Creepy Crawlie Therapy?

Patient Presentation
A pediatrician heard a radio story on the news about using worms to try to treat Crohn’s disease. She also was reading a book at the time where blood letting through cuts in the skin or leeches was a common medical treatment. She thought it was a good time for a quick review of organisms used for medical therapies that usually were thought of as potentially harmful creepy crawlies.

Discussion
Humans are only one species among the multitudes that inhabit the earth. While many species are used by humans for food, clothing or shelter, as a higher evolved organism, humans are particularly aware of other species that move as they could be a potential predator or cause injury. This wariness is protective, but moving animal species can be domesticated (e.g. dogs, horses), farmed (e.g. cattle, goats) or harvested (e.g. fish, silk) for human use for food, clothing or shelter and also for medicinal use.

Learning Point
Medical leeches have been used since ancient times. The most commonly used leech is Hirudo medicinalis named by Linneaus in 1758. It attaches to the host with a posterior sucker, bites with 3 jaws, and feeds on ~2-20 ml of blood usually within 10-30 minutes. Its saliva has several anticoagulants which allows for continued blood oozing up to 48 hours. It is the oozing effect that is the most useful to help in the treatment of large soft tissue hematomas (e.g. tongue), and especially for venous congestion after surgery for tissue flap reconstructions or reimplantation after amputations. Venous congestion can cause many problems in various surgical repairs and is a common reason for tissue flap failures. Hirudotherapy (or use of medical leeches) is considered an adjuvant after determining that there is not an arterial problem or venous congestion problem that is amenable to further surgery. Hirudotherapy can also be used if additional surgery is contraindicated. Medical leeches are grown specially for medical use. After feeding they are sacrificed in 70% alcohol and disposed of as a biohazard. As the gut of the leech is directly exposed to the patient, prophylactic antibiotics are usually given. The most common leech intestinal flora organism is Aeromonas hydrophilia. The various bioactive anticoagulants in leeches’ saliva and its body are also being researched. While there are several agents, 2 of the more common ones being evaluated are hirudins and hyaluronidase. Hirudins are being invested for antithrombotic effects in venous thrombosis and acute coronary syndromes. Hyaluronidase is being evaluated to increase permeability to improve absorption of fluids.

Helminths or parasite worms are common parasites which in the past affected almost all people. Today they still affect an estimated 2 billion people globally. Helminths appear to have an immunomodulating effect on the human immune system. It is thought that because of helminthic infestations, the human immune system is actively suppressed to allow continued viability of both organisms. Unfortunately, the human host is also less reactive to some other infectious agents such as tuberculosis or malaria and hosts have decreased vaccine responses. The potential advantage for the human host is to be less responsive which can help effects of immune-mediated diseases such as atopy, rheumatoid arthritis, Crohn’s disease, etc.. Pig whipworm, Trichuris suis is one of the most common medically used helminths. There are currently ongoing clinical trials for allergies, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis using helminth-modulated macrophage therapy. Experimental laboratory therapy is also ongoing for diabetes and sepsis. With helminth therapy it is important to note that there is a balance in trying to regulate an individual’s immune system. As one author said: “Because parasitism is on balance detrimental, administration of live helminths is itself a balancing act, attempting to maximize any beneficial effects against a deleterious backdrop. Where the fulcrum of that balance sits will very much vary according to the genetic makeup of the individual.”

While leeches and helminths are creepy crawlies that can be seen, newer research is looking at a much smaller scale. A microbiome are microorganisms that can be commensal, symbiotic or pathogenic and which inhabit our body spaces during health and disease. Common places to have microbiomes are the mouth, gut, vagina, lung and skin. There are many factors which affect an individual’s microbiome including genetics, antibiotics, diet, and environmental exposure (e.g. family, pets, soil, etc.). Studies are providing more information about how the microbiome in prenatal and early life can affect potential disease especially immune-related diseases such as allergies and asthma, inflammatory bowel disease, and also weight gain and obesity and infections. As the science associated with microbiomes is relatively new yet may potentially provide important understanding of normal and disease states, the National Institute of Health has undertaken the Human Microbiome Project as one of several international large scale scientific efforts to better understand human microbiomes.

Questions for Further Discussion
1. What other examples of medical uses of potential harmful species can you think of?
2. What potential side effects do some of these species have?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Parasitic Diseases and Complementary and Integrative Medicine.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Porshinsky BS, Saha S, Grossman MD, Beery I PR, Stawicki SP. Clinical uses of the medicinal leech: a practical review. J Postgrad Med. 2011 Jan-Mar;57(1):65-71.

Zaidi SM, Jameel SS, Zaman F, Jilani S, Sultana A, Khan SA. A systematic overview of the medicinal importance of sanguivorous leeches. Altern Med Rev. 2011 Mar;16(1):59-65.

O’Dempsey T. Leeches–the good, the bad and the wiggly. Paediatr Int Child Health. 2012 Nov;32 Suppl 2:S16-20.

Maizels RM. Parasitic helminth infections and the control of human allergic and autoimmune disorders. Clin Microbiol Infect. 2016 Jun;22(6):481-6.

Steinfelder S, O’Regan NL, Hartmann S. Diplomatic Assistance: Can Helminth-Modulated Macrophages Act as Treatment for Inflammatory Disease? PLoS Pathog. 2016 Apr 21;12(4):e1005480.

Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016 Jul 7;22(7):713-22.

National Institutes of Health. Human Microbiome Project Overview. Available from the Internet at http://commonfund.nih.gov/hmp/overview (rev. 5/16/16, cited 7/19/16).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

Family Meals: They Do Everyone Good

Patient Presentation
An 18-month-old male came to clinic for his health maintenance visit. His dietary history showed he drank ~45 ounces of milk a day mainly from a bottle that he was allowed to have during most of the day. His mother complained that he didn’t eat much solid food, and wouldn’t sit down to eat. She noted that she didn’t really stop to eat herself. She would just drive through a fast-food restaurant and eat in the car even if she was not pressed for time. “It’s just something I do,” she said. He was doing well with normal development. The past medical history showed a healthy male. The social history showed him living with his employed mother. There was maternal family support locally. The family did not receive governmental assistance and the mother felt she had adequate resources from her employment. The pertinent physical exam revealed a smiling male with normal vital signs and growth parameters in the 25-50%. His examination was normal including normal appearing teeth.

The diagnosis of a healthy male with inappropriate food intake and behaviors was made. The pediatrician counseled the mother to decrease the total milk intake to 16 ounces/day and to put this into a sippy-cup or regular cup. “Any other fluid he wants can be up to 4 ounces of juice a day or water. All of it should be in a cup. He also should not be walking around with the cup. If he fills up on fluid he won’t eat. He should have 3 meals and a couple of snacks a day and he needs to sit down whenever he eats or drinks. It really does only take a few minutes and you both can have a nice time together talking and eating. It’s also a good break for you during the day. Even if you do have some fast-food, you should eat it as a family, sitting down together. He’ll learn what is expected of him at the dinner table too.” The laboratory evaluation showed a low hemoglobin and hematocrit so he was started on elemental iron.

The patient’s clinical course at 3 month followup found the mother to be proud of having started some of the interventions. She reported that he was only using a sippy-cup and taking only 24 ounces of milk a day. “He cries so much for the milk that I give him more than I should,” she said. “We are sitting down more together though – at least for dinner and most of his snacks when I am with him. When we are at my mom’s house, we have started to have him sit with us for part of our dinner too,” she remarked.

Discussion
Family meals (FM) are “…occasions when food is eaten simultaneously in the same location by more than 1 family member.” Overall, more frequent family meals are protective for healthy physical and psychosocial functioning across socioeconomic status, race/ethnicity and gender. Why FMs have these protective effects (possibly related to family connectedness) is unclear and additional research is ongoing.

Factors associated with increased FMs include:

  • Increased parental education
  • Gender – adolescent boys report more FM than adolescent females
  • Race/ethnicity – Asian-Americans have more FM than whites who have more than African-Americans. Hispanics have more FMs.
  • Children’s ages – younger children have more FMs than older children and adolescents
  • Parenting style – mothers who are authoritative have more FMs

The ideal FM environment is one that is positive, without arguments if possible and encourages communication among the family members. There should be no television or other electronic devices (including phones) in the room. Quiet music can help to set a positive mood for the meal. FMs do not have to be long and can be as short as 20 minutes.

Barriers to FMs often cited are work and school/extracurricular schedules, lack of meal planning, not having a regular time set for meals, picky eaters, young children not able to sit through the meal, and family members being hungry at different times. Ways to overcome this include setting the expectations that FMs will occur and family members are expected to participate, making grocery lists, making meals ahead of time for use later, and use of time saving devices such as microwave ovens and slow-cookers. Additional ways to keep the FM a popular and daily event include keeping the conversation fun and light, involving the children in meal preparation and serving foods that the children enjoy. FMs also can expand the types of foods children enjoy and the FM should not turn into a short-order restaurant to prepare separate meals for each person’s tastes.

Learning Point
Eating more frequent family meals has better physical and psychosocial outcomes for children including:

  • Increased/Improved
    • Consumption of good nutrition including appropriate calories, “… protein, fiber, calcium, iron, folate, and vitamins A, B-6, B-12, C and E….”, and increased servings of fruits, vegetables, grains and calcium-rich foods.
    • Healthy body weight
    • Body image perception
    • Self-esteem
    • Academic grade point averages, commitment to learning, language skills
    • Family relationships (e.g., perceived family support, communication, and parental involvement), and connectedness
    • Effective communication
  • Decreased
    • Consumption of poor nutrition including soda consumption and saturated fats
    • Disordered eating including less obesity and eating disorders
    • Alcohol and substance abuse (including tobacco and marijuana)
    • Depression and suicidal thoughts
    • Violent behavior

Questions for Further Discussion
1. How often do you personally have family meals?
2. How could you include family meal counseling into your preventative care discussions?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Family Issues and Child Nutrition.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Berge JM, Rowley S, Trofholz A, Hanson C, Rueter M, MacLehose RF, Neumark-Sztainer D. Childhood obesity and interpersonal dynamics during family meals. Pediatrics. 2014 Nov;134(5):923-32.

Martin-Biggers J, Spaccarotella K, Berhaupt-Glickstein A, Hongu N, Worobey J, Byrd-Bredbenner C. Come and get it! A discussion of family mealtime literature and factors affecting obesity risk. Adv Nutr. 2014 May 14;5(3):235-47.

Harrison ME, Norris ML, Obeid N, Fu M, Weinstangel H, Sampson M. Systematic review of the effects of family meal frequency on psychosocial outcomes in youth. Can Fam Physician. 2015 Feb;61(2):e96-106.

DeGrace BW, Foust RE, Sisson SB, Lora KR. Benefits of Family Meals for Children With Special Therapeutic and Behavioral Needs. Am J Occup Ther. 2016 May-Jun;70(3):7003350010p1-6.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

How Common are Herniated Disks in Children?

Patient Presentation
A 15-year-old female came to clinic with a history of lumbar pain for 2 weeks. She was a softball infielder and thought that the pain began after she had increased her training and had to slide into bases over a several day period. She said it was “just always there” and she described 4-6/10 for intensity. No specific movements or position made it worse or better. She had tried using heat and ice, massage and some increased rest at night but she still did not stop playing. Intermittent ibuprofen provided some relief. She denied any specific radiation of the pain into her legs, or bowel or bladder problems. The past medical history was positive for a sprained ankle. The family history was positive for a maternal grandmother with a herniated disk as an older woman. The review of systems was negative.

The pertinent physical exam showed a healthy female with normal growth parameters and vital signs. Her spine appeared normal. She had generalized stiffness and decreased flexibility in the lumbar spine. No specific flexion, extension, lateral movement or rotational movement of the spine increased the pain or elicited radicular symptoms. She did have a positive straight leg test on both sides but her hamstrings were also tight. She had no specific sensory changes in the lower extremities.

The diagnosis of low back pain that was most likely soft tissue in origin was made. Because it had not improved, and radiologic evaluation using plain radiographs were ordered and were normal. The patient’s clinical course showed she began rehabilitation with physical therapy. Unfortunately after another 2 weeks she continued to have pain and was referred to a sports medicine specialist. Magnetic resonance imaging at that time showed a protrusion of the L4-L5 disk. She was instructed to use high dose oral anti-inflammatory medication, rest and do monitored rehabilitation with the physical therapist. After another 2 weeks with some but not significant improvement she had a steroid injection after which she had pain relief. She continued to do her rehabilitation and slowly over the next 8 weeks she returned to her normal routine.

Discussion
Intervertebral disk herniation occurs at the same locations in pediatric patients as adults with L4-L5 and L5-S1 being the most common. Patients often (30-60% for lumbar disk patients) have a direct trauma or sports related injury that is identified before the onset of pain. There is also a group of morbidly obese patients who probably have degenerative disease. In adults and children, lumbar disk herniation is also seen with repetitive or excessive axial loading, poor conditioning, decreased range of motion and history of prior back injury. Disk herniation is caused by vertebral motion that causes increased intradisk pressure including axial compression, lumbar flexion and/or rotation.

Presentation is usually acute low back pain and/or lower extremity radiculopathy. Pediatric patients often will have less specific descriptions of the pain or complain of other symptoms which leads to longer duration before diagnosis. Disk disease is also uncommon therefore other common causes of back pain are usually sought first. A differential diagnosis of back pain can be found here. “Less than 10% of children presenting with low back pain have disk herniation as the cause, and less than half of those children require surgery.” Causes of back pain that are associated with back extension on physical examination include spondylolysis or spondylolisthesis, and slipped vertebral epiphysis. Problems associated with back flexion on physical examination include disk herniation, apophyseal injuries of the vertebral end plates, Scheuermann disease and Schmorl nodes.

Most patients with a herniated disk will have symptoms with a straight leg raising test and about ~33% will also have a positive crossed straight leg raising test. The straight leg test is considered positive if leg pain (not back pain) radiates below the knee. A reactive scoliosis is also common in pediatric patients with bending toward the contralateral side in an attempt to open up the affected intervertebral space and decrease pressure on the affected nerve. This scoliosis usually resolves with treatment. Patients also often present with generalized stiffness and compensatory gait abnormalities that usually improve with treatment. The bowel and bladder are usually not affected.

Bowel and/or bladder dysinnervation or other progressive neurological deficits, debilitating pain and non-relief with conservative treatment are causes for surgical intervention. Conservative treatment usually includes rest, physical therapy to improve mobilization, flexibility and strength, and anti-inflammatory medication. Pediatric patients with disk herniation f2007 unfortunately respond less well than adults to conservative treatment and are more likely to require operative treatment. This is felt to be because pediatric disks are more elastic and have a higher water content than adults who often have more dried out or degenerative disks. Because of the elasticity operative management also can be more difficult to perform. Open procedures are usually performed and not endoscopic procedures or chemonucleolysis. Surgical treatment has good short term prognosis but 20-30% of patients may require repeated surgical treatment later in life. Plain radiographs of the spine will rule out other causes of back pain such as various fractures and malalignment. Magnetic resonance imaging is the choice for disk disease as it helps to evaluate the soft tissue and neural constituents.

Learning Point
Although intervertebral disk herniation is common in adults, it is relatively uncommon in children. Of patients with disk herniation in various case series, it occurs 0.4%-15.4% in pediatric patient with ~5% being cited often. It is even more infrequent in patients < 10 years of age, but increases in the adolescent population. Gender predominance depends on the study. A positive family history has been reported as a risk factor with presumed weak connective tissue or developing degenerative changes at an earlier age being the proposed explanation.

Questions for Further Discussion
1. What spinal levels correspond to dermatomes in the anterior leg?
2. What spinal levels correspond to dermatomes in the posterior leg?
3. What are indications for referral to a sports medicine specialist?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Herniated Disk and Spine Injuries and Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Slotkin JR, Mislow JM, Day AL, Proctor MR. Pediatric disk disease.
Neurosurg Clin N Am. 2007. Oct;18(4):659-67.

Tsutsumi S, Yasumoto Y, Ito M. Idiopathic intervertebral disk calcification in childhood: a case report and review of literature. Childs Nerv Syst. 2011 Jul;27(7):1045-51.

Lavelle WF, Bianco A, Mason R, Betz RR, Albanese SA. Pediatric disk herniation. J Am Acad Orthop Surg. 2011 Nov;19(11):649-56.

Ho C, Chang S, Fulkerson D, Smith J. Children presenting with calcified disc herniation: a self-limiting process. J Radiol Case Rep. 2012 Oct;6(10):11-9.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Causes Hyperphosphatemia?

Patient Presentation
A 6-month-old male came to the floor of a regional children’s hospital after being transferred from a local emergency room because of abdominal distention. The local emergency room physicans had contacted a local pediatrician who ordered an enema for the patient. The patient received the enema but had no fecal return. He continued to have abdominal distention and the decision to transfer him was made. Upon arrival at the children’s hospital the patient had bradycardia and a respiratory arrest. After intubation his heart rate increased to normal and he had spontaneous respirations. In the pediatric intensive care unit the pertinent physical exam showed a temperature of 99.8°F, heart rate of 128, respiratory rate of 22, blood pressure of 104/62 with a capillary refill of 3-4 seconds and pale color. He had a grossly distended abdomen without bowel sounds. He had a normal heart rate and sounds. His lungs were clear. He also had intermittent extremity spasms especially of his hands and feet. The pertinent laboratory evaluation at that time showed a glucose of 23 mg/dl, ionized calcium of 1.3 (normal 4.5-5.6 mg/dl), total calcium of 7.4 (normal 9.0-10.5 mg/dl), phosphorous of 28 (normal 3-4.5 mg/dl) and magnesium of 1.9 (normal 1.8-3.0 mg/dl). The differential diagnosis at that time included sepsis with ileus, volvulus, appendicitis with perforation (unlikely due to age), pseudoobstruction, bowel perforation, and metabolic abnormalities. The past medical history that became available later revealed a term infant who stooled around birth but had problems with constipation. A previous rectal biopsy had shown ganglion cells and his neonatal screening test was normal including for cystic fibrosis. He had been treated with oral polyethylene glycol and occasional enemas for constipation. The family history was negative for genetic, metabolic, neurologic or gastrointestinal problems. He was treated for presumed sepsis and hypocalcemia, hypoglycemia, and hyperphosphatemia with aggressive hydration, calcium gluconate, ampicillin, gentamycin and metronidazole, and rectal irrigation.

His clinical course over the next 24 hours, showed having tetany episodes that improved with additional calcium, but eventually his hypocalcemia, hypoglycemia and hyperphoshatemia all resolved. His blood cultures later grew Enterococcus species as a cause of his sepsis. He unfortunately had an ileal perforation that required an ileostomy. During surgery there was normal bowel anatomic alignment and biopsy of various bowel segments showed ganglion cells in all biopsies. Cystic fibrosis and other testing for severe ileus with perforation was being pursued. The tetany and metabolic problems were felt to be caused by the retention of a phosphate-based enema with resulting hyperphosphatemia and hypocalcemia which caused cardiac irritability and cardiopulmonary arrest.

Case Image
Figure 120 – Supine view of the abdomen reveals multiple dilated loops of bowel without evidence of rectal gas. The findings were felt to be compatible with a distal bowel obstruction.

Discussion
Constipation is a common problem in general pediatrics and its causes are numerous. It can cause acute and recurrent abdominal pain and is a cause of abdominal distention. Patients who are young, whose presentations are other than routine or who had complications should be invested for underlying causes of their constipation. This patient had undergone some evaluations in the past for constipation but because of the presentation of sepsis a more rigorous evaluation was undertaken. The differential diagnoses of the following can be found here: constipation, acute abdominal pain, recurrent abdominal pain, and abdominal distention.

Hyperphosphatemia caused by retention of oral phosphate containing medications and hypertonic sodium phosphate enemas are known causes of hyperphosphatemia. Phosphate-containing medications are used because the hyperosmolarity draws fluid into the intestinal lumen which stimulates peristalsis. Usually the phosphate and fluid are then evacuated. However, the phosphate can be absorbed, particularly if there is lack of bowel integrity, with resulting hyperphosphatemia. With rising concentrations of phosphate, calcium is bound causing hypocalcemia both extracellualrly and intracellularly. Hyperphosphatemia also inhibits Vitamin D hydroxylation and inhibits reabsorption of calcium in the bone. While hypocalcemia is the most common secondary problem due to hyperphosphatemia, hypokalemia, hypomagnesemia and hypoglycemia can also occur. Phosphate toxicity is treated by increasing urinary excretion, phosphate binders (such as aluminum hydroxide) and dialysis.

Hypocalcemia is associated with neuromuscular problems including irritability, poor feeding, emesis, paresthesia, muscle cramps (tetany) seizures, prolongation of the QT interval and cardiac arrhythmias. Chvostek’s sign occurs when tapping on the facial nerve causes facial muscle movement. It is common in hypocalcemia but can also be seen in hypomagnesemia, normal individuals, and patients with migraines or epilepsy. Trousseau’s sign occurs when a blood pressure cuff is inflated around the arm at a pressure greater than systolic pressure for 3 minutes and induces a spasm of the hand and forearm. This also occurs with hypocalcemia. Acidosis and hypoproteinemia tend to protect patients from secondary hypocalcemia problems by increasing the ionized fraction of serum calcium. Hypocalcemia is treated by giving calcium by judicious infusions with either calcium gluconate or calcium chloride. A differential diagnosis of hypercalcemia can be reviewed here.

Learning Point

Phosphate is mainly regulated by parathyroid hormone and dietary/gastrointestinal intake. Therefore hyperphosphatemia occurs primarily because of disregulation to these systems.
The differential diagnosis of hyperphosphatemia includes:

  • Phosphate containing medications and bisphosphonates
  • Renal failure – acute or chronic
  • Hypoparathyroidism
  • Vitamin D toxicity
  • Tumor lysis syndrome
  • Tissue necrosis
  • Rhabdomyolysis
  • Hyperostosis
  • Familial tumoral calcinosis
  • Pseudohyperphosphatemia
  • Acromegaly

Questions for Further Discussion
1. What causes changes in magnesium?
2. What causes changes in potassium?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Fluid and Electrolyte Balance and Minerals.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Oxnard SC, O’Bell J, Grupe WE. Severe tetany in an azotemic child related to a sodium phosphate enema. Pediatrics. 1974 Jan;53(1):105-6.

Hebbar K, Fortenberry JD, Parks JS. Severe hypocalcemic tetany and respiratory failure in an infant given oral phosphate soda. Pediatr Emerg Care. 2006 Feb;22(2):118-20.

Domico MB1, Huynh V, Anand SK, Mink R. Severe hyperphosphatemia and hypocalcemic tetany after oral laxative administration in a 3-month-old infant. Pediatrics. 2006 Nov;118(5):e1580-3. Epub 2006 Sep 25.

Stubbs JR, Yu ASL. Overview of the causes and treatment of hypophatemia. UpToDate. (rev. 7/6/2015, cited 6/27/16).

Hasan ZU, Absamara R, Ahmed M. Chvostek’s Sign in Paediatric Practice. Current Pediatric Reviews, 2014:10;194-97.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital