NURS 6501 Week 1 Discussion: Alterations in Cellular Processes Sample Essay

nurs 6501 week 1 discussion: alterations in cellular processes sample essay

NURS 6501 Week 1 Discussion: Alterations in Cellular Processes Sample Essay

NURS 6501 Week 1 Discussion Alterations in Cellular Processes Sample Essay

Genetics role in drug addiction.

According to (Genetics, 2022), Genetics is the scientific study of genes and heredity—how certain qualities or traits are passed from parents to offspring because of changes in DNA sequence. A gene is a DNA segment containing instructions for building one or more molecules that help the body work. For our society to understand the individual’s characteristics, genetics is researched to formulate treatments within their hereditary makeup. Genetics plays a huge part in drug addiction because it aids the healthcare provider in how to treat specific upyield adverse drug reactions. In this case study, Narcan is a drug that was used to displace opioids from the receptors of the CNS dropping double enone bond to a single bond.

Symptoms

Symptoms are the body’s reactions to letting the individual know there is an issue within one of the components of the body’s systems. A symptom (King, 1968) is a manifestation of a disease that appears to the patient himself, while a sign is a manifestation of the disease that the physician perceives. The sign is objective evidence of disease; a symptom is subjective. Symptoms represent the patient’s complaints; if severe, that complaint is measured. For example, in this scenario, the client woke up complaining of burning over his left leg, hip, and arm.

The assessment reveals that tissues in these areas are necrotic. According to (A.D.A.M Inc 1997-2023), Necrosis is the death of body tissue. It occurs when too little blood flows to the tissue. Necrosis can be from injury, radiation, or chemicals. Necrosis cannot be reversed. The client’s tissues in these areas were not receiving the correct blood supply or oxygenation for an unknown period. The proper amount of oxygenated blood supply is needed for tissues to function correctly in the body

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Physiologic response

The client in this scenario displays a physiologic response derived from the brain and CNS system. The brain and the CNS system control a multitude of automatic bodily functionsOpioids can depress the brain and CNS causing the body to shut down in a state of unconsciousness. According to (Opioid Addiction: MedlinePlus Genetics, 2017), an overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately. Opioids are known to cause many other physiologic responses. Researchers have shown (Dhaliwal, 2022) Opioid receptors are present in cardiac tissue; their activation leads to hyperpolarization of membranes and activation of the vagus nerve this can explain the clients EKG findings. These changes result in peripheral vasodilation and bradycardia, which ultimately causes hypotension. Peripheral vasodilation gets further exacerbated by systemic histamine release.

Cells Involved

There are several cells involved with opioid Tolerance. According to (Genetic Science Learning Center, 2013), Tolerance happens through changes at the cellular level, the G protein-coupled receptors (GPCRs) that control most of the body’s autonomic functions. These proteins activate the cAMP response, which in turn, PKA responds. According to (Dhaliwal, 2022), Recent advances in technology have elicited activation of G protein-dependent inward rectifying potassium channels (GIRK) on stimulation of GiCPR by agonists, including opioids, through the interaction of the G-beta-gamma subunit to the Kir channels. New and upcoming reports have documented modulation of the MAPK/ERK pathway (Mitogen-activated protein kinase), which is involved in various cellular processes, including cell proliferation, differentiation, and apoptosis. It results from the brain restoring balance after repeatedly overstimulating by a drug. As the balance is restored, neurons, synapses, and entire brain regions work differently. The brain sets a new normal that includes the effects of the drug.

Based on genetics and gender.

According to (Bezrutczyk, 2023), women develop a dependence on opioids faster than men due to a heightened dopamine response in the brain. Men’s motility is higher due to their addiction to the drug. Researchers (Goodyear et al., 2022) showed that the White individual had higher stigma ratings compared to the Black individual (range of partial η2 = 0.002–0.004). An interaction effect demonstrated that a White female was rated higher responsible for opioid use than a Black female (Cohen’s d = 0.21). A Black male was rated with higher responsibility for opioid use than a Black female (Cohen’s d = 0.26). Last, we showed that a male and an individual who transitioned to heroin had higher stigma than a female and an individual who continued to use prescription opioids (range of partial η2 = 0.004–0.007).

References

A.D.A.M Inc. (1997-2023). Necrosis: MedlinePlus Medical Encyclopedia. Retrieved February

27,2023from https://medlineplus.gov/ency/article/002266.htm#:~:text=Necrosis%20is%20the%20death%20of,injury%2C%20radiation%2C%20or%20chemicals.

Bezrutczyk, D. (2023, February 9). The Differences in Addiction Between Men and Women – Addiction

Center. Addiction Center. Retrieved February 28, 2023, from https://www.addictioncenter.com/addiction/differences-men-women/#:~:text=Furthermore%2C%20women%20develop%20a%20dependence,as%20a%20result%20of%20abuse.

Dhaliwal, A. (2022, July 25). Physiology, Opioid Receptor. StatPearls – NCBI Bookshelf.

Retrieved February 28, 2023, from https://www.ncbi.nlm.nih.gov/books/NBK546642/#:~:text=Opioid%20receptors%20are%20present%20in,bradycardia%2C%20which%20ultimately%20causes%20hypotension

Genetic Science Learning Center. (2013, August 30) Opioids and the Physiology of Tolerance. Retrieved

February 21, 2023, from https://learn.genetics.utah.edu/content/addiction/tolerance

Goodyear, K., Ahluwalia, J. S., & Chavanne, D. (2022). The impact of race, gender, and heroin use on

opioid addiction stigma. Journal of Substance Abuse Treatment, 143, 108872. https://doi.org/10.1016/j.jsat.2022.108872

King, L. S. (1968). Signs and Symptoms. JAMA, 206(5), 1063. https://doi.org/10.1001/jama.1968.03150050051011

Opioid addiction: MedlinePlus Genetics. (2017, November). Retrieved February 27, 2023,

from https://medlineplus.gov/genetics/condition/opioid-addiction/

U.S. Department of Health and Human Services. (2022, May 4). Genetics. National Institute of General Medical Sciences. Retrieved February 27, 2023, from https://nigms.nih.gov/education/fact-sheets/Pages/genetics.aspx#:~:text=Genetics%20is%20the%20scientific%20study,that%20help%20the%20body%20work.

Role of Genetics

This scenario presents a 16-year-old boy with a chief complaint of sore throat is one of the most commonly diagnosed diseases with an estimated 15 million annual healthcare visits in the primary care settings (Rogers & Eastland, 2021).  Rapid strep test confirms positive strep throat.  The most common cause of pharyngitis is Streptococcus pyogenes also known as group A Streptococcus (GAS). The colonization, invasion, and dissemination of the microorganism often transmitted through, contact, droplet, and airborne (Rogers & Eastland, 2021). The genetic and immunologic predisposition helps to fight the repeated infection that can have a negative impact on health.

A large amount of virulence factor can be producing by GSC to overcome host immunity (Chauhan et al., 2016). However, one of the studies identified M protein, a cell surface antigen that is antiphagocytic and protective in some strains where the cloning of the M protein gene also known as emm gene has led to the identification and sequencing of the genotypes to classify GAS (Khosravi et al., 2016). The emm gene tying has helped to early identification of the patient with the GAS pharyngitis identification and early treatment with appropriate antibiotics (Khosravi et al., 2016). In addition to NURS 6501 Week 1 Discussion: Alterations in Cellular Processes Sample Essay, the generic linkage IgE antigen and allergen cause hypersensitivity leading to anaphylactic shock.

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Patients’ Clinical Presentation and Physiological Response

In this scenario, the invasion of the patient first line of defense nasopharynx and oropharynx by the

nurs 6501 week 1 discussion alterations in cellular processes sample essay
NURS 6501 Week 1 Discussion Alterations in Cellular Processes Sample Essay

pathogen has resulted in an inflammatory response (Rogers & Eastland, 2021).  The highly adaptive GAS pathogens maintain cellular integrity by adhering to the biological host. Microorganisms colonize the oropharyngeal mucosal epithelium of the respiratory tract (Rogers & Eastland, 2021). Signs such as fever and positive anterior and posterior adenopathy increase the number of circulating leukocytes. The swelling reddened and white exudate of the pharynx on tonsils that are enlarged to 3+ are consistent with innate defense mechanisms to get rid of the undesired pathogen. Patient innate immunity has an inflammatory response that is trying to neutralize and destroy invading bacteria trying to limit the spread and damage to the tissue (Rogers & Eastland, 2021).

Moreover, the allergic drug reaction to the medication amoxicillin caused adverse event triggering   hypersensitivity. The patient sign and symptoms of swelling of tongue, difficulty breathing, and audible wheezing are consistent with the anaphylactic reaction which is medicated by sensitized mast cell, and IgE to produce antibodies resulting in vascular permeability, vasodilation, bronchoconstriction, and emigration of leukocytes to the infected area (Miguel-Rodriquez et al., 2018).

The cells involved in this process: NURS 6501 Week 1 Discussion: Alterations in Cellular Processes Sample Essay

The nasopharynx consists of pseudostratified columnar epithelium cells which are linked to trap the unwanted organisms (Rogers & Eastland, 2021). The tonsils and adenoids contain immunologic cells to attack undesired pathogens (Rogers & Eastland, 2021). The detection of the pathogen such as GAS causes a biochemical cascade that causes mast cell degeneration which activates inflammatory response (Chauhan et al., 2016). The releases histamine, production of IgE, and activates chemotactic factors that attract neutrophils, basophils, dendritic cells, monocytes, prostaglandins, leukotrienes, and platelet (Marshall et al., 2018). Moreover, the vasodilation in the endothelium of the blood vessels leads to an increase in capillary permeability that circulates platelets, leukocytes, and plasma proteins (Marshall et al., 2018).

How another characteristic (e.g., gender, genetics) would change your response

There are many factors that can contribute to the risk of acquiring an infectious disease. Among several factors age, individual-specific immunity response, stress, and nutrition can influence the way the individual reacts to the pathogens. Furthermore, the virulence factor and antimicrobial resistance mechanism of the GAS also influence the immune response in the individual (Khosravi et al., 2016).   Especially children are more prone to getting strep throat due to underlying genetic and immunologic susceptibility to infections. Therefore, early detection, diagnosis, and the right treatment are essential to prevent the spread and colonization of the pathogens and preventing adverse events.

References

Chauhan, S., Kashyap, N., Kanga, A., Thakur, K., Sood, A., & Chandel, L. (2016). Genetic diversity among group A Streptococcus isolated from throats of healthy and Symptomatic children. Journal of Tropical Pediatrics, 62(2), 152–157. https://doi.org/10.1093/tropej/fmv092

Khosravi, A. D., Ebrahimifard, N., Shamsizadeh, A., & Shoja, S. (2016). Isolation of Streptococcus pyogenes from children with pharyngitis and emm type analysis. Journal of the Chinese Medical Association, 79(5), 276–280. https://doi.org/10.1016/j.jcma.2016.01.002

Marshall, J. S., Warrington, R., Watson, W., & Kim, H. L. (2018). An introduction to immunology and immunopathology. Allergy, Asthma & Clinical Immunology, 14(S2). https://doi.org/10.1186/s13223-018-0278-1

Miguel-Rodriquez, A. S., Armentia, A., Martin-Armentia, S., Martin-Armentia, B., Estevan, M. C. L., & Peinado, I. I. (2018). Importance of allergic hypersensitivity to medications. International Journal of Allergy Medications, 4(2). https://doi.org/10.23937/2572-3308.1510032

Rogers, J., & Eastland, T. (2021). Understanding the most commonly billed diagnoses in primary care. The Nurse Practitioner, 46(5), 48–54. https://doi.org/10.1097/01.npr.0000742908.69893.bb

This paper is a case study involving a 27-year-old patient with a history of substance abuse who is found unresponsive by emergency medical services. The patient becomes responsive after being administered naloxone. The essay examines the role of genetics, reasons for patient’s symptoms, physiological response, cells involved, and influence of other characteristics.

Genetics play a role in substance use disorders. For example, opioid use disorder has large risk of being inherited in families. Genes such as OPRM1 variates and A118G also predispose individuals to substance abuse disorder. Individuals of European descent with OPRD1 genes also have high predisposition to opioid use disorder. Additional genes include KCNG2, CNHIH3, KCNC1, RGMA, and APBB2 genes (Crist et al., 2019; Liu et al., 2019).

The patient presented with symptoms such as unresponsiveness due to central nervous system depression by the opiate overdose. The patient became response following the administration of naloxone since its an opiate antagonist that reverses the depressing effects of opiates. The patient reported pain in left hip and forearm because the effects of the opiates had ben reversed, hence, perception of pain. There is also tissue necrosis that may have developed due to poor tissue perfusion from depressed central nervous system, which affected circulation and respiratory system (Parthvi et al., 2019). The patient also developed respiratory acidosis, which increased serum potassium, hence, hyperkalemia and ECG changes.

The cells involved in the patient’s symptoms include mast cells, neutrophils, and macrophages. These cells induce the induction and transition of the pain the patient experience. Adaptive immune cells such as B and T cells also initiate and resolve pain. Characteristics such as age would change my response in this case study (Machelska & Celik, 2020). For example, the elderly patients have low sensitivity to pain stimuli and potentially worse outcomes due to opiate overdose. These changes will affect the treatment interventions.

In summary, substance abuse has genetic predisposition. The patient developed the given symptoms because of the effects of opioid overdose and naloxone. Age would affect the clinical symptoms and management of opiate overdose.

 

 

References

Crist, R. C., Reiner, B. C., & Berrettini, W. H. (2019). A review of opioid addiction genetics. Current Opinion in Psychology, 27, 31–35. https://doi.org/10.1016/j.copsyc.2018.07.014

Liu, M., Jiang, Y., Wedow, R., Li, Y., Brazel, D. M., Chen, F., Datta, G., Davila-Velderrain, J., McGuire, D., Tian, C., Zhan, X., Choquet, H., Docherty, A. R., Faul, J. D., Foerster, J. R., Fritsche, L. G., Gabrielsen, M. E., Gordon, S. D., Haessler, J., … Vrieze, S. (2019). Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nature Genetics, 51(2), Article 2. https://doi.org/10.1038/s41588-018-0307-5

Machelska, H., & Celik, M. Ö. (2020). Opioid Receptors in Immune and Glial Cells—Implications for Pain Control. Frontiers in Immunology, 11. https://www.frontiersin.org/articles/10.3389/fimmu.2020.00300

Parthvi, R., Agrawal, A., Khanijo, S., Tsegaye, A., & Talwar, A. (2019). Acute Opiate Overdose: An Update on Management Strategies in Emergency Department and Critical Care Unit. American Journal of Therapeutics, 26(3), e380. https://doi.org/10.1097/MJT.0000000000000681

NURS 6501 Week 1 Discussion: Alterations in Cellular Processes Sample Essay A 16-year-old boy comes to clinic with chief complaint of sore throat for 3 days. Denies fever or chills. PMH negative for recurrent colds, influenza, ear infections or pneumonias. NKDA or food allergies. Physical exam reveals temp of 99.6 F, pulse 78 and regular with respirations of 18. HEENT normal with exception of reddened posterior pharynx with white exudate on tonsils that are enlarged to 3+. Positive anterior and posterior cervical adenopathy.

Rapid strep test performed in office was positive. His HCP wrote a prescription for amoxicillin 500 mg po q 12 hours x 10 days disp #20. He took the first capsule when he got home and immediately complained of swelling of his tongue and lips, difficulty breathing with audible wheezing. 911 was called and he was taken to the hospital, where he received emergency treatment for his allergic reaction.

Overview of diagnoses and genetics

Streptococcus pyogenes or strep throat is an acute bacterial infection that affects the oropharynx and nasopharynx. Strep throat presents as a sore throat, pain while swallowing, and a fever. Patients may also experience a headache, nausea, vomiting, or abdominal pain. The average incubation period is 1-4 days. The highest risk of transmission occurs during the acute stage when a patient coughs or sneezes. If untreated, patients may experience an acute rheumatic fever or glomerulonephritis (Al-Dewan, Al Saadi & Ali, 2020). This patient was treated with amoxicillin, a type of penicillin. The patient subsequently had an allergic reaction to the amoxicillin. While strep throat does not have a genetic component, a penicillin allergy does. Patients who have reported penicillin allergies can have a genetic variation on an immune system gene called HLA-B. Some patient’s HLA genes have been linked to bad reactions of specific drugs. The patients are predisposed to have a higher risk of allergic drug reactions (Erdmann, 2020).

Patient presentation and physiologic response

The patient is presenting with symptoms of low-grade fever, reddened posterior pharynx with white exudate, 3+ tonsils, and enlarged cervical lymph nodes. These are symptoms of strep throat. The patient is presenting this way because he contracted bacteria through the mucus membranes and the infection invaded, multiplied, and disseminated. The patient had an unknown and underlying drug allergy to penicillin; therefore, he had an allergic reaction to penicillin. The patient had a type 1 or beginning of an anaphylactic reaction. IgE antibodies were produced in response to the medication components.

These antibodies (IgE) bind to mast cells and basophils, which contain histamine granules that are released in the reaction and cause inflammation (Justiz-Vaillant & Zito, 2019). The cells involved in this process are eosinophils, mast cells, and basophils. The patient may have had a genetic predisposition to allergies as if his parents had an anaphylactic allergic response to penicillins then a provider may be cautious to prescribe penicillin as well.

References

Al-Dewan, H. A., Al Saadi, K. A., & Ali, H. H. M. (2020). Role of superantigen A gene on some immunological markers in the streptococcal pharyngitis patients. EurAsian Journal of Biosciences14(2), 7603–7612.

Erdmann, J. (2020). Penicillin allergies may be linked to one immune system gene. Science News. https://www.sciencenews.org/article/penicillin-allergies-immune-system-genetics. 

Justiz-Vaillant, A. A., & Zito, P. M. (2019). Immediate hypersensitivity reactions. In Stat-Pearls. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK513315/

NURS 6501

Scenario 1: A 16-year-old boy comes to clinic with chief complaint of sore throat for 3 days. Denies fever or chills. PMH negative for recurrent colds, influenza, ear infections or pneumonias. NKDA or food allergies. Physical exam reveals temp of 99.6 F, pulse 78 and regular with respirations of 18. HEENT normal with exception of reddened posterior pharynx with white exudate on tonsils that are enlarged to 3+. Positive anterior and posterior cervical adenopathy. Rapid strep test performed in office was positive. His HCP wrote a prescription for amoxicillin 500 mg po q 12 hours x 10 days disp #20. He took the first capsule when he got home and immediately complained of swelling of his tongue and lips, difficulty breathing with audible wheezing. 911 was called and he was taken to the hospital, where he received emergency treatment for his allergic reaction.

Post an explanation of the disease highlighted in the scenario you were provided. Include the following in your explanation:  I suggest that each bullet point be a subject heading and submit in APA format.  Each bullet point should reflect a subject heading followed by subsequent content reflective of primary source(s) of reference published within the last 6 years.

  • The role genetics plays in the disease.
  • Why the patient is presenting with the specific symptoms described.
  • The physiologic response to the stimulus presented in the scenario and why you think this response occurred.
  • The cells that are involved in this process.
  • How another characteristic (e.g., gender, genetics) would change your response.

The role genetics plays in the disease

Technology advancement has caused a tremendous change in molecular genetics, this leads to next-generation sequencing strategies that are increasingly used in the causal variants associated with allergic diseases. The pervasiveness of allergic traits in connection to family history has demonstrated a gradual increase in the risk of developing asthma as shown in many studies, AR, or AD with the presence of one or both parents with allergic disease. It is also greater than three times if allergic disease occurred in more than first-degree relative. To this day despite technological progress, family history remains one of the most reliable tools for the prognosis of allergic disease (Ortiz & Barnes, 2015).

Our molecular understanding of anaphylaxis is that it is an IgE/mast cell/basophil-mediated event (Galli, 2005). There are many experimental data over the years supporting this data in defining the antibody of allergy as the immunoglobulin IgE, then the cloning of the FcεR receptors and demonstrating their presence on mast cells, along with the recognition of mast cell products as having direct vascular effects that can lead to hypotension and shock, which characterizes severe anaphylaxis (Oettgen, 2016). Also, other mast cell products may contribute to allergy and anaphylaxis, including proteoglycans, serine proteases, lipid-derived mediators, cytokines, and platelet-activating factor (PAF) (Galli, 2005).

Why the patient is presenting with the specific symptoms described

The presenting symptoms may be related to strep throat or Streptococcal Pharyngitis which is an infection of the back of the throat including the tonsils caused by group A streptococcus (GAS). Since the signs and symptoms of streptococcal pharyngitis and non-streptococcal pharyngitis overlap broadly, the best approach is a laboratory test to determine whether group A streptococci are present in the pharynx (Oliver et al., 2018). It may be either a throat culture or a rapid antigen detection test (RADT) that can detect the presence of group A streptococcal carbohydrate on a throat swab. For a patient having the signs and symptoms of acute pharyngitis, a positive throat culture or RADT can establish the diagnosis of strep throat. However, the RADT being less sensitive compared to throat cultures, a negative RADT should be confirmed with the results of a throat culture. Signs of an Anaphylaxis Shock appear immediately after the patient is given an oral dose of Amoxicillin 500mg (Peter, 1992).

The physiologic response to the stimulus presented in the scenario and why you think this response occurred

After the patient took the prescribed Amoxicillin (Penicillin) 500 mg, he started displaying signs and symptoms of Anaphylaxis Shock. Adverse drug reactions are the leading cause of medical injury in hospitalized patients in the United States. The number of patients affected is four times higher compared to the number of people killed in motor vehicle accidents every year (Craig & Mende, 2019).  Antibiotics, where penicillin comprise the largest class in this group, account for about 15% to 30% of the drug expenditure in the world (Blanca, 1995). So, it is not a surprise that antibiotics often trigger allergic and anaphylactic reactions. The incidence of penicillin reactions is presumed to be between 1% and 10% as there is no exact estimate to be reached due to subjective and non-standardized criteria (Craig & Mende, 1999). Those who have taken antibiotics without problems have less than a 1% risk of an allergic incident when rechallenged (Weiss & Adkinson, 1988). Penicillin’s adverse reactions can be up to 10% and are life-threatening because of bronchospasm, laryngeal edema, or hypotension. Two percent to ten percent of these incidents proved to be fatal. Also, it was found out that patients with no history of allergy suffer the most serious reactions (Boguniewicz, 1995).

The cells that are involved in the process

After the patient took the prescribed Amoxicillin 500mg orally, he started to have an inflammatory response to it. The immediate symptoms show an Anaphylaxis shock. Systemic anaphylaxis is generally recognized as a severe allergic reaction caused by IgE-mediated activation of mast cells, leading to a massive release of vasoactive mediators that induce acute hypotension and shock. Anaphylaxis is an acute, multisystem, severe type I hypersensitivity reaction that develops in minutes to hours following antigen exposure (Galli, 2005). If the allergy is mild, the results are wheezing, rashes, and some gastrointestinal signs like bloating or cramping. If it is severe, the patient develops bronchoconstriction with hypoventilation, cardiac dysrhythmias, systemic vasodilation, and central nervous system abnormalities. Anaphylaxis most often occurs in patients in response to some medications like amoxicillin 500 mg in this case. Others are those with severe allergies to specific foods like shellfish, nuts, and milk products and to insect stings, specifically the Hymenoptera venom. In the US, more than 1,500 deaths per year are attributed to acute hypersensitivity reactions (Neugut et al., 2001).

How another characteristic (e.g., gender, genetics) would change your response.

Back in the day, evidence-based practice has focused on the work of Gregor Mendel where disease interventions were based on the expression of a single locus disorder with simple genetically attributed causes (Frazier et al., 2015). Now, the recent advances in the field of etiology for the genetic composition of disease expression and evolution have incorporated relationships between genetic health, genetic risk, and intervention. Diseases are now studied and treated involving multifactorial causes. Complex diseases which include extreme individual variation are now a public health concern. Therefore, there are genetic components with vulnerable alleles that if combined with the right triggers may start or aggravate a disease (Frazier et al., 2015). In conclusion, genetic disease expression and evolution are multifaceted. It can be affected by the lifestyle of the individual which includes food preferences, occupation, choice of residence, and the personal behaviors that said individual chooses to engage in (Frazier et al., 2015).

References:

Blanca, M. (1995). Allergic reactions to penicillins. A changing world?. Allergy, 50(10), 777-782.

Boguniewicz, M. (1995). Adverse reactions to antibiotics: is the patient really allergic?. Drug safety, 13(5), 273-280.

Craig, T. J., & Mende, C. (1999). Common allergic and allergic-like reactions to medications: when the cure becomes the curse. Postgraduate medicine, 105(3), 173-181.

Frazier, L., Menininger, J., Lea, D., Boerwinkle, E. (2015). Genetic discoveries and nursing implications for complex disease prevention and management. Journal of Professional Nursing, 20(4), 222-229.

Galli, S. J. (2005). Pathogenesis and management of anaphylaxis: current status and future challenges. Journal of Allergy and Clinical Immunology, 115(3), 571.

Neugut, A. I., Ghatak, A. T., & Miller, R. L. (2001). Anaphylaxis in the United States: an investigation into its epidemiology. Archives of internal medicine, 161(1), 15-21.

Oettgen, H. C. (2016). Fifty years later: emerging functions of IgE antibodies in host defense, immune regulation, and allergic diseases. Journal of Allergy and Clinical Immunology, 137(6), 1631-1645.

Oliver, J., Wadu, E. M., Pierse, N., Moreland, N. J., Williamson, D. A., & Baker, M. G. (2018). Group A Streptococcus pharyngitis and pharyngeal carriage: a meta-analysis. PLoS neglected tropical diseases, 12(3), e0006335.

Ortiz, R. A., & Barnes, K. C. (2015). Genetics of allergic diseases. Immunology and Allergy Clinics, 35(1), 19-44.

Peter, G. (1992). Streptococcal pharyngitis: current therapy and criteria for evaluation of new agents. Clinical infectious diseases, 14(Supplement_2), S218-S223.

Weiss, M. E., & Adkinson, N. F. (1988). Immediate hypersensitivity reactions to penicillin and related antibiotics. Clinical & Experimental Allergy, 18(6), 515-540.

Scenario 2: A mother brings her 6-month-old daughter to the HCP for evaluation of possible colic. The mother says the baby has had many episodes of crying after eating and, despite having a good appetite, is not gaining weight. The mother says the baby’s belly “gets all swollen sometimes.” The mother says the baby tastes “salty” when the mother kisses the baby. Further workup reveals a diagnosis of cystic fibrosis. The mother relates that her 23-month-old son has had multiple episodes of “chest congestion” and was hospitalized once for pneumonia. The mother wants to know what cystic fibrosis is, and she also wants to know if she should have any more children.

As mentioned in this scenario, the work up on the 6-month-old little girl revealed a diagnosis of cystic fibrosis. Cystic fibrosis (CF) is an inherited genetic disorder that causes severe damage to the lungs, digestive system, and other organs in the body (“Cystic fibrosis – Symptoms, and causes,” 2020).

CF affects about 35,000 people in the United States (“Cystic fibrosis,” 2020). CF is prevalent in 1 in every 2500 Caucasian live births and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (Kelsey et al., 2019, p. xx). CFTR is a large protein of more than 1400 amino acids separated into 2 homologous halves, each containing 6 membrane-spanning segments and a nucleotide-binding domain (Kelsey et al., 2019, p. xx). This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The channel transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary to produce thin, freely flowing mucus (“CFTR gene: MedlinePlus genetics,” n.d.). For those with CF, salt cannot move as it normally does through the cells that line the sweat duct (Editorial Team, 2019). Salt is then excreted in the sweat and explains why the baby tasted salty when her mother kissed her.

Every person has two copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A person must inherit two copies of the CFTR gene that contain mutations — one copy from each parent — to have cystic fibrosis (“CF genetics: The basics,” n.d.). A person must have a mutation in both copies of the CFTR gene to have CF. If someone has a mutation in only one copy of the CFTR gene and the other copy is normal, he or she does not have CF and is a CF carrier. About 10 million people in the United States are CF carriers. CF carriers can pass their copy of the CFTR gene mutation to their children. Each time two CF carriers have a child together, the chances are 25 percent (1 in 4) the child will have CF, 50 percent (1 in 2) the child will be a carrier but will not have CF, 25 percent (1 in 4) the child will not be a carrier of the gene and will not have CF (“CF genetics: The basics,” n.d.). So, I would discuss with the mother that if she chooses to have another child with someone who also has the CF gene, there is a 1-in-4 (25%) chance that the baby will CF.

Cystic fibrosis affects the intestines, pancreas, and liver. Because the digestive fluids are thicker in those with CF, this can block the intestines and cause constipation and abdominal discomfort. This can also lead to an obstruction. Some affected babies have meconium ileus, a blockage of the intestine that occurs shortly after birth (“Cystic fibrosis: MedlinePlus genetics,” n.d.). When ducts in the liver cannot drain, the bile ducts can become blocked, which will lead to inflammation of the liver and, in this case, swelling of the baby’s abdomen. When the thick mucus blocks the ducts within the pancreas, the enzymes in food are not able to be broken down to reach the small intestines to break down food and absorb nutrients leading to an inability to gain weight (“cause and impact of cystic fibrosis (CF),” n.d.).

The Her mother mentioned that her 23-month-old son has had multiple chest

congestion episodes and was hospitalized once for pneumonia. Most people with CF are diagnosed by age 2 thanks to newborn screening tests (“Role of genetics in CF,” n.d.). It is my guess that he may have allergies, asthma or he may go to daycare where he is exposed to other children with colds that contribute to these episodes and hospitalization.

References

CF genetics: The basics. (n.d.). Cystic Fibrosis Foundation | CF Foundation. https://www.cff.org/What-is-CF/Genetics/CF-Genetics-The-Basics/

Cystic fibrosis – symptoms, and causes. (2020, March 14). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700

Cystic fibrosis. (2020, June 29). https://www.cdc.gov/genomics/disease/cystic_fibrosis.htm

Cystic fibrosis: MedlinePlus genetics. (n.d.). MedlinePlus – Health Information from the National Library of Medicine. https://medlineplus.gov/genetics/condition/cystic-fibrosis/

Editorial Team. (2019, August 16). Salty skin and sweat. Cystic-Fibrosis.com. https://cystic-fibrosis.com/symptoms/salty-skin

Kelsey, R., Manderson Koivula, F. N., McClenaghan, N. H., & Kelly, C. (2019). Cystic fibrosis-related diabetes: Pathophysiology and therapeutic challenges. Clinical Medicine Insights: Endocrinology and Diabetes12, 117955141985177. https://doi.org/10.1177/1179551419851770

Role of genetics in CF. (n.d.). Cystic Fibrosis Foundation | CF Foundation. https://www.cff.org/What-is-CF/Role-of-Genetics-in-CF/

The cause and impact of cystic fibrosis (CF). (n.d.). CFSource. https://www.cfsource.com/understanding-the-impact?gclid=03f509e1bb3716beb8b869de7a6b3f2b&gclsrc=3p.ds&&Specific+Content%5BMULTI-IM/BO%5D+pancreas%2Bpancreas+%2Bcystic+%2Bfibrosis&msclkid=03f509e1bb3716beb8b869de7a6b3f2b&utm_source=bing&utm_medium=cpc&utm_campaign=Specific%20Content&utm_term=%2Bpancreas%20%2Bcystic%20%2Bfibrosis&utm_content=%5BMULTI-IM%2FBO%5D%20pancreas#digestive-system-impact

What is cystic fibrosis? 9 symptoms to be aware of. (2021, January 4). Entirely Health. https://entirelyhealth.com/conditions/cystic-fibrosis/what-is-cystic-fibrosis-9-symptoms-to-be-aware-of/

Purpose Statement

This paper is being written to explain the pathology of cystic fibrosis. I personally have a friend who has this disease and have learned from her. The topics that will be covered are, how cystic fibrosis is created at a cellular level, genetics role in cystic fibrosis, the reasoning for the symptoms that the patient presented with, the description of the cells involved in cystic fibrosis, and how other characteristics would change the child’s response to cystic fibrosis. In short what I remember from nursing school is that cystic fibrosis is a genetic disorder which is an autosomal recessive gene that is carried by both the mother and the father. The abnormality occurs in chromosome 7 which is where creates an inability to transport small molecules across the cell’s membrane, which in turn, dehydrates the cells of the epithelium and this then creates dry secretion. This is a broad overview of what this disease is, but I will go into further detail below.

 The Role Genetics Plays in the Disease

Genetics play an important role in this disease, according to an article published in PubMed titled Cystic fibrosis genetics: from molecular understanding to clinical application states that due to a defective epithelial cell that is defective, this cell is inherited and is an autosomal recessive gene. The genetic information that is in the cell, which is the recipe for the cell to make proteins (Cutting, 2015).  According to Pathophysiology of disease: An introduction to clinical medicine, if a person receives a cystic fibrosis transmembrane conductance regulator gene (CFTCR), or a person can receive two copies of the CFTCR gene.

This copy has a mutation of the cystic fibrosis gene, furthermore these two copies of the CFTR gene have stored a mutation which is the on chromosome seven. So, when the recipe is being presented to the cell to be made, the genetic information is then stored into the deoxyribonucleic acid which is known as DNA.  This is part of the twenty-three pairs of chromosomes, but on the seventh chromosome, the cystic fibrosis recipe is stored in that chromosome. In the DNA, where the CFTCR gene recipe lives, if there is one copy of the recipe than the gene will not show up in the person but will be a carrier but if there are two copies of the recipe being stored in the chromosome than the cystic fibrosis gene than the person will have cystic fibrosis (McCance at el., 2019).

 Why the Patient is Presenting with the Specific Symptoms Described

The symptoms that the baby presented with were salty skin, periodically patient gets a swollen stomach, and not gaining weight normally. According to an article published Journal of Cystic Fibrosis, titled Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy, the major organ systems that are made up of epithelia. The systems that are being affected in this patient are the sweat glands, liver’s bile duct, and intestines in the gastrointestinal tract. The article goes on to explain that the loss of pancreatic function leads to the patient suffering from malnutrition, and not growing normally. Therefore, the replacement of enzymes is important for this patient to be able to prevent the clogging of the cell because of the inability to breakdown an access amount key nutrient (Cutting, 2015).

The physiologic response to the stimulus presented in the scenario and why you think this response occurred

After reading different sources, I was able to breakdown the pathology behind this patient’s symptoms. This disease starts with the CFTR gene protein being mutated in the chromosome seven, which there are two copies of the recipe, this mutation causes the decrease of chloride acceptance and ion being transported, then this makes the absorption of water to increase which throws off ciliary from completing the job and there is mucus that is dry, this is what causes the skin to be salty of the baby. The stomach inflammation and swelling that is being experienced, is due to the CFTR gene protein not having the right recipe present to the epithelial cell, this is causing malfunction by changing the reabsorption of the sodium, chloride and potassium in the cell, the recipe tells the cell to keep the sodium, chloride and potassium outside of the cell, this causes a back-up of outside of the cell structure and blocks the cell from absorbing the nutrients especially, proteins, fats and vitamins that are fat soluble.

The Cells that are Involved in this Process

The cells that are involved in this process start with the epithelial membranes which are present in the digestive tract, pancreas, airways, and reproductive area. According to an article in Apoptosis Journal, stated that cystic fibrosis is a caused by the dysfunction in the epithelial cell which leads to inflammation and an inability to create homeostasis because of the constant inflammation caused by the CFTR gene. Furthermore, the epithelial cells end up failing and create apoptosis in the epithelial cell because of the inflammation the is created in the endoplasmic reticulum (Soleti at el., 2013).

How another characteristic (e.g., gender, genetics) would change your response

For cystic fibrosis, it is important to understand that this would not be a disease if the parents did not carry the gene. The gene is the CFTR gene mutation, mentioned throughout this paper. According to a study done by Harvard Stem Cell Institute, where a lung cell was isolated to examine the function of the CFTR gene. It was shown in the study that if the ionocytes in the cell are not doing their job because it is expressing CFTR gene in increased levels, then the symptoms are created in the cell (Montoro at el., 2018). This occurs in the form of thick mucus and creates the response in the body that does not allow for the patient to regulate sodium, chloride, and potassium in a normal fashion.

Conclusion

During this journey of studying disease in depth and truly understanding how they work will help in the future of my career. I believe that if screening done at the hospitals before they leave would be beneficial. When parents are informed about the possibility of something occurring and what it means, parents will be empowered and get treatment before or if cystic fibrosis symptoms could show up. Also, encouraging parents to come to their baby checkups, will also allow for the medical staff to ask the right questions and treat the baby early, if they see symptoms. Cystic fibrosis is a challenge some patients may struggle with and it is our job as practitioners to catch things before extreme measures need to be taken.

References

Cantin, A.M, Hartl, D, Konstan, M and Chmiel, J. (2015). Inflammation in Cystic Fibrosis Lung Disease and Therapy. Journal of                        Cystic Fibrosis. Retrieved from https://www.cysticfibrosisjournal.com/article/S1569-1993(15)00058-2/fulltext.

Cutting G. R. (2015). Cystic fibrosis genetics: from molecular understanding to clinical application. Nature reviews.                                        Genetics16(1), 45–56. https://doi.org/10.1038/nrg3849

McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). St.                           Louis, MO: Mosby/Elsevier.

Montoro D.T., Haber A.L., Biton M. et at. (2018) A Revised Airway Epithlial Heiracrchy Inclues CFTR-Expressing                                             Inoncytes.Nature. DOI: 10.1038/s41586-018-0393-7

Soleti, R., Porro, C., & Martínez, M. C. (2013). Apoptotic process in cystic fibrosis cells. Apoptosis : an                   international journal on programmed cell death18

Patients with CF have a defective CFTR protein that is unable to transport chloride (an element in salt) to the cell surface (Cystic Fibrosis Foundation, n.d.). When salt cannot move through the cells as it normally should, higher amounts of salt are found on the skin resulting in a salty taste (Cystic Fibrosis Foundation, n.d.). Salt and water typically travel together through the body, but in CF this balance in the cells is disrupted and there is a lack of water due to the defective CFTR protein which causes thick and sticky secretions in the affected organs.

The baby’s bloating is caused by these thickened secretions that can block the ducts in the pancreas and cause irregular bowel movements, pain, cramping, and even intestinal blockages (Cystic Fibrosis Foundation, n.d.). When the pancreas has obstructed ducts, it prevents the movement of pancreatic enzymes through the digestive tract which causes problems with the absorption of needed nutrients for proper growth of the baby (McCance & Huether, 2019).

Physiologic Response to Stimulus

The pancreatic ducts get clogged by the thicker secretions and this causes a decrease in the digestive enzymes that are secreted by the pancreas. When there are not enough digestive enzymes to properly break down the food, there is a problem absorbing nutrients needed for proper growth such as fats, proteins, and fat-soluble vitamins such as A, D, E, and K (Cystic Fibrosis Foundation, n.d.). Incomplete digestion leads to bloating, cramping, diarrhea, vitamin deficiency, and difficulty gaining weight.

Involved Cells

Epithelial cells are largely responsible for ion and fluid absorption and secretion (Saint-Criq, & Gray, 2017). In patients with CFTR protein defects, there are problems with sodium, chloride, and water absorption and secretion. The chloride can not be transported correctly which causes an imbalance between the electrolytes and water and ultimately leads to thickened secretions that cause problems throughout the organs.

Other Characteristics

More information is needed related to race, as Caucasians have a higher risk of developing CF, and African Americans, Asians, and Hispanics have a lower risk (Cystic Fibrosis Foundation, n.d.). Having a sibling, cousin, or other close family members also increases the risk of CF (Cystic Fibrosis Foundation, n.d.). In this scenario, it seems the older sibling may also have CF, but further testing is needed for proper diagnosis.

References

Cystic Fibrosis. (n.d.). CDC.  https://www.cdc.gov/genomics/disease/cystic_fibrosis.htm.

Cystic fibrosis – Symptoms and causes – Mayo Clinic. (2021).  https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700.

McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.).

Saint-Criq, V., & Gray, M. A. (2017). Role of CFTR in epithelial physiology. Cellular and molecular life sciences: CMLS74(1), 93–115. https://doi.org/10.1007/s00018-016-2391-y

it is true that cells are the basic structural components of the body and are specialized to conduct different functions in the body. The central dogma also illustrates the pivotal role of genes in dictating the specialization of cells and subsequent events. Disease can alter the nature of cells thereby interfering with the normal cell functions. I find your case analysis quite intriguing, there are many patients who complain of sore throat that is related to allergic conditions and your analysis through genetic involvement is informative (Centers for Disease Control and Prevention,2021).

Group A streptococcus pharyngitis among children and adolescents is common and the identification of the genes associated with the common occurrence provides an avenue for solving the menace. Hypersensitivity relation to genetic composition also provides a better understanding of the recurrence of such cases (McCance & Huether, 2019). I also think that the bod defense system is triggered by recognition of the pathogen and the process of acting against the identified antigen leads to the symptoms, which include inflammation that would be felt as sore throat.

I agree hat the physiological processes upon identification of the antigen includes a variety of cells mediators that take part in the inflammatory pathway. These processes cause heat, swelling and redness. The patient characteristics that define different responses include age as age relates to immunity. Children are more susceptible to some diseases as compared to adults. Elderly people are also prone to some diseases that are not so common among young adults. Allergy to drugs also links to age as the allergy increases with age (Soderholm et al., 2018). I concur with you that severe allergic reaction would definitely be a concern

References

Soderholm, A. T., Barnett, T. C., Sweet, M. J., & Walker, M. J. (2018). Group A streptococcal

pharyngitis: Immune responses involved in bacterial clearance and GAS‐associated immunopathology. Journal of leukocyte biology, 103(2), 193-213.

McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in

adults and children (8th ed.). Mosby/Elsevier.

Centers for Disease Control and Prevention. (2021, November 23). Pharyngitis (strep throat): Information for clinicians. Retrieved March 1, 2022, from https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html

Kidney transplant is an effective treatment for patients suffering from end-stage renal disease. However, some patients develop adverse effects including kidney rejection. The management of kidney transplant rejection depends on the type and patient factors. Therefore, this paper examines why a patient with acute kidney transplant developed the described symptoms, genes associated with kidney transplant rejection and process of immunosuppression.

Why the Patient Presented the Symptoms Described

The patient presented symptoms that include gaining weight, decreased urinary output, fatigue, and running temperatures up to 101 F. The patient gained weight because of the increased body fluid volume level. The kidneys excrete excess fluids from the body. Impaired kidney function as seen in the case study affects the regulation of fluids in the body, hence, its accumulation and weight gain. The decline in renal function also impaired normal urine output. This led to reduced urine production, as seen in the case study. The rejection altered the normal renal function in the excretion process, leading to oliguria. The kidneys also eliminate toxins from the body. This includes excess ammonia in urine. Impaired kidney problems affect the elimination of these toxins, which lead to symptoms such as fatigue, poor concentration, acidosis, and anemia. Therefore, this explains the patient’s experience of fatigue. Patients with end-stage renal disease and those with kidney transplant rejection problems also experience immunosuppression (Rauen et al., 2020). This predisposes them to infections, hence, the fever that the patient has.

Genes Associated with the Development of the Disease

Genes have been linked with kidney transplant rejection. They include cytochrome p450 2EI (CYP2EI), CYP3A5, cytotoxic T-lymphocyte associated protein 4 (CTLA4), C-X-C motif chemokine ligand 8 (CXL8), epoxy hydrolase 2, coagulation factor II thrombin, and coagulation factor V genes. In addition, Forkhead box P3, Fc fragment of IgG receptor IIA, major histocompatibility complex class II, I, DO alpha, and interleukin 1 beta, 2, 2-receptor subunit beta genes also play a role in the development of the rejection in kidney transplant. Genes such as interleukin genes are inflammatory cytokines that inhibits inflammatory processes once a person received an allograft. On the other hand, this gene also downgrades the maturation of antigens and cells that develops host’s immunity following the transplant (Arnold et al., 2022; Spicer & Runkel, 2019; van Vugt et al., 2022). Other genes such as ATP-binding genes increase the body’s resistance towards drugs used in suppressing the immune system following the transplant.

Process of Immunosuppression

Immunosuppression refers to the state in which the ability of the body to fight infections is reduced. The immune system is lowered to a level that it cannot counteract any disease causing organisms from invading the body. The causes of immunosuppression include the use of medications that are used in conditions such as cancer. The other cause is conditions that depress the immune system such as cancer and HIV. Treatments for cancer such as radiotherapy and chemotherapy also cause immunosuppression. The effects of immunosuppression are varied. They include increasing the vulnerability of patients to infections. It also increases costs that patients incur due to frequent hospitalizations (Gupta et al., 2021). Prolonged infections also affect the patients’ quality of life. Patients may also die in cases where the immune system is severely compromised.

Conclusion

In conclusion, the patient presented the symptoms because of reduced renal functioning. Genes are involved in the development of kidney transplant rejection. The rejection may result in immunosuppression, which has negative effects on health.

References

Arnold, M.-L., Heinemann, F. M., Oesterreich, S., Wilde, B., Gäckler, A., Goldblatt, D., Spriewald, B. M., Horn, P. A., Witzke, O., & Lindemann, M. (2022). Correlation of Fc Receptor Polymorphisms with Pneumococcal Antibodies in Vaccinated Kidney Transplant Recipients. Vaccines, 10(5), Article 5. https://doi.org/10.3390/vaccines10050725

Gupta, R., Woo, K., & Yi, J. A. (2021). Epidemiology of end-stage kidney disease. Seminars in Vascular Surgery, 34(1), 71–78. https://doi.org/10.1053/j.semvascsurg.2021.02.010

Rauen, T., Wied, S., Fitzner, C., Eitner, F., Sommerer, C., Zeier, M., Otte, B., Panzer, U., Budde, K., Benck, U., Mertens, P. R., Kuhlmann, U., Witzke, O., Gross, O., Vielhauer, V., Mann, J. F. E., Hilgers, R.-D., Floege, J., Floege, J., … Hilgers, R.-D. (2020). After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy. Kidney International, 98(4), 1044–1052. https://doi.org/10.1016/j.kint.2020.04.046

Spicer, P., & Runkel, L. (2019). Costimulatory pathway targets for autoimmune and inflammatory conditions: Clinical successes, failures, and hope for the future. Expert Opinion on Investigational Drugs, 28(2), 99–106. https://doi.org/10.1080/13543784.2019.1557146

van Vugt, L. K., Schagen, M. R., de Weerd, A., Reinders, M. E., de Winter, B. C., & Hesselink, D. A. (2022). Investigational drugs for the treatment of kidney transplant rejection. Expert Opinion on Investigational Drugs, 31(10), 1087–1100. https://doi.org/10.1080/13543784.2022.2130751

I agree with your post on strep A and found it interesting that females are most likely to have drug-induced anaphylaxis. There is not much research on how it is more frequent in females. Adult females are also more likely to have drug-induced anaphylaxis, but no clear sex predominance has been reported in fatal or severe drug-induced anaphylaxis. “Possible explanations for female predisposition to drug allergy are multifactorial and include disproportionate utilization of health care with more exposure to antibiotics or medications, genetic factors related to the X chromosome, epigenetic changes, and discrepant hormonal interactions with immune cells” (Eaddy & Broyles, 2019). So, the research on that is still ongoing. Other than females being more likely to have anaphylaxis, your explanation still does not make physiological sense. I only say that because this post is about a 16-year-old boy and what he experienced. With Strep A, the bacteria in the body cause many symptoms; the main one is throat inflammation (Ashurst, 2022). Since strep A occurs more in children, age would change the response because kids are more likely to get this than adults. As far as his reaction, since he is not allergic to anything, it could be genetics and require further testing.

 

References

Ashurst JV, Edgerley-Gibb L. Streptococcal Pharyngitis. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525997/

Eaddy Norton, A., & Broyles, A. D. (2019). Drug allergy in children and adults. Annals of Allergy, Asthma & Immunology122(2), 148–155. https://doi.org/10.1016/j.anai.2018.11.014

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