anti-vaccination movement in the U.S. began to grow in the mid to late 1900s. This mainly resulted from a pattern of newly developed vaccines, such as the Diphtheria, Pertussis, and Tetanus (DPT) vaccine; the Polio vaccine; and the Measles, Mumps, and Rubella (MMR) vaccine. About 15 years later, after the skeptical DPT: Vaccine Roulette documentary aired on television, Physician Andrew Wakefield published a paper in the reputable medical journal, The Lancet, claiming a correlation between the MMR vaccine and autism. The article was eventually retracted, however, and Wakefield’s medical license was revoked. Nevertheless, the article sparked many more doubts amongst parents on the safety of vaccines in general and muddled the assurance parents would receive from their pediatrician. It additionally sparked the national debate on the mandate of vaccinations that many are still engrossed in today.  

Eradication of Diseases

One of the primary effects of vaccines is that they assist in eradicating the most fatal and contagious diseases by promoting mass injection. In 1921, there was a presence of over “150,000-260,000 cases of pertussis” (Vidula). These cases dramatically dropped following the distribution of the Pertussis vaccine, as recent reports indicated there would be “97.56% fewer pertussis cases in the United States” than there would be without mass immunization (Vidula). The high percentage of vaccine coverage in children 19 – 35 months old resulted in a 95.4% decrease in the annual morbidity of children diagnosed with Pertussis when comparing figures from the 20th century to the 2000s. It is safe to assume that mandatory vaccinations will promote these trends to occur continuously, as more individuals will take the particular vaccine, reducing the number of cases annually. These statistics can also be explored with the Diphtheria vaccine. Before the diphtheria vaccine was developed in the 1930s, “the disease infected about 21,000 people in the United States each year” with a death toll of nearly “1800 people” (Welch). Less than 80 years after the introduction of the vaccine, “by 2006, both numbers [of cases and deaths] were zero” (Welch). In both statistics presented, the death toll and injury resulting from these vaccine-preventable diseases were extremely large before the introduction of a vaccine. However, it is evident that when accessible and clinically tested vaccinations were immunizing a colossal number of people safely, such as the numbers in 1921, the numbers were not repeatedly occurring. Suppose these trends of mass immunization were to continue in the future. In that case, such vaccine-preventable diseases could be completely eradicated in the United States, similar to the lifetime of the Poliovirus and the Smallpox virus in the nation. 

Economic Effects

Furthermore, the occurrence of cases from vaccine-preventable diseases is reported to spur financial issues for both parents and medical institutions. For instance, in a 2005 measles outbreak in Indiana, “thirty-four individuals in total contracted measles” with an additional 500 cases discovered as contacts of the original thirty-four (Andrada). This outbreak ultimately cost “health establishments an estimated $167,685 ($4,932 per confirmed case)” as ninety-nine hospital personnel were assigned to deal with the cases. Additionally, more than 3,500 person-hours were spent on “telephone calls, MMR vaccines, immunoglobulin, specimen collection kits and laboratory tests, and transportation” (Andrada). The data gathered from this small Indiana measles outbreak conveys the general amount of funds utilized to manage cases of diseases where protection is readily available. Instead of hospital funds being directed towards clinical trials involving novel illnesses and developing new research, funds were being spent on managing preventable diseases, ultimately lengthening the time needed by institutions to obtain new research about diseases that aren’t vaccine-preventable yet. Parents and sick individuals face a financial burden as well when confronted by a fatal, yet preventable disease. To identify this economic burden, the National Center for Biotechnology Information conducted a study in which “107 individuals of 216 subjects with identified cases of Pertussis completed questionnaires” and had medical records reviewed to determine the total costs of the illness, “including physician office visit … hospitalization…  additional child care, and lost days from school or from work” (Pichichero and Treanor). The results of this study indicated that the total “cost” of the disease was $381,052. Moreover, the impact of the disease primarily affected the parents who took care of their ill children. “Child care costs ranged from $12 to $2688,” and for every 50 families, one adult lost workdays to “provide child care for an average of 8.3 days,” which is a loss in income for almost two working weeks (Pichichero and Treanor). In one particular case, “2 adults lost an average of 44 days from work,” resulting in over a month of reduced income (Pichichero and Treanor). It is evident that once epidemics advance, unemployment will occur, and most parents who prioritize their child’s well-being before their living will automatically prohibit themselves from contributing to the state’s economy. 

Psychological Effects of Quarantine

Additionally, once a community has been inflicted by a vaccine-preventable disease, one of the only methods present to prevent the disease’s continuation would be to quarantine, a method proven to be connected to mental disorders. The University of Toronto surveyed 129 individuals who had been quarantined during the SARS outbreak. The survey utilized psychometric tests designed to identify the signs of depression and PTSD. It was noted that the 129 individuals exhibited “a high prevalence of psychological distress” and that “symptoms of posttraumatic stress disorder and depression were observed in 28.9% and 31.2% of respondents” (Galea and Hawryluck). These results indicate the high likeliness of receiving mental distress after being quarantined, a method that could easily be prevented by mandatory vaccinations. Mandatory vaccinations would dramatically reduce the probability of an epidemic occurring within a community needing a quarantine. Another study was conducted by the National Center for Biotechnology. It analyzed the psychological effects of quarantine on a sample population in Sierra Leone, an area that had recently experienced an Ebola quarantine. The results of this study convey that the “prevalence of any anxiety-depression symptom was 48%” of the sampled and “[prevalence] of any PTSD symptom 76%” (Jalloh et al.). Additionally, “6% met the clinical cut-off for anxiety-depression” and “ 27% met levels of clinical concern for PTSD” (Jalloh et al.). It was concluded that the longer one spends quarantined, the higher the chance that they have a resulting mental disorder. Whether vaccine access is restricted unwillingly, meaning it hasn’t been developed yet, such as an Ebola vaccine, or willingly, such as a Polio vaccine, an individual has a higher chance of contracting the virus and therefore being quarantined in their state. Advocates of the mandate on routine vaccinations, therefore, argue that laws have abilities to prevent masses of people from being quarantined and receiving the subsequent mental health effects that could impact them throughout their lives. 

Immunity in Future Generations

Most importantly, many argue that mandatory vaccinations have the ability to benefit the United States for years to come, as they directly protect future generations. Before 1963, when the Measles vaccine was commercialized and distributed, there was an annual amount of 500,000 measles cases reported, where the highest incidence of measles “was among 5–9-year-olds” who accounted for “more than 50% of reported cases” (“Measles”). However, after the introduction of the vaccine in 1963, a “median of only 29%” of the cases amongst children of all ages from 1980 to 1988 reported were “among children younger than 5 years of age” (“Measles”). According to the national vaccination schedule that many pediatric offices use, most children only receive their complete dosage of the measles vaccine at age 6, some even later. Therefore, the statistics that resulted in the 1980s convey that most children who couldn’t yet receive the measles vaccination due to their age still didn’t contract it, opposite to the trend in previous decades. This is due to the fact that every single child utilizes their parents’ immunization and depends on it for the health of their neonatal immune system. The young children in the 1980s had parents who grew up in the 60s, a time when the Measles vaccine was being produced and administered in heavy amounts; therefore, it is safe to assume that their parents’ generation received the vaccine, automatically improving the immunity of the generation immediately after them. This improvement in immunity was shown in the statistics from 1980 and can be further demonstrated in statistics of the 21st century. Furthermore, the National Center for Biotechnological Information states that a breast-fed infant is provided with “0.25-0.5 grams per day of secretory IgA antibodies via the milk” (Hanson and Soderstrom). The number of grams of the secretory antibodies, crucial proteins for the functions of the immune system, can be altered due to the immunization of the mother, as “recent studies suggest that it may be possible by vaccination” of the mom to “increase the immunity [of]… the breast-fed infant via the milk secretory IgA antibodies” (Hanson and Soderstrom). This further emphasizes the amount of protection vaccination provides for the future children of the individual taking the vaccine, which advocates say can be promoted and regulated through mandatory state vaccination laws.

The View of Most Opponents

Many opponents of mandatory vaccinations believe that the MMR vaccine and other common vaccines that provide three doses of different substances within one shot can cause permanent brain damage and autism. Consequently, they believe that the state shouldn’t mandate it because of the varying effects it has on a variety of people. Concerns were rising amongst the residents of Japan, as they too feared that the MMR vaccine would cause an adverse reaction relating to aseptic meningitis since three doses of different vaccines were administered simultaneously. As a result, in Japan, “in 1993, the combination MMR vaccine was discontinued,” and the vaccination was instead “replaced with separate measles, mumps, and rubella vaccines” (Ching and Kuwabara). However, after the change, there were no resulting differences in the number of brain disorders developed in children after the new vaccination schedule had been administered. Nevertheless, there was still heightened fear amongst the public about the MMR vaccine’s effects on the brain. It can be concluded that many of these fears originated from a research paper published in a reputable medical journal, The Lancet. This paper, published in 1998, describes a correlation between the administration of the MMR vaccine and autism. However, the piece was completely retracted from the journal in February 2010, with a statement from the medical community involved with the paper, admitting “that several elements in the paper were incorrect” and “contrary to the findings of the earlier investigation[s]” on the MMR, prior to the analysis done by Wakefield (Andrade and Sathyanarayanana Rao). Additionally, Dr. Andrew Wakefield “[was] held guilty of ethical violations” as there was strong evidence that his team had conducted “invasive” investigations on the test subjects without obtaining “ethical clearances” or formal consent (Andrade and Sathyanarayanana Rao). Therefore, this conveys that, despite the investigations providing evidence that the MMR vaccine had the potential to cause brain damage, the tests done to support such a claim were faulty and weren’t credible, ultimately meaning that the claim itself wasn’t accurate. Moreover, it concludes that the reason behind the objection of state-mandated childhood vaccination is not and can never be well supported.

Conclusion

Due to the points mentioned above, it is reasonable to conclude that state-mandated childhood vaccinations will provide a more stable state health-wise and financially. Therefore, the vaccinations should be enforced by law because of their ability in protecting future generations, eradicating dangerous and lethal diseases that have had a historical impact, providing a more stable budget for both health institutions and individuals who are in charge of caring for the ill, and directly preventing the damaging emotional effects of quarantines. The varying information on both sides of the debate surrounding a state mandate is extremely important as it has created a large amount of panic amongst parents who are hearing a variety of contradicting opinions, yet are focused on providing the best health for their child. The effect of this particular debate is common with almost all controversial issues, as both sides will usually have the same ultimate goal, yet argue about the most ideal way to approach it. Therefore, the different opinions can be a source of panic, as people who are merely trying to get more insight into the topic will be flabbergasted by the amount of contradicting ideas. However, once more insight is gained on state-mandated vaccinations, including the economic and social benefits, and the assurance it provides individuals and parents, there will be a more apparent consensus on the vaccine issue. 

References

Andrada, Carolina. “Cost of Outbreak Response.” Outbreak ObservatoryI, Johns Hopkins Center for Health Security, 12 July 2018, https://www.outbreakobservatory.org/outbreakthursday-1/7/12/2018/cost-of-outbreak-response. Accessed 4 March 2020.

Andrade, Chittarajan, and T.S Sathyanarayanana Rao. “The MMR vaccine and autism: Sensation, Refutation, Retraction, and Fraud.” Indian Journal of Psychiatry, National Center for Biotechnology Information, 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136032/. Accessed 4 March 2020.

Ching, Micheal, and Norimitsu Kuwabara. “A Review of Factors Affecting Vaccine Preventable Disease in Japan.” Hawai’i Journal of Medicine & Public Health : A Journal of Asia Pacific Medicine & Public Health, National Center for Biotechnology Information, 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300546/. Accessed 5 March 2020.

Hanson, LA and T. Soderstrom. “Human Milk: Defense Against Infection.”  Progress in Clinical and Biological Research, National Center for Biotechnology Information, 1981, https://www.ncbi.nlm.nih.gov/pubmed/6798576. Accessed 9 March 2020.

Hawryluck, Laura, et al. “SARS Control and Psychological Effects of Quarantine, Toronto Canada.” Emerging Infectious Diseases, National Center for Biotechnology Information, 2004,  /www.ncbi.nlm.nih.gov/pmc/articles/PMC3323345/. Accessed 9 March 2020.

Jalloh, MF, et al. “Impact of Ebola experiences and risk perceptions on mental health in Sierra Leone.” BMJ Global Health, National Center for Biotechnology Information, 2018. https://www.ncbi.nlm.nih.gov/pubmed/29607096. Accessed 9 March 2020.

“Measles.” Epidemiology and Prevention of Vaccine-Preventable Diseases, Centers for Disease Control and Prevention, 2019, https://www.cdc.gov/vaccines/pubs/pinkbook/meas.html. Accessed 5 March 2020.

Pichichero, ME and J Treanor. “Economic Impact of Pertussis.” Archives of Pediatrics & Adolescent Medicine, National Center for Biotechnology Information, 1997, https://www.ncbi.nlm.nih.gov/pubmed/9006526. Accessed 9 March 2020.

Schafly, Andrew. “The Chickenpox Vaccine Is Unnecessary and Its Safety Is Unproven.” Vaccines, edited by Sylvia Engdahl, Greenhaven Press, 2009. Current Controversies. Gale In Context: Opposing Viewpoints, Accessed 14 Feb. 2020.

Staver, Mathew D. “Mandatory Vaccinations Threaten Religious Freedom.” Should Vaccinations be Mandatory?, edited by Noël Merino, Greenhaven Press, 2010. At Issue. Gale In Context: Opposing Viewpoints. Accessed 14 Feb. 2020.

Vidula, Mahesh. “Individual Rights vs. Public Health: The Vaccination Debate.” Angles / Individual Rights vs. Public Health: The Vaccination Debate. Angles, 2010. http://web.mit.edu/angles/2010_Mahesh_Vidula.html Accessed 14 February 2020.

Welch, Matt. “Should Vaccines Be Mandatory?” Reason, 2014. Sirsissuesresearcher, Accessed 9 Mar. 2020.

Prish Ramnath, Youth Medical Journal 2020

Categories
Health and Disease

Tay-Sachs Disease: The Rare Genetic Disorder

Introduction

Tay-Sachs disease is a very rare disorder that destroys nerve cells in the brain. It is found in infants who don’t have enough of an enzyme, known as beta-hexosaminidase. 15 (HEX-A) is a defective gene that prevents the body from making this protein.  The beta-hexosaminidase plays a very important role in the brain as well as the spinal cord. Not having enough of this enzyme can cause this disease to be very severe and can be extremely dangerous.  Tay-Sachs is usually found amongst infants who are typically from the ages 3-6 months old and symptoms usually progress from then on out. There are 3 types of  Tay-Sachs disease: infantile, juvenile, and late-onset/adult. However, the most common type is infantile which can start to appear in only the first few months. As the infant continues to grow, Tay-Sachs will start affecting the baby’s sight, hearing, and movement. Progressions usually happen very quickly and by the age of 2, the child will be completely disabled or have seizures. Children with Tay Sachs don’t live a long life and typically pass away by the age of 5.

Symptoms

Symptoms of Tay Sachs disease include muscle weakness which can also lead to paralysis. The infant may also be startled by sound, which will also start to progress into deafness. Further on, the child may start to see red spots, known as cherry-red spots of the macula, that develop in the back of the child’s eyes. This will start to progress into blindness and they will start to be unresponsive and have delayed mental and social development. If a child is having any problems with seeing, hearing, or moving the child must get tested to see if they have Tay-Sachs. However, Tay-Sachs is a very rare disease (less than 20,000 cases per year) so the chances of a child having it are extremely low. Another symptom of Tay-Sachs would be developmental regression. This means that the infant will most likely lose many developmental milestones, causing the infant to slowly regress physically and also mentally, such as difficulty in speaking and swallowing.

Inheritance

Tay-Sachs is inherited from an autosomal recessive pattern. Autosomal recessive is an inheritance pattern that both copies of the gene in each cell have this mutation. This means that if both parents are a carrier for a disease it is very likely that their child will also be a carrier or have the disease. However, autosomal recessive disorders aren’t usually seen in every generation of a family that is affected. If one of the parents is in fact a carrier for Tay-Sachs, then it is possible that the child will also inherit this mutation. There is a 1 in 4 chance that the child will have the disease, a 1 in 2 chance to be an unaffected carrier like each parent, or there’s a 1 in 4 chance that the child would be unaffected and not a carrier.

Risk

Tay-Sachs is commonly found in people with a certain ancestry, but most commonly found in people who identify as Ashkenazi Jews. Ashkenazi Jews are people who have families that are from the Jewish community that originates from Eastern Europe. Most Ashkenazi Jews are more likely to have autosomal genetic disorders like Tay Sachs but most of them can be preventable. For Tay-Sachs however, there is a 1 in 25 carrier frequency for Ashkenazi Jews. Tay-Sachs is also starting to be found in the Irish American community as well. There is an estimate that 1 in 50 Irish and Irish Americans are carriers for the Tay-Sachs disease.

Diagnosis

Tay-Sachs can be diagnosed by prenatal tests like chorionic villus sampling. It is important for healthcare professionals to look at the person’s medical history as well. The diagnosis will include a blood test that detects whether or not the child has high or low beta-hexosaminidase. This will tell us whether or not the mutation is present or not. However, Tay-Sachs can be detected before birth if parents decide to take a blood test to see if they are a carrier. 

Conclusion

Although there is currently no cure for Tay-Sachs, it is important to take a blood test to see if you are a carrier for any genetic diseases that can be caused by autosomal recessive patterns. Tay-Sachs disease isn’t a very common genetic disease. However, if your family does identify as Ashkenazi Jews, it is recommended that you take blood tests to see if you are a carrier for other genetic disorders like Tay-Sachs. There are treatments for Tay-Sachs but this is only to keep the child comfortable. For example, medicine for pain or anti-epileptics to control seizures. If you have more concerns about being a possible Tay-Sachs carrier, it is important to contact a doctor or healthcare professional.

References

Reference, G., 2020. Tay-Sachs Disease. [online] Genetics Home Reference. Available at: <https://ghr.nlm.nih.gov/condition/tay-sachs-disease#inheritance&gt; [Accessed 25 August 2020].

“HEXA Gene – Genetics Home Reference – NIH.” U.S. National Library of Medicine, National Institutes of Health, 2020, ghr.nlm.nih.gov/gene/HEXA.

“Tay-Sachs Disease.” Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, 23 Jan. 2018, rarediseases.info.nih.gov/diseases/7737/tay-sachs-disease.

Herndon, Jaime. “Tay Sachs Disease:Treatments, Symptoms, Risks and More.” Healthline, Healthline Media, 25 July 2012, http://www.healthline.com/health/tay-sachs-disease.

“Tay-Sachs Disease (for Parents) – Nemours KidsHealth.” Edited by Rupal Christine Gupta, KidsHealth, The Nemours Foundation, Oct. 2014, kidshealth.org/en/parents/tay-sachs.html.

Egan, Casey. “Irish Americans Warned about Tay-Sachs Disease Striking Community.” IrishCentral.com, 7 Sept. 2016, www.irishcentral.com/culture/education/irish-americans-warned-about-tay-sachs-disease-striking-community.

“Preventable Jewish Genetic Diseases.” 19 Jewish Genetic Diseases | Nicklaus Children’s Hospital, http://www.nicklauschildrens.org/medical-services/personalized-medicine-(pmi)/the-victor-center/19-preventable-jewish-genetic-diseases.

Mary Mai, Youth Medical Journal 2020

Categories
Health and Disease

What is ADHD?

A person with ADHD experiences a multitude of impairments, as well as problems with maintaining attention or completing a selected task. Some people with ADHD may have issues with sitting still and other symptoms. Whereas anyone might struggle with listening to things they find disinteresting from time to time, those with ADHD face consistent challenges with maintaining attention, and will be quick to follow through on impulses or become distracted. An individual with ADHD experiences impulsivity and severe distraction that is atypical for that person’s age. Signs of ADHD are typically clear throughout childhood, and parents quickly take notice of them.

Attention deficit/hyperactivity disorder (ADHD) might have an effect on all aspects of a child’s life. Indeed, it impacts not only the kid, but also the parents and siblings, inflicting disturbances onto family and matrimonial functioning. The adverse effects of ADHD faced by children and their families change throughout the years of educational institution, with varied aspects of the disorder being additionally distinguished at different stages. ADHD might persist into adulthood, inflicting disruptions onto their work and private life.

Attention deficit/hyperactivity disorder (ADHD) is a chronic, enervating disorder that can impact several aspects of an individual’s life and cause educational difficulties. It can also lead to issues with social and a strained parent-child relationship. Whereas it had been formerly assumed that children eventually outgrow ADHD, recent studies indicate that the bulk of affected people still show notable symptoms of the disorder into adulthood. Children with the disorder are at a bigger risk of long-term negative outcomes, like lower academic achievements and employment attainment.

Many ADHD symptoms, like high activity levels, involve remaining still for long periods of time and restricted attention spans, and are more common in young children. The distinction in young people with ADHD is that their hyperactivity and basic cognitive process are perceptibly bigger than expected for their age. Therefore, it causes distress and/or issues working at home, in school or with friends.

While children with ADHD may be social, their lack of secondary thought may cause problems in school. They do not wait for their chance to share their thoughts, interrupt others, may become enraged, take wild risks and their emotions may spill over. They can be hot-headed, act violently or have temper tantrums. All of this carries a significant social price. They may have trouble managing the time and energy to complete a goal, especially if it is something that does not interest them. Thankfully, doctors have found ways in which to treat this disorder.

Medication is usually a very important part of treatment for a child with ADHD. However, it may be a tough call to make as a parent, as these medications are usually strong in nature. The two main varieties of ADHD medications are stimulants and non-stimulants. Central systema nervosum (CNS) stimulants are the most commonly prescribed category of ADHD medication. These medications work by increasing the amounts of the brain chemicals referred to as Dopastat and monoamine neurotransmitters. The result improves a child’s concentration and helps them focus. Amphetamine-based stimulants (Adderall, Dexedrine, Dextrostat) are usually used to treat ADHD. However, these stimulants can have effects that are tough to handle. Stimulants like Adderall may cause heart palpitations, headaches and sleep disorders. These medications may even worsen the behaviors of one with ADHD by causing them to become infuriated or furious out of obscurity. However, non-stimulant medications also are another choice. They may be used once stimulants have not worked or have caused effects that a child finds onerous to handle. In addition, antidepressants like tricyclic antidepressant (Pamelor) may be used. Similarly to stimulants, non-stimulants have side effects. These may include lightheadedness and constant headaches.

Stimulants are the foremost common treatment in children and teenagers. This is often the kind of medication a doctor might attempt first. Stimulants are used for an extended time and are well-tested. They assist the brain management impulses and manage behavior. Non-stimulants are not as well tested. For many children, they rely on therapy and other behavioral related exercises. However, they are typically used together with stimulants, as that combination works most effectively.

When one has ADHD, typically the sole use of medications will not help counter the impact of dealing with ADHD. Behavioural medical care or psychotherapy will enable one to create an outlet for their emotions and learn to live in a very productive manner. At the end of the day, medical science has created several advancements with this disorder, and the current medications and choices for medical care are simply the beginning.

References

Dimarucut, Jenna. “ADHD.” HealthyChildren.org, 18 Feb. 2013, http://www.healthychildren.org/English/health-issues/conditions/adhd/Pages/default.aspx.&nbsp;

“Adhd Images.” Shutterstock, http://www.shutterstock.com/search/adhd. 

Mary S., Youth Medical Journal 2020

Categories
Health and Disease

The Health Benefits of Saliva

Abstract

Unbeknownst to many, saliva has many purposes, both inside and outside of our mouths.  Aside from it allowing for the mastication and swallowing of food, saliva from humans and other organisms have health benefits behind them that, although not as common in practicing medicine. It can provide insight and access to possible solutions, in emergency settings and for future clinical use.  In this paper, we take a look at the underlying science and the hidden properties of saliva, and how they can be applied in medicine for a variety of health concerns and problems, minor and possibly major. 

Introduction

Saliva is an extracellular oral fluid that is taken for granted. It serves many roles for different species, ranging from reptilian venomous drops to acting as a glue in construction of birds’ nests, thus demonstrating to have a diverse variety of functions [1]. 

Saliva production is stimulated by the sympathetic and the parasympathetic nervous system, and produced in the salivary glands, which are formed of clusters of acini cells. Secretion is controlled by the salivary centre composed of nuclei in the medulla [1].  In the human body, its main function is the preparation of food, from beginning the process of chemical digestion, to acting as a lubricant to make it easier to swallow, and even acting as a chemical carrier to taste cells.

However, it plays many more roles such as encouraging healing of wounds and tissue repair, protection and lubrication of our mouth, contributing to the upkeep of oral health and water balance [2].  Despite coming into contact with an abundance of microorganisms and flora found in or on the body, saliva protects our body from most of it, thus acting as one of the body’s strongest defence systems [3].  In addition to this, saliva holds a lot of power in diagnostics of many health issues and conditions including but not limited to: acne, allergies, heart conditions, cancer, and more [4]. 

Saliva is composed of 99.5% water, a variety of electrolytes, including sodium, potassium, calcium, magnesium, bicarbonate, and phosphates, as well as immunoglobulins, proteins, enzymes, mucins, and nitrogenous products, such as urea and ammonia [5,6]. 

Analysis of several studies have confirmed the importance of saliva in maintaining a healthy oral environment but it can also be used for purposes outside of the oral cavity in addition [7]. 

Oral Health

The oral cavity, in an average human, is estimated to have possibly as many as 8 million cells, with over 500 million bacterial cells per mL. Thus it is important to upkeep oral health in order to prevent different dental and oral diseases, and avoid foul odours from breath [6]. 

Saliva as a fluid constantly flushes the oral cavity of food debris, and keeps the mouth relatively clean [4].  However, from the moment teeth start to erupt in the oral cavity, saliva provides protection to the teeth on a more molecular basis. While the crown of the tooth is fully formed structurally, as it erupts, it is crystallographically incomplete.  So an interaction with saliva provides a post-eruptive maturation through diffusion of ions including calcium, magnesium, phosphorus, and fluoride, in addition to other molecules into the surface enamel. This maturation decreases permeability and absorption, increasing the hardness of the surface enamel, which has been shown to increase defence against cavities [5, 8].  Proline-rich proteins, statherin, and cysteine-containing phosphoproteins provide protection by effectively binding calcium and helping to maintain saliva with a high saturation calcium phosphate salts. They bind to the surfaces of early crystal nuclei and delay crystal growth [5]. 

Cystatins, a family of cysteine-containing proteins, have a minor role in regulating calcium levels in saliva. It is supposed that the main action of cystatins might be to inhibit the pathogenesis of periodontal disease [6]. 

Xerostomia, also known as dry mouth, is when an individual doesn’t produce enough saliva.  This can cause several problems to the individual such as difficulty ingesting food, foul breath, and the damage and weakening of the teeth [9].  As the flow of saliva is halted as one sleeps, in order to not choke, masses of bacteria can accumulate in the mouth, causing morning breath.[4] Lysozyme, an antibacterial enzyme present in saliva, which lyzes bacteria, preventing the overgrowth of microbial populations in the mouth [4]. The lack of saliva makes chewing and swallowing also difficult which often begins to affect an individual’s health. In order to treat xerostomia, doctors may prescribe saliva substitutes, which although can provide some temporary relief for the lack of moisture within the oral cavity. Saliva stimulants, parasympathomimetic drugs, organic acid and even lozenges are often used to stimulate the production of saliva.

Dental cavities/caries begins with acid dissolution of tooth minerals, initiated by acidogenic microorganisms in dental plaque which has been exposed to fermentable carbohydrate.  Macromolecule proteins and mucins serve to cleanse, aggregate, and/or attach oral microorganisms and contribute to dental plaque metabolism [6].  Individuals with xerostomia are more susceptible to dental caries because of the loss of the many protective factors in saliva [10]. 

Proline-rich proteins are also present, that contribute to the formation of the enamel, the outermost layer of teeth, as well as a substance capable of killing microbes in the oral cavity [6]. 

One major role of saliva is its participation in the formation of the acquired enamel pellicle (AEP) which is a protective layer that forms over teeth. The composition of the AEP selectively determines the types of microorganisms which can attach to the oral mucosa, thus protecting the enamel from any harmful molecules and damage. Because of the fairly rapid turnover of the cells in the oral mucosa, it is not possible for thick layers of biofilm to accumulate on them. The AEP is primarily a protein layer which covers all surfaces of the enamel and the underlying dentine or cementum when these have become exposed by loss of enamel, although the presence of certain lipids has also been reported [11]. 

Wound Healing

Wound healing involves four overlapping phases: hemostasis, inflammation, proliferation, and tissue remodelling.  The mouth is susceptible to wounds of various types, ranging from cheek biting to tooth extraction, and saliva plays an important role in the healing of all wounds [12]. Notably, oral wounds heal much faster than skin wounds and with relatively much less scar formation as proven by studies on pigs, and some studies suggest it is due to the properties of saliva[13]. 

Saliva contains nerve growth factor and epidermal growth factor, which have been found to accelerate the rate of wound healing [5, 10, 14, 15].  

Levels of stress have been proven to alter saliva composition and are in correlation to reduce wound healing.  Saliva contains catecholamines (hormones produced by the adrenal glands) and keratinocytes (outermost skin layer). These keratinocytes contain receptors which when activated, impair oral keratinocyte migration.  As levels of stress increase, the higher levels of catecholamines, which may cause delayed healing by their inhibitory action on oral keratinocytes [10].

Tadokoro et al.  showed that leptin, an anti-obesity hormone present in saliva, promotes wound healing by stimulating angiogenesis, the production of new blood vessels [15].  Likewise in 1942 Volker demonstrated that saliva speeds up blood flow, coagulation which leads to scabbing, in the specific areas, ultimately providing protection [5, 16]. 

Histatins are histidine-rich proteins which have also been found to be contributors to wound healing as it promotes cell migration observed in the oral cavity [17,18].  They hold antibacterial and antifungal properties.  Histatine-1, histatine-2, and histatine-3 promote the migration of oral keratinocytes within in vitro wound closure, improving the re-epithelialization phase [19-21]. 

Antimicrobial Aspects

As well as a diagnosis tool, many salivary components have anti-fungal, antibacterial and antiviral properties [22]. 

ANTIVIRAL:

Saliva has been found to eliminate or reduce the presence of influenza A as well as HIV [22]. The protein, salivary agglutinin(gp340) is encoded by the dmbt1 gene and has been found to be anti-HIV.  In 1997 gp340 was proven to inhibit the virus by binding to gp120 on the surface of the virus [22].  HIV is deemed not transmittable via the oral route due to the antiviral properties being able to inhibit and kill the virus [23]. 

Mucins are complex antiviral proteins which act by aggregation and encapsulation. Similarly to cell membranes and as a big component of mucus, they act by selectively modulating the adhesion of the virus to the surface of oral tissue by trapping the virus, controlling how they can enter the tissue and the colonization of viruses.

Von Ebner glands protein (VEGh) is a cysteine proteinase inhibitor protein. VEGh belongs to the lipocalin superfamily, the members of which possess very similar structural features.  Lipocalin, which is identical to VEGh possess endonuclease activity which may act as an antiviral and inhibit of RNA and DNA viruses [24] 

ANTIBACTERIAL: 

Saliva contains lysozyme, lactoferrin, salivary lactoperoxidase, and immunoglobulin A (IgA), all of which are antibacterial enzymes. It also contains thiocyanate, hydrogen peroxide and secretory immunoglobulin, which are also antibacterial compounds [6, 25].  

Lactoferrin, produced in intercalated ductal cells, binds ferric iron in saliva. This process makes ferric iron unavailable as a food source for microbes including cariogenic streptococci, that need iron to live [6].  This process of restricting and starving bacteria of vital nutrients is called nutritional immunity [6]. Lactoferrin is also capable of a bactericidal effect that is distinct from simple iron deprivation [5]. 

Peroxidase, also known as sialoperoxidase or lactoperoxidase, catalyzes bacterial metabolic by-products with thiocyanate, which is highly toxic to bacterial systems [6, 26].  Secreted by acinar cells, peroxidase also protects mucosa from the strong oxidizing effects of hydrogen peroxide produced by oral bacteria [6]. Salivary peroxidase is part of an antibacterial system.  This system involves oxidising salivary thiocyanate with hydrogen peroxide which is generated by oral bacteria to hypothiocyanite and hypothiocyanous acid. These products, in turn, affect bacterial metabolism, particularly acid production, by oxidizing the sulfhydryl groups of the enzymes involved in glycolysis and sugar transport. The antimicrobial effect of salivary peroxidase against the bacteria S. mutans is increased by interacting with secretory IgA [5]. 

Immunologic contents of saliva include secretory IgA, IgG, and IgM. Nonimmunologic salivary contents are selected proteins, mucins, peptides, and enzymes [27].  Nonimmunologic antibacterial salivary contents such as proteins, mucins, peptides, lactoferrin, lysozyme, and peroxidase, protect teeth against physical, chemical, and microbes and threats [6]. 

Secretory IgA, the largest immunologic component of saliva, is an immunoglobulin produced by plasma cells in connective tissues and translocated through the duct cells of major and minor salivary glands. IgA, while active on mucosal surfaces, also acts to neutralize viruses, serves as an antibody to bacterial antigens, and works to aggregate or clump bacteria, thus inhibiting bacterial attachment to host tissues [6]. 

Proteins such as glycoproteins, statherins, agglutinins, histatins, and proline-rich proteins act by aggregating bacteria. Clumping the microorganisms reduces the ability of bacteria to stick to hard or soft tissue oral surfaces, spreading throughout the oral cavity and thereby controls bacterial, fungal, and viral colonization [6, 28].

 Although saliva has numerous antibacterial functions, it supports and contributes to the selective growth of bacteria and non-cariogenic microflora [6].  For example some probiotics including lactobacilli can fight harmful bacteria in the oral cavity and can help to heal gum disease, plaque buildup and inflammation [30].

Conclusion

From creating protective layers on the teeth, to increase scabbing for wound healing for preventative measures, and encapsulating and lysing bacteria and viruses in the mouth, saliva has far more health benefits and qualities that more than often go unnoticed.    In contrast to the common connotations of saliva within society being disgusting and offensive, saliva holds so much power within medicine, being a diagnostic tool, a protector and a healer. 

References

[1] Miletich I. (2010). Introduction to salivary glands: structure, function and embryonic development. Frontiers of oral biology, 14, 1–20. https://doi.org/10.1159/000313703 

[2] Mandel I. D. (1987). The functions of saliva. Journal of dental research, 66 Spec No, 623–627. https://doi.org/10.1177/00220345870660S203 

[3] Green, G. E. (1966). Inherent defense mechanisms in saliva. Journal of Dental Research, 45(3), 624-629. 

[4] Tiwari M. (2011). Science behind human saliva. Journal of natural science, biology, and medicine, 2(1), 53–58. https://doi.org/10.4103/0976-9668.82322 

[5] Kumar, B., Kashyap, N., Avinash, A., Chevvuri, R., Sagar, M. K., & Kumar, S. (2017). The composition, function and role of saliva in maintaining oral health: a review. International Journal of Contemporary Dental & Medical Reviews, 2017

[6] Humphrey, S. P., & Williamson, R. T. (2001). A review of saliva: normal composition, flow, and function. The Journal of prosthetic dentistry, 85(2), 162-169. 

[7] Dodds, M. W., Johnson, D. A., & Yeh, C. K. (2005). Health benefits of saliva: a review. Journal of dentistry, 33(3), 223–233. https://doi.org/10.1016/j.jdent.2004.10.009 

[8] Azen, E. A. (1993). Genetics of salivary protein polymorphisms. Critical Reviews in Oral Biology & Medicine, 4(3), 479-485. 

[9] Cooke, C., Ahmedzal, S., & Mayberry, J. (1996). Xerostomia—a review. Palliative medicine, 10(4), 284-292. 

[10] Dawes, C., Pedersen, A. M. L., Villa, A., Ekström, J., Proctor, G. B., Vissink, A., … & Sia, Y. W. (2015). The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI. Archives of oral biology, 60(6), 863-874.] 

[11] Hannig, M., & Joiner, A. (2006). The structure, function and properties of the acquired pellicle. In The teeth and their environment (Vol. 19, pp. 29-64). Karger Publishers. 

[12] Rodrigues Neves, C., Buskermolen, J., Roffel, S., Waaijman, T., Thon, M., Veerman, E., & Gibbs, S. (2019). Human saliva stimulates skin and oral wound healing in vitro. Journal of tissue engineering and regenerative medicine, 13(6), 1079–1092. https://doi.org/10.1002/term.2865 

[13] Haekkinen, L. A. R. I., UITTO, V. J., & Larjava, H. (2000). Cell biology of gingival wound healing. Periodontology 2000, 24(1), 127-152. 

[14] Noguchi, S., Ohba, Y., & Oka, T. (1991). Effect of salivary epidermal growth factor on wound healing of tongue in mice. The American journal of physiology, 260(4 Pt 1), E620. 

[15] Tadokoro, S., Ide, S., Tokuyama, R., Umeki, H., Tatehara, S., Kataoka, S., & Satomura, K. (2015). Leptin promotes wound healing in the skin. PLoS One, 10(3), e0121242. 

[16] Volker, J. F. (1939). The effect of saliva on blood coagulation. American Journal of Orthodontics and Oral Surgery, 25(3), 277-281. 

[17] Edgar, W. M., O’Mullane, D. M., & Dawes, C. (Eds.). (2004). Saliva and oral health (Vol. 146). London: British Dental Association. 

[18] Brand, H. S., & Veerman, E. C. (2013). Saliva and wound healing. Chin J Dent Res, 16(1), 7-12. 

[19] Torres, P., Castro, M., Reyes, M., & Torres, V. A. (2018). Histatins, wound healing, and cell migration. Oral diseases, 24(7), 1150-1160. 

[20] Oudhoff, M. J., Kroeze, K. L., Nazmi, K., van den Keijbus, P. A., van’t Hof, W., Fernandez-Borja, M., … & Veerman, E. C. (2009). Structure‐activity analysis of histatin, a potent wound healing peptide from human saliva: cyclization of histatin potentiates molar activity 1000‐fold. The FASEB Journal, 23(11), 3928-3935. 

[21] Oudhoff, M. J., Blaauboer, M. E., Nazmi, K., Scheres, N., Bolscher, J. G., & Veerman, E. C. (2010). The role of salivary histatin and the human cathelicidin LL-37 in wound healing and innate immunity. Biological chemistry, 391(5), 541-548. 

[22] Malamud, D., Abrams, W. R., Barber, C. A., Weissman, D., Rehtanz, M., & Golub, E. (2011). Antiviral activities in human saliva. Advances in dental research, 23(1), 34–37. https://doi.org/10.1177/0022034511399282 

[23] Fox, P. C., Wolff, A., Yeh, C. K., Atkinson, J. C., & Baum, B. J. (1988). Saliva inhibits HIV-1 infectivity. Journal of the American Dental Association (1939), 116(6), 635–637. https://doi.org/10.14219/jada.archive.1988.0002 

[24] Amerongen, A. N., & Veerman, E. C. I. (2002). Saliva–the defender of the oral cavity. Oral diseases, 8(1), 12-22. 

[25] Bjornesjo, K. B. (1950). Studies on the antibacterial factors of human saliva. Acta chem. scand, 4, 835-845. 

[26] Tenovuo, J., & Knuuttila, M. L. (1977). Antibacterial effect of salivary peroxidases on a cariogenic strain of Streptococcus mutans. Journal of dental research, 56(12), 1608-1613. 

[27] Vila, T., Rizk, A. M., Sultan, A. S., & Jabra-Rizk, M. A. (2019). The power of saliva: Antimicrobial and beyond. PLoS pathogens, 15(11), e1008058 

[28] Thompson, R., & Shibuya, M. (1946). The inhibitory action of saliva on the diphtheria bacillus: the antibiotic effect of salivary streptococci. Journal of bacteriology, 51(6), 671. 

[29] Van Kesteren, M., Bibby, B. G., & Berry, G. P. (1942). Studies on the antibacterial factors of human saliva. Journal of bacteriology, 43(5), 573. 

[30] Baker, J. L., & Edlund, A. (2019). Exploiting the oral microbiome to prevent tooth decay: Has evolution already provided the best tools?. Frontiers in microbiology, 9, 3323.

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Health and Disease

Melanoma: 5 Types of Skin Cancer

Melanoma is a form of a skin cancer that develops from melanocytes, the cells that produce the pigment (melanin) for one’s skin. The exact cause of melanoma is unidentified, however, studies have shown how melanoma can be caused due to an unhealthy amount of exposure to ultraviolet radiation (UV light). The most common types of melanoma include nodular melanoma, lentigo maligna, superficial spreading, and acral lentiginous. Ocular melanoma is classified as an uncommon or rare type of melanoma skin cancer.

Superficial Spreading Melanoma

As superficial spreading melanoma makes up 70% of all types of melanoma skin cancers, it is classified as the most common type of melanoma. It can appear in a mole or it can spread to new, deeper areas within the patient’s body. The process of the cancer spreading across the skin’s surface is known as radial growth, while the process of the cancer spreading deeper within the patient is known as vertical growth. A superficial spreading melanoma is known to appear everywhere on a person’s body. However typically for males it can be found on their torso or upper back and for females it can be found on their legs or upper back. It typically starts on the central body part. When trying to find this type, look for a flat or thin and a discolored or asymmetrical patch with rough surroundings. In terms of color, this type is known to appear in shades tan, brown, red, pink, lack, white, or blue. But, it can also lack pigment and look like a melanotic lesion.

Lentigo Maligna

Lentigo melanoma is commonly found in the older population. In terms of statistics, this melanoma skin cancer makes up approximately somewhere in between 10 to 15 percent of all the four main types. This type of cancer begins by growing near one’s skin or one’s epidermis before spreading to other areas of the human body. It mainly starts in those areas of the skin that are the most affected by sun damage. Like the superficial spreading melanoma, lentigo maligna looks flat or thin patch with a rough surrounding. Its colors range from tan to brown, dark brown, or blue-black. In its initial stages of growth on a patient’s skin, this type is known as Lentigo Maligna. But as the years go by and this disease starts affecting deeper parts of the human body, this disease known as lentigo maligna melanoma.

Acral lentiginous melanoma

Acral lentiginous melanoma is generally found in populations with darker skin tones or those with more melanin. For example, it is common for those with an African or HIspanic background to contract this disease. Acral lentiginous melanoma accounts for less than 5 percent of all the types of melanoma and is not caused by sun exposure. They appear in less obvious places within the human body, such as underneath one’s finger nails, making it harder to accurately diagnose and identify it in patients. To the human eye, they generally look like a flat and small spot of skin and are either black or dark brown.

Nodular Melanoma

After superficial spreading melanoma, Nodular Melanoma takes the place of the most common type of skin cancer, by making up approximately 15 to 20% of all types. It is known to spread the most quickly out of all the other types of melanoma and it tends to grow deep into one’s skin. Nodular Melanoma resembles a polypoid, as the lesion itself tends to to stick out from the patient’s skin. In terms of color, it can be black, pink, red, or mimic your skin color. Typically, this disease begins on one’s chest, face, back, or any part of the skin that receives minimal sun exposure.

Ocular Melanoma

Ocular melanoma, the type that takes place in one’s eye affects the cells that create pigment. Making up only 3% of all types of melanoma, ocular melanoma is classified as a very rare disease. However it takes the place as the most common type of eye cancer that occurs in adults.This disease begins in the second or the middle layer of the eye, which is known as the uvea. It is uncommon to find this type of melanoma to affect the conjunctiva of a patient’s eye. Due to the fact that ocular melanoma develops in the middle part of the eye, it isn’t possible for one to notice it in their day to day life, unlike other forms of melanoma. Making it even harder to find, ocular melanoma doesn’t cause any sort of symptoms or early signs of its appearance.

References:

Types of melanoma skin cancer – Canadian Cancer Society. (n.d.). Retrieved August 13, 2020, from https://www.cancer.ca/en/cancer-information/cancer-type/skin-melanoma/melanoma/types-of-melanoma/?region=on

Melanoma. (2020, March 10). Retrieved August 13, 2020, from https://www.mayoclinic.org/diseases-conditions/melanoma/symptoms-causes/syc-20374884

Melanoma. (2020, June 19). Retrieved August 13, 2020, from https://www.skincancer.org/skin-cancer-information/melanoma/

The Seven Different Types of Melanoma Skin Cancer. (2019, October 03). Retrieved August 13, 2020, from https://melanomaknowmore.com/types-of-melanoma/

Categories
Health and Disease

Palliative Care

Clinical advancements and increasing access to global healthcare have pushed life expectancy by 26.2 years since 1950, making it seem that modern medicine is on the right path. These treatments come at a great cost not only to patients’ health but also their quality of life, with 52% of terminal patients in severe pain (Weiss, 2001). More shockingly though with 17% of the patients expressing a desire for death, (Guy M, 2006;) one wonders whether the possible solace is worth it. In modern medicine’s search for the ‘elixir of life’, has it forgotten its oath of relief from pain and suffering?

The concept of palliative medicine began in 1967 with British nurse Dame Cicely Saunders’s construction of the first hospice centre. The concept was also put forth into Kubler-Ross’s book “On Death and Dying”. By dividing death into 5 stages of death, Kubler-Ross began to educate the world about the process of death. Based on these principles, palliative care has evolved into a medical approach that focuses on prevention and relief from any kind of physical, psychological, social, and spiritual pain and suffering that is experienced by patients and their families. It allows an individual to maintain their dignity and improves their quality of life while undergoing treatment. While cardiovascular diseases (38.3%) and cancer (34%) patients require palliative care most often, it can be administered for a variety of other terminal illnesses and aggressive treatments. (World Health Organization, 2016)

Palliative care can be delivered in various forms, such as at a hospital or community care centre. In-house palliative care is difficult but family members often do it as they feel an obligation or want to feel connected to their loved ones. End of Life care/Hospice care, as defined by American health insurance plans, refers to the pain relief care given to terminally ill patients with a 6-month prognosis of survival, which results in the end of curative or experimental treatments. Paediatric palliative care is required for over 1.2 million children, and it has a special focus on the relationships between children and their families. A palliative care team is made up of a general physician, nurses, cancer and pain specialists, therapists, and a range of physiotherapists, spiritual leaders, and social workers.

Palliative care begins with the team of specialists talking with the individual, their family, and other doctors involved in their treatment to devise a plan based on resources available and the individual’s wishes.  The patient’s symptoms are assessed with the Edmonton Symptom Assessment Scale (ESAS), which evaluates levels of pain, nausea, anxiety, and other factors over a 10-point scale for severity. Physical symptoms are managed with basic, readily available medication. However, as a patient’s ability to swallow is compromised, subcutaneous injections, or even rectal doses via a special catheter, may be opted over oral drugs. The analgesic ladder as developed by the World Health Organization is often used as a basis for pain management through a combination of opioids, pain relief drugs like fentanyl, and adjuvants, such as muscle relaxants and sedatives.

  1. Non-opioid (e.g. paracetamol) ± adjuvant (e.g. nortriptyline for neuropathic pain).
  2. Weak opioid (e.g. codeine) + non-opioid ± adjuvant.
  3. Strong-opioid (e.g. morphine) + non-opioid ± adjuvant.

Terminal illnesses are often stigmatized in society, because treatment may result in body disfigurement that can affect an individual’s self-worth, interpersonal relationships, and body image. Facing the idea of mortality may also lead to anxiety and depression for both an individual and their family. A psychosocial team organizes psychological counseling and other therapies based on a patient’s interests. For example, water, pet, or music therapy may also be experimented with to increase pain relief. Family support groups, which get the patient and his/her family in contact with similar patients and their families, may also be conducted. Such a forum encourages an increase in medical knowledge on the disease condition, allows the exchange of experiences, as well as promotes good interpersonal and family relationships. Spiritual leaders can help provide patients with care during the existential crisis and help them become comfortable with the idea of death. Bereavement support provides individuals and families with an outlet for their frustrations, anger, and grief.

Palliative care has shown to reduce pain and other distressing symptoms while helping patients and families confronting mortality. It has also shown to provide some patients with an extra 10 months of high quality of life past the original prognosis (Rowland, 2010). However, a 2017 WHO report estimated that out of the 40,000,000 people across the globe needing some form of palliative care, only 14% of them are receiving it. This leads to the question: why is it so difficult to provide basic pain relief to patients?

In the United States, over a third of hospitals, with more than 50 beds  (Halwey, 2017), lack a palliative program mainly because Medicare and other insurance plans only cover hospice care but fail to cover palliative care. Furthermore, despite reducing medical costs by $4,098 for patients who were released after palliative care, it continues to be funded by philanthropy or fee-services. Lack of funding also means that the integration of palliative care units into existing hospitals is difficult, and as in-house care is too expensive, most patients do not receive it. As hospitals lack a palliative care unit,  doctors/nurses are unable to do palliative care rotations and are less familiar with the process and its benefits. This means that palliative care is often not even suggested as an option to terminal patients. In addition, the absence of proper education has resulted in the spread of misconceptions such as that palliative care hastens death or no curative treatments can be tried. Most importantly, though, is the misconception that palliative care is only about patients, while in reality, it focuses much more on creating healthy family relationships and helping families through the grieving process.

All the barriers can usually be traced back to a very basic human fear, the fear of death. Thanatophobia, or death anxiety, is caused by various reasons such as the fear of the dying process, losing control, or appearing weak and vulnerable. As Elisabeth Kubler-Ross stated, “It is difficult to accept death in this society because it is unfamiliar. In spite of the fact that it happens all the time, we refuse to see it.” What this has resulted in is a society that is unwilling to accept our mortality, where doctors are overly optimistic in prognosis, and patients living in denial. Thus, people choose higher risk treatments to avoid death just a bit longer and palliative research receives less funding in hopes of a cure.

Making society accept our mortality is the first step in making palliative care globally accessible. Doing so will not only open up new funding avenues, but it will also encourage doctors/nurses to specialize in palliative medicine. Readily available palliative care will give people the courage to power through, or enjoy a few months of quality life. No matter what, palliative care has the power to realign the goals of modern medicine by keeping patients’ best interests at heart.

References

  • C., O. T. (2010). Psychosocial issues in palliative care: a review of five cases. Indian journal of palliative care, 16(3), 123–128. DOI:10.4103/0973-1075.73642
  • Gary, S. (2017). Thanatophobia (Death Anxiety) in the Elderly: The Problem of the Child’s Inability to Assess Their Own Parent’s Death Anxiety State. Frontiers in Medicine, Volume 4, Pages 11.
  • Guy M, S. T. (2006;). The desire for death in the setting of terminal illness: a case discussion. Prim Care Companion J Clin Psychiatry, 8, (5):299-305. DOI:10.4088/pcc. v08n0507 .
  • P., H. (2017). Barriers to Access to Palliative Care. Palliative Care, 10. DOI:10.1177/1178224216688887
  • Rowland, K. &. (2010). PURLs. Palliative care: earlier is better. The Journal of family practice, 59(12), 695–698.
  • Weiss, S. C. (2001). Understanding the experience of pain in terminally ill patients. Lancet, 357(9265), 1311-1315. DOI:10.1016/S0140-6736(00)04515-3
  • World Health Organization. (2016). Planning and Implementing Palliative Care Services: a guide for programme managers. ISBN: 978 92 4 156541

Categories
Health and Disease

Alport Syndrome In Women

What is Alport Syndrome?

Alport Syndrome is a genetically inherited kidney disease. It is caused by genetic mutations of the collagen IV family of proteins, which are a major part of basement membranes present in all tissues, including the kidney, inner ear, and eye. Genetic mutations of collagen IV (COL4A5 is situated on the X chromosome, while COL4A3 and COL4A4 are situated on chromosome 2) cause thinning and splitting of the glomerular basement membrane. X-linked Alport Syndrome (XLAS) is caused by mutations in the COL4A5 gene which encodes the collagen IV α5 chain . Autosomal recessive disease is caused by two mutations in trans (on different chromosomes) in the COL4A3 or COL4A4 genes, which are code for the collagen IV α3 and α4 chains, respectively. The collagen IV α3, α4, and α5 chains form a heterotrimer that is the predominant network of the basement membranes of the glomerular filter, the cochlea, cornea, lens capsule, and retina. The collagen IV heterotrimer consists of a long series of Gly-Xaa-Yaa repeats, where Gly is present at each third residue, and X and Y are often hydroxyproline and proline. This process leads to scarring throughout the kidney, and may later lead to kidney failure. It may also cause abnormalities in the ears and eyes, which can lead to vision and hearing loss.

Symptoms:

Hematuria – Blood in urine

Abnormal urine color

Proteinuria – Large amounts of protein “spilling” into the urine

Foamy urine

Edema – Swelling in parts of the body, most noticeable around the eyes, hands and feet, and abdomen

Low Blood Albumin Levels

Flank pain

Decreased or loss of vision (more common in males)

Loss of hearing (more common in females)

High Cholesterol in some cases

High Blood Pressure in some cases

Tendency to form Blood Clots if spilling large amounts of protein

Kidney Failure (in only some cases) as the disease progresses

Types:

1)CLASSIC Alport Syndrome: X-linked syndrome with haematuria, sensorineural deafness, and conical deformation of the anterior lens surface(lenticonus)

2)X-LINKED FORMED ASSOCIATED with diffuse leiomyomatosis

3)AUTOSOMAL RECESSIVE FORM 

4)AUTOSOMAL DOMINANT FORM 

Autosomal dominant and recessive forms both cause renal disease without deafness or lenticonus.

INTRODUCTION OF Alport Syndrome IN WOMEN:

Many renal physicians think of Alport Syndrome as primarily affecting men. However, twice as many women are also affected by X-linked Alport Syndrome. The women who are affected are commonly undiagnosed. Half of their sons and daughters are also affected. Recessive inheritance is suspected when women develop early-onset renal failure or lenticonus. Their family may be consanguineous. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. 

X-LINKED Alport Syndrome(XLAS):

In cases of X-linked inheritance, the genetic defect causing the disease is on the X chromosome. Since men, unlike women, have only one copy of the X chromosome, X-linked Alport Syndrome is more likely to affect men. Women with one faulty copy of the X chromosome can develop the disease, but it is usually less severe in women because their other X chromosome can compensate. Most go undiagnosed or underdiagnosed due to variations in symptom severity and course of disease progression. Between 15 and 30 % of women with XLAS develop kidney failure by the age of 60 and symptoms of hearing loss by their middle ages.

X-CHROMOSOME INACTIVATION IN WOMEN:

Women have two copies of the X chromosomes, but one of them is randomly turned off or inactivated during development in a process called LYONIZATION. Thus, in each cell, there is only one active X chromosome and one inactive X chromosome. Since lyonization is random in people and varies from cell to cell, the X chromosome that remains active may either be carrying the normal gene or the defective gene. Depending on the proportion of cells in which the normal X chromosome is active, the symptoms can vary from no symptoms at all to those that are quite severe.

Sometimes, X chromosome inactivation can be preferential (also called skewed X-Inactivation) and the normal X chromosome can be unfavored, resulting in most cells expressing the mutated gene. Such women can be as severely affected by XLAS as men.

A MISCONCEPTION OF Alport Syndrome TO AFFECT ONLY MALE AND NOT FEMALE:

X-linked Alport Syndrome is underdiagnosed or undiagnosed in women, which is observed in generational skipping. This occurs because female relatives of affected men are not systematically screened in adult nephrology practice.

A male with X-linked disease has inherited the disease from his mother in 85% of cases. On average, half of the male’s affected family include his sisters, brothers, and daughters, but none of his sons.

For females with X-linked disease, the situation is more complex since the disease can be inherited from her father or mother. If a woman inherits the disease from her father, then all of her sisters are also affected, but if she inherits the disease from her mother, then half of her sisters and half her brothers are also affected. In addition, half an affected woman’s sons and half her daughters are affected.

Clinical features of Alport Syndrome in women:

Clinical features in females depend on mutation type and “lyonization.” Lyonization produces a mosaic distribution of the mutant collagen IV α5 chain and disease in the female kidney and skin. This may result in a normal clinical phenotype (a severe or an intermediate), and the staining pattern for diagnostic testing may be confusing.

Hematuria: Nearly all females with X-linked Alport Syndrome have persistent hematuria from infancy. The presence of even short stretches of lamellation suggests Alport Syndrome.

Albuminuria: Albuminuria is not well-studied in women with Alport Syndrome. 

ESRD: 30% of all women with X-linked Alport Syndrome develop ESRD by the age of 60. Affected women should be strongly advised not to donate a kidney to an affected male relative, even when urine protein excretion is normal. This is because of their own risk of ESRD. It is important, though, to confirm genetically if the mother is actually affected because of the small chance (15%) of a de novo mutation in her son.

Autosomal recessive Alport Syndrome: It affects about one in 40,000 individuals, and is suspected in young women with renal failure and hearing loss, or lenticonus. The family may be consanguineous. Typically, the only other affected family member, if any, is a sibling. The affected woman’s parents, grandparents, and children may have hematuria and thin basement membrane nephropathy, but do not develop renal failure.

DIAGNOSIS OF Alport Syndrome IN WOMEN:

Women with Alport Syndrome should be identified at an early age once proteinuria appears.

Accurate diagnosis of Alport Syndrome in girls and women can be challenging because many affected females exhibit only microscopic haematuria and glomerular basement membrane attenuation. In such patients, family history and immunohistochemical analysis of type IV collagen expression in basement membranes of the skin or kidney may be helpful. Alport Syndrome should be suspected in women with haematuria and a positive family history of kidney failure. A negative family history for renal failure does not, however, exclude a diagnosis of Alport Syndrome. In some women with longstanding haematuria, a diagnosis of Alport Syndrome is established only after the diagnosis is made in a child. An individualized approach should be taken toward female members of Alport Syndrome whose haematuria is associated with atypical symptoms, such as dysuria or flank pain, or unexpectedly severe abnormalities of renal function, such as heavy proteinuria or azotemia at a young age.

Type IV IHC abnormalities that are distinguishing characteristics in females include-

I) Typical ARAS female-Renal basement membranes are entirely negative for the α3(IV) and α4(IV) chains, and glomerular basement membranes are completely negative for the α5(IV) chain, reflecting the failure to deposit α3α4α5(IV) trimers.

II) Bowman’s capsules, distal tubular basement membranes and EBM are positive for α5(IV) chains, because formation and deposition of α5α5α6(IV) trimers are preserved.

RENAL DIAGNOSIS IN WOMEN WITH Alport Syndrome:

Renal transplantation is usually very successful in women with Alport Syndrome who progress to end-stage renal failure. Even though anti-GBM nephritis of the renal allograft occurs in about 3% of transplanted Alport males, the risk of this complication in females with XLAS should theoretically be close to zero. Women with ARAS, due to certain COL4A3 mutations, can develop anti-GBM nephritis of the allograft.

By Pratiksha Baliga (India), Youth Medical Journal

Reference sites:

“Alport Syndrome.” NephCure Kidney International, nephcure.org/livingwithkidneydisease/understanding-glomerular-disease/other-glomerular-diseases/alport-syndrome-2/.

Kashtan, Clifford E. “Alport Syndrome and the X Chromosome: Implications of a Diagnosis of Alport Syndrome in Females.” OUP Academic, Oxford University Press, 29 Mar. 2007, academic.oup.com/ndt/article/22/6/1499/1926063.

Naqvi, Erum. “Alport Syndrome in Women.” Alport Syndrome News, Bionews Services, 25 Apr. 2018, alportsyndromenews.com/alport-syndrome-in-women/.

Savige, Judy, et al. “Alport Syndrome in Women and Girls.” Clinical Journal of the American Society of Nephrology : CJASN, American Society of Nephrology, 7 Sept. 2016, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012472/.