Liver Transplants Increase Survival Rate for Non-Resectable Colorectal Liver Metastases

Cancer of the colon (also known as colorectal cancer) is uncontrolled abnormal cell growth in the colon or rectum (parts of the large intestine). Because the liver is situated above the large intestine, it is not uncommon for cancer to spread (metastasize) from the latter to the former. When this happens, it is known as a colorectal liver metastasis or CLM.

Many patients with CLMs have non-resectable disease, meaning that the cancer cannot be surgically removed without replacing the entire organ. However, because these cancers tends to re-occur, because the long-term survival rates are poor (few survive more than 5 years), and because so few donor livers are available in most countries, as of 1995 a decision was made in the medical community that liver transplants were no longer to be performed for patients with CLMs. The only option this leaves such patients is chemotherapy which has a very poor prognosis (5 year survival rate of less than 10%).

Researchers in Oslo, Norway, are challenging this way of thinking, especially since liver transplants offer the chance for a cure and because survival after liver transplants has improved by as much as 30% over the past two decades. The researchers decided to perform an initial study and use liver transplants as a treatment for 21 patients with non-resectable CLMs. The study was done relatively easily in Norway because in that country there is actually a liver donor surplus, where the wait for a liver donor is less than a month (in the U.S. it can take years to find a liver donor and many people die before one is available).

In the study, 21 patients with CLMs received liver transplants. None of the patients had detectable cancer that spread to other parts of their body, the main (primary) tumor in the colorectal area had been removed already, and the patients received at least  six weeks of chemotherapy. The study results were a great success, showing that 95% of patients had survived after one year, 68% survived after 3 years, and 60% survived after 5 years.  Compare this to prior to 1995 when only 62% of patients survived liver transplants after CLMs one year later and only 18% survived 3 years later. Additional good news reported in the study was that for patients who had a cancer recurrence after liver transplant, a significant proportion of these were accessible for surgical removal and after a median follow-up of 27 months, 33% had no evidence of disease. The results of the Norway study are soon to be published in the Annals of Surgery.

Suggested reading:  American Cancer Society's Complete Guide to Colorectal Cancer

Related blog entry: Colonoscopy Prep Made Easy: A New Cleanser

Reference:  Hagness M, Foss A, Line PD, Scholz T, Jørgensen PF, Fosby B, Boberg KM, Mathisen O, Gladhaug IP, Egge TS, Solberg S, Hausken J, Dueland S. (2013, in press). Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer. Ann Surg.

The Dangers of Home Canning: A Case of Botulism

In the current issue of The Annals of Pharmacotherapy, a case is reported of a 60-year-old man who presents to an urgent care center with blurry vision, double vision, and difficulty speaking. The doctor is concerned that he may be having signs and symptoms of a stroke and sends him to the Emergency Room (ER) for evaluation.

A stroke is a burst artery (a type of blood vessel that carries blood away from the heart) or a blockage of an artery in the brain.

In the ER, the physical examination and diagnostic imaging of the brain showed no evidence of stroke. So the doctor orders standard blood tests but they do not yield anything of significance. The doctor wants to do some more studies and admits the patient to the hospital. A more sensitive imaging study of the brain was ordered the next day but the patient could not lie down due to a choking feeling. He was transferred to the intensive care unit (ICU) that day due to difficulty swallowing, difficulty speaking, nausea, dizziness, mild tremors in the arms and legs, and eyelid drooping. A test of heart functioning was normal. The next day, due to worsening breathing, he had a tube placed down his throat and was placed on a ventilator. He could not open his eyes without assistance.

In gathering the history, it was revealed that the man consumed home-canned corn several hours before admission. He had received it in a gift basket. The can was tested and revealed the course of the problem: foodborn botulism. A specialized blood test revealed this as well. 

Botulism is a rare and sometimes deadly illness cause by botulinum toxin, a poisonous protein caused by the bacteria, Clostridium botulinum. This powerful toxin leads to paralysis (loss of movement and/or sensation) that usually starts in the face and progresses to the arms and legs. Mr. X eventually developed  generalized weakness along with his breathing problems. When botulism comes from food, it is typically from home canning of low acidic foods. This is because Clostridium botulinum is anaerobic, which means it does not require oxygen for growth, and because it thrives in low acidic environments. Since it is common on food surfaces, it can thrive when placed inside of a can (where there is no oxygen or very little oxygen), particularly in low acidic foods such as corn, green beans, and beats.

The modern canning industry uses procedures to control the risk of botulism (e.g., pressure cooking at 121 degrees Celsius for 3 minutes, following strict hygiene) but many people who use home canning do not because they are unaware of the risks and what to do to prevent it. When consumed, signs and symptoms usually begin within 12 to 72 hours. About 24 cases of foodborn botulism occur in the U.S. per year.

So how did the story end for the 60-year-old man? Many more details are provided in the case study, but he was treated with an anti-toxin known as heptavalent botulism antitoxin (H-BAT) but his and he discharged to a long-term acute care facility after 22 days in the hospital. Because the diagnosis was not immediately determined and treatment was delayed for days, he did not receive many of the same treatment benefits that would be expected if the condition was realized sooner.

Suggested reading: Canning for a New Generation: Bold, Fresh Flavors for the Modern Pantry

Reference: Hill SE, Iqbal R, Cadiz CL, Le J. (2013). Foodborne botulism treated with heptavalent botulism antitoxin. Ann Pharmacother. 47(2) :e12.

The Health Impacts of a Surprise Russian Meteor Strike

On the morning of 2/15/13, in Chelyabinsk, Russia, residents were shocked to see and hear a mixture of fire and smoke streaking in the sky at 40,000 mph.

Although they did not know it at the time, the source of the smoke and fire was a 10-ton meteor that was 55-feet in diameter. The meteor exploded in the sky 18 to 32 miles above ground. This set off a shock wave blast that was reportedly the strength of 10 to 30 Hiroshima atomic bombs. It was the largest meteor to hit the Earth since 1908 (which interestingly also happened in Russia). The blast reportedly injured 1158 people (including 298 children), leaving 52 hospitalized (37 of whom were released by the next day), but fortunately, no one was killed. However, if the meteor had landed at ground level, it reportedly would have probably destroyed every single building in an area as wide as Chicago and there would have certainly been a high fatality rate.

There are various ways that a shock wave blast can cause injury. First is what is known as the primary pressure wave injury, which is injury caused by the changes in the atmosphere caused by the explosion. The organs that are most vulnerable to this type of injury are those with air-fluid interfaces, such as the lungs, intestines, or inner ear. These tend to be hollow body parts. The most common type of injury from a primary pressure wave explosion is an eardrum rupture.  This is why footage from people reacting to the blast shows people instantly covering their ears and reporting temporary deafness.

Then there are secondary blast injuries, in which the force of the explosion causes objects in the area to fly through the air, strike someone, and cause bodily injury. For example, this can cause a brain injury, since an object (e.g., glass, rocks, household item, wooden plank, etc.) can fly through the air at considerable force and cause blunt trauma to the skull and its underlying contents. Obviously, other parts of the body (e.g., arms, legs, internal organs) can be injured as well, as manifested by muscle tears, bone breaks, and internal bleeding. For example, one person’s finger was cut off by broken glass. One teacher was reported to have saved 44 children from glass injuries by ordering them to hide under their desks when she saw the flash. Unfortunately, the teacher suffered a serious laceration of an arm tendon. Tendons are groups of fibers that attach muscles to a bone.

A tertiary injury is when the force of the explosion causes the person to be thrown into solid object such as a wall. Clearly, this can also cause significant injury if the person is thrown forwards or backwards with enough force. It can also cause injury by being thrown down a flight of stairs, which happened to one woman, causing her to break two vertebrae (bones in the neck that make up part of the structure surrounding the spinal cord).

Lastly, quaternary blast injuries are injuries caused by the aftermath of the blast. These types of injuries usually include burns, chemical and toxic dust inhalation poisoning, radiation exposure, and crush injuries due to building collapse.  There are many pictures of broken parts (wall and roof) of zinc building from the meteor blast, which is known to have hurt people.

Another health risks related to the meteor damage has to do with the event occurring over the winter due to the subzero temperatures that often occur this time of year in that part of Russia. This places people at risk of hypothermia (abnormally decreased body temperature) because of the windows that were blown out. Thus, repairing and replacing open living structures is of high priority as is finding people who are particularly vulnerable (e.g., elderly, young children, the poor) and keeping them warm with blankets, extra clothing, etc.

Hopefully, scientists will be able to develop better ways to detect meteors coming to earth and find ways to prevent them from causing significant damage and harm. In the U.S., NASA has been charged by Congress to constantly monitor the skies for incoming objects. Rather than trying to shoot down such objects, some scientists advocate for impacting the asteroids to slow them down or speed them up so they do not enter the Earth’s atmosphere. But you probably should not lose too much sleep over it. Scientists say this was a 1 in 100 year incident.

Suggested reading: Field Guide to Meteors and Meteorites

Geriatric Syndromes: The Role of Vascular Disorders

A geriatric syndrome is a general term used to refer to clinical conditions with multiple possible factors that are common among the elderly and associated with increased disability, nursing home placement, and death. Examples include impaired thinking, heart disease, dizziness, and impaired hearing and vision, among many others.

In an upcoming article in the Annals of Medicine, researchers from Finland argue based on a synthesis of prior research that vascular factors are an important cause of geriatric syndromes. Such vascular factors include aging and dysfunction of large and small blood vessels, cardiovascular diseases, and hardening of the arteries. An artery is a blood vessel that carries blood away from the heart. As the researchers note, small vessel disease can lead to blockages, which decreases blood supply to organs such as the brain, heart, kidney, retina, muscles, and bone. In fact, they argue that small vessel disease can affect any cell in the body because all cells are ultimately dependent on a proper blood supply to deliver oxygen.

In the article, the researchers provide evidence that even vascular disease that does not cause signs or symptoms is associated with frailty. They note that muscle loss can be caused by decreased blood supply of oxygen. They note that dementia is known to be caused by cerebrovascular disease but that other forms of dementia such as Alzheimer’s disease (considered to be separate) often co-occurs with cerebrovascular disease and that vascular pathology (e.g., hardening of the arteries) may contribute to its development. Dementia is a progressive loss of cognitive and intellectual functioning without loss of consciousness.

The researchers discussed some evidence that vascular factors increased the risk of delirium. Delirium is a state of fluctuating mental confusion that develops over a few hours or days. The authors are careful to note that while vascular factors can contribute to depression, neglect, and apathy (lack of interest) that these three problems can worsen vascular disorders. Thus, the relationship runs in both directions.

The researchers noted that subtle connections were emerging on the role of vascular disorders and urinary incontinence (loss of urinary control). An example is decreased oxygen to the frontal lobes, which works as the brain’s executive control center. If something goes significantly wrong it that part of the brain, the person will likely have difficulty with impulse regulation. The article discusses how disturbances of gait (walking) can by caused by vascular damage to the white matter of the brain, which can cause falls and bone breaks.

White matter is a group of white nerve fibers that conduct nerve impulses quickly. Vascular links to dizziness, hearing impairments, visual impairments, and osteoporosis is also presented. Osteoporosis is an abnormal loss of bone thickness and a wearing away of bone tissue. Earlier detection and treatment of vascular disease can hopefully lead to a decrease in geriatric syndromes over time.

Suggested reading: TOP 10 Geriatric Syndromes Clinical Management Strategies

Reference: Strandberg TE, Pitkälä KH, Tilvis RS, O'Neill D, Erkinjuntti TJ. (2013, in press). Geriatric syndromes-vascular disorders? Ann Med.

Patient Centered Medical Homes: Do They Work?

In a prior blog entry, it was noted that over-use of the Emergency Room may be facilitated by the implementation of “patient centered medical homes” (PCMH). A PCMH is a team-centered health care system led by a medical doctor, nurse practitioner, or physician assistant to provide comprehensive and continuous health care.

In the PCMH model, two or more clinicians work together to coordinate health care. The PCMH model is designed to do two or more of the following: a) provided enhanced access to care (e.g., 24-hour coverage), b) coordinated care, c) comprehensive care (i.e., can take care of most of a person’s medical needs), and d) uses a systems-based approach to improve quality and safety. The PCMH model is designed to develop a sustained relationship with the patient and reorganizes traditional health care delivery practices.

At present, there are not many medical homes in the U.S., but the numbers will expand greatly as part of health care reform. While PCMHs are often said to have great promise, is there evidence that they actually work to improve most clinical outcomes (e.g., improved management of health conditions) and economic outcomes (e.g., decreased healthcare costs)?

In a recent article in the Annals of Internal Medicine, researchers examined 19 comparative studies to determine the effectiveness of PCMH interventions.  The results were less than stellar. Specifically, there was no evidence that the PCMH model reduced overall medical costs. There was a small positive effect on patient experiences and a small to moderate effect on the delivery of preventive care experiences.  Staff experiences were improved by a mild to moderate degree. While the study showed that there was a reduction in ER visits, consistent with what was suggested earlier, admissions to the hospital were not decreased for older adults. The authors concluded that the PCMH model holds promise but that the current evidence is insufficient regarding its effective on clinical outcomes and most health outcomes. 

Suggested reading: ObamaCare Survival Guide
 
Reference: Jackson, G., et al. (2013). The Patient Centered Medical Home: A Systematic Review. Annals of Internal Medicine. 158, 169-178.

Abdominal Obesity in Brazilian Adolescents

There has been much talk in the media about the obesity epidemic in children in the United States and in other countries. Obesity is a problem because it leads to increased risk of other health problems such as heart disease and diabetes mellitus.

Diabetes mellitus is a complex, long-term disorder in which the body is not able to effectively use a natural chemical called insulin. Insulin's main job is to quickly absorb glucose (a type of sugar) from the blood into cells for their energy needs and into the fat and liver cells for storage.

In the most recent issue of the Annals of Human Biology. researchers examined the prevalence of abdominal obesity in Maringa, Brazil and the behaviors associated with this. The study evaluated 991 adolescents (54.5% girls). Abdominal obesity was defined by the waist circumference. Of the adolescents studied, the abdominal obesity prevalence was 32.7% (girls = 36.3% and boys = 28.4%). The researchers stated that the higher percentage in girls may because females tend to have a higher percentage of body fat than males.

In both genders, abdominal obesity was associated with having a job. It is unclear exactly why this was the case, however. Girls with abdominal obesity had high levels of soda consumption. This is because soda is known for a high level of simple carbohydrates that raises glucose levels but does not always provide a feeling of fullness. Interestingly, obese females were less like to consume excessive levels of fried foods. Among males, the obese were less likely to consume excessive amounts of sweets and soda. The authors noted that this could have been related to dieting behaviors, however. In other words, they may have been reducing consumption of sweets and soda because in reaction to being obese.

Suggested reading: Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease

Reference: de Moraes AC, Falcão MC. Lifestyle factors and socioeconomic variables associated with abdominal obesity in Brazilian adolescents. Ann Hum Biol. (2013) 40(1):1-8.

Genetic Screening Test for Familial High Cholesterol

Cholesterol is a waxy, fatty substance found only in animal tissues. Good cholesterol helps to eliminate bad cholesterol. There are two types of cholesterol: good cholesterol (also known as HDL which stands for high-density lipoprotein) and bad cholesterol (also known as LDL which stands for low-density lipoprotein).

LDL is called bad cholesterol because it can cause cholesterol to build up, which can lead to blockage of the arteries and heart disease. Arteries are blood vessels that pump blood away from the heart.

Cholesterol levels are easily detected through a routine blood test known as a lipid panel. When the doctor believes cholesterol is too high, lifestyle changes (e.g., increased exercise, diet changes) and medications may be prescribed.

While high cholesterol can be caused by a poor diet and not enough exercise, genetics can also play a role. In other words, some people have what is known as familial hypercholesterolemia, which is a fancy way of saying that the person has inherited very high levels of bad cholesterol from one or both parents, which leads to heart disease.

Unless someone goes for testing, the condition may not be detected because it usually does not cause symptoms. However, it can cause the sign of yellowish patches on the body due to cholesterol deposits. The condition is caused by mutations of genes. Genes are tiny structures that contain coded instructions for how certain bodily characteristics should develop.

To diagnose the condition early, some scientists have suggested using genetic screening methods. However, some have expressed concern that this can lead to an unacceptably high level of false positives, in which people are told they have the condition when they do not. One type of genetic testing is analyzes for genetic mutations that cause high cholesterol and is known as the High-Resolution Melting (HRM) method.

In the most recent issue of the Annals of Human Genetics, the HLRM method was used on eight unrelated people (7 females and 1 male) from Croatia known to have familial hypercholesterolemia. The test was positive in 7 cases (88%) in which the mutation causing the problem was found. The researchers concluded that the HLRM method is sensitive for detecting familial hypercholesterolemia, which can lead to earlier treatment and detection in other family members, which in turn, can prevent premature heart disease. One problem with the study is however is that no controls (people without the condition) were tested so the false positive rate is unknown. The study also has limited generalizability as it was mostly done with Croatian women.

Suggested reading: Cholesterol Down: Ten Simple Steps to Lower Your Cholesterol in Four Weeks--Without Prescription Drugs
  
Reference: Pećin I, Whittall R, Futema M, Sertić J, Reiner Z, Leigh SE, Humphries SE. (2013). Mutation detection in Croatian patients with familial hypercholesterolemia. Ann Hum Genet. 77(1):22-30.

How Long Should a Cough Last?

An acute (sudden) cough illness (ACI) is one of the main reasons people seek outpatient medical care from a family physician or pediatrician. Many of these cases are caused by acute bronchitis or bronchiolitis. Bronchitis is inflammation of the bronchial tubes, which are airways that connect that windpipe to the lungs.

Bronchiolitis is inflammation of the bronchioles, which are small airways that branch off the other small airways connected to the lungs.

The cause of ACI is usually a virus but patients often seek antibiotic treatment for it. The problem, though, is that while antibiotics are good at treating bacterial infections, they do not work at treating viruses. When antibiotics are prescribed for viral illnesses, it is referred to as antibiotic overuse. Overuse of antibiotics increases the risk that antibiotic-resistant bacteria will develop.

Many doctors are prone to prescribing medications in response to patient pressure (or pressure from the family). These pressures result from patient expectations on how long an acute cough should last without treatment.

In the most recent issue of the Annals of Family Medicine, researchers examined how closely patient expectations of acute cough duration matched reality. After a comprehensive literature search, the researchers found 19 studies across the world that helped them determine the average length of an untreated acute cough in otherwise healthy adults. They found that the average length of any cough was about 18 days. The average length of a cough that produced something to spit out (i.e., productive cough) was 13.9 days. 

The researchers then surveyed 493 adults in Georgia to determine their expectation on the average duration of an acute-onset cough. Depending on the specific scenario, patients expected an average cough duration of about 7 to 9 days. As the researchers explained, if the expectation of acute cough duration is wrong, it can lead to false conclusions by the patient in terms of the effectiveness of the antibiotic. For example, if a patient with an acute viral cough expects that it should only last for 7 days, seeks antibiotic treatment, and receives it, the patient will likely falsely conclude that the antibiotic cured the cough when it would have resolved anyway in 18 days. The researchers provided evidence supporting that such beliefs exist.

The researchers concluded that a better understanding of the typical duration of acute cough could reduce patient demands for antibiotics. They suggested that doctors help educate their patients about the normal length of acute cough and that they should only seek care if the cough worsens or if other alarming signs and symptoms develop such as fever, shortness of breath, or coughing up blood.

Suggested reading: Breaking the Antibiotic Habit: A Parent's Guide to Coughs, Colds, Ear Infections, and Sore Throats

Reference: Ebell, M., Lundgren, J., Youngpairoj, S. (2013). How Long Does a Cough Last? Comparing Patient’s Expectations with Data from a Systematic Review of the Literature. Annals of Family Medicine, 11, 1, 5-13.

Medicaid/CHIP: The Emergency Room Gateway to Specialists

Medicaid and CHIP (Children's Health Insurance Program) are two types of public insurance for adults and children, respectively. While these insurances provide an important safety net for people, they are notorious among health care providers for extremely low levels of reimbursement compared to other types of insurance (e.g., private, no-fault, workers compensation).

These insurances are also widely known for denying coverage for overly technical reasons (e.g., not adding a decimal point in a billing code) and for bogging health care providers down in paperwork. Accepting such patients also carries the risk of a government audit, which can have serious consequences (e.g., large fine and/or jail time) if found guilty of violating the rules.  Patients with Medicaid and CHIP also tend to have high no-show rates.

As such, many private outpatient health care providers refuse to see patients with these types of insurances. Even in public health care settings (e.g., state hospitals) where it is not legal to deny evaluations patients with these insurances due to government contracts, the numbers of patients seen per day, per week, or per month with these insurance are often capped.  These problems are becoming more and more salient across the country due to increasing economic strain caused by various factors such as declining reimbursement in general, decreased government financial aide, and the impacts of health care reform. As a result, many health care providers are under increasing pressure from the institutions they work in to bring in more money. This often means seeing more patients with higher paying insurances.

All of this creates a serious problem for patients who have Medicaid or CHIP who need to be seen by outpatient specialists (e.g., neurologists, psychologists, psychiatrists, gynecologists).  It is also a problem for the primary care physicians (PCPs) who refer these patients because without input from the specialist it is much more difficult to coordinate care.

If the patients calls the specialist office themselves, one of the first questions they will be asked is “What insurance Do You Have?” If the answer is a private insurance, the patient will often be seen relatively quickly. If it is Medicaid or CHIP, there is a much greater chance of being put on a waiting list, given an appointment many months later, or told there are no appointments at this time.  The same can hold true if a staff member from a PCPs office calls the specialist’s office to make the appointment.

Due to this problem, patients with Medicaid and CHIP and their PCPs find ways to work around these obstacles. One of the most effective ways this is done is by going to the Emergency Room (ER), even though the medical situation may not be a true emergency. In an upcoming article in the Annals of Emergency Medicine, researchers explored this topic more by interviewing 26 specialists and 14 primary care physicians in Illinois.

The results of the study confirmed much of what was discussed above, including how the ER is used by PCPs and patients to access specialty care. The study also found that specialists will often take patients from the ER out of sense of obligation and because referrals from the ER often have established mechanisms in place to distribute these patients equitably so that no one provider is seeing too many low-paying patients. Referrals from PCPs, however, often do not have such equitable distribution mechanisms. Specialists are also more likely to take patients from the ER is the specialty service is affiliated with the ER in some way (e.g., located in the same hospital). For urgent situations that a patient cannot get an outpatient specialist to evaluate for many months, showing up in the ER usually means that the specialist will be paged to see him/her that day for an evaluation.

Other factors that the study found was associated with the specialist accepting a Medicaid/CHIP patient was a personal request (i.e., call) from the PCP, informal economic relationships between the specialist and PCP, patient hardship, the more urgent the case was, and geography. With regards to the latter, it appeared that providers were more willing to see Medicaid/CHIP patients who lived closer to their office (probably because it decreased the no-show risk that can result from transportation problems).

Suggested reading: Confessions of Emergency Room Doctors

Related Blog Entry: Who Uses the Emergency Room Most? The Answers May Surprise You

Reference: Rhodes KV, Bisgaier J, Lawson CC, Soglin D, Krug S, Van Haitsma M. (2013, in press). "Patients Who Can't Get an Appointment Go to the ER": Access to Specialty Care for Publicly Insured Children. Ann Emerg Med.

Child Paralyzed after Tonsils Removed

In an upcoming article in the journal, Anaesthesia, a case study was reported in which a 7-year old boy in India developed quadriplegia after an elective surgery to remove his tonsils and adenoids. Quadriplegia is a loss of the ability to move and/or feel both arms, both legs, and the parts of the body below the area of injury to the spinal cord. The tonsils are a pair of oval masses at the back of the throat.

The adenoid is a mass of tissue behind the nasal cavity, where the nose blends into the throat. The tonsils and adenoid are often surgically removed in children if they become large enough to obstruct airflow.

During the surgery of the 7-year-old child, he was treated with two types of powerful anesthesia known as fentanyl and thiopental. This was maintained with two forms of inhaled anesthesia known as isoflurane and nitrous oxide. The muscles were relaxed with another medication (atracurium). The surgery lasted 40-minutes. After surgery, he was drowsy and not breathing spontaneously. Medication was administered to try and reverse the muscle relaxing effects of anesthesia, but the breathing problems continued, and she became agitated and weak in all four limbs.

Although residual effects of anesthesia are sometimes the cause of these problems, the authors of the case report noted that a more serious cause should be explored the longer they persist. Initially, no obvious cause could be found. To investigate the situation further, the boy was sent for an x-ray and MRI (magnetic resonance imaging) of the spine. MRI scans produce extremely detailed pictures of the inside of the body by using very powerful magnets and computer technology. The results revealed a previously undetected condition known as atlanto-axial instability (AAI), which is increased flexibility between the first and second bones of the neck. He underwent surgery to fixate these bones and had  a slow but complete recovery of motor power over 7-months. He still needs some slight supplemental oxygen support.

As it turns out, the child has been evaluated before surgery for what were signs and symptoms of AAI, but the doctor falsely attributed them to failure to thrive due to tonsil disease despite a neurological exam showing weakness in the arms and legs, muscle wasting, and abnormal reflexes. The signs and symptoms included tiredness, poor weight and height gain, difficulty climbing stairs, and mild neck pain,

Because AAI was not recognized, when the head and neck were moved around during the surgery, the authors stated that the head hyperextended which resulted in a subluxation (signification structural displacement ). This, in turn, caused compression of the cervical spine. This compression causes impairment of the nerve signals that normally travel through this area of the spinal cord. It resulted in quadriplegia in this case because the compression was in the cervical (neck) region below which impulses regarding sensation and movement travel to and from the arms and legs.

The authors noted that the most common warning sign of AAI (85% of cases) is neck pain and headaches in the back of the head that radiate to towards the top of the head.  However, because signs and symptoms of AAI may be misinterpreted and because some patients may have no signs and symptoms, the only definitive way to detect it is with diagnostic imaging. Although the authors did not suggest performing x-rays or other imagine scans on patients before surgical procedures, it would be the only way to know for sure. However, exposure to radiation from x-rays and high financial causes of more advanced scans are likely barriers to this happening.  

Suggested reading: Walk, Don't Run: One Woman's Battle with Quadriplegia, A Memoir of Hope and Healing
 
Reference: Agarwal J, Tandon MS, Singh D, Ganjoo P. (2013, in press). Quadriplegia in a child following adenotonsillectomy. Anaesthesia.

Ovarian Tumors in Children: They Happen

When people think of ovarian tumors, they most commonly think of women. However, ovarian tumors (also known as neoplasms) can also occur in children. Tumors are abnormal masses of tissue that form when cells in a certain area of the body reproduce at an increased rate.

The ovaries are a pair of glands that contain the eggs (female reproductive cells) and produce female hormones. Hormones are natural chemicals produced by the body and released into the blood that have a specific effect on tissues in the body.

Most ovarian tumors in children are known as germ cell tumors. As the name implies, these are tumors derived from germ cells. Germ cells are any cells that give rise to other cells that fuse with another cell during fertilization. These types of tumors can be cancerous (malignant) or non-cancerous (benign). Cancer is any of a large group of malignant diseases characterized by an abnormal, uncontrolled growth of new cells in one of the body organs or tissues.

The second most common type of ovarian tumor in children is the surface epithelial neoplasm, although information about them in children is limited. These tumors can also be cancerous or non-cancerous and arise from the epithelial surface of the ovaries, endometrial tissue (lining of the uterus) that is out of place, of Fallopian tube tissue. The uterus is a hollow organ in a female's body where the egg is implanted and the baby develops. Fallopian tubes are two structures that serve as passageways from the ovary to the uterus.

In an upcoming issue of the American Journal of Surgical Pathology, researchers reported detailed findings on surface epithelial neoplasms in children at the Stanford University School of Medicine between 1974 to 2010. Over that 36 year time frame, the researchers found 69 such tumors in 64 children. In 57.8% of the cases, the tumors were non-cancerous. In 37.5% of cases, the tumors were of borderline/low malignant potential. Only 4.7% of these tumors were malignant but no high-grade tumors (fast growing and aggressive) were found. This is unlike adults, where a high percent of high-grade ovarian tumors are found.

The types of surface epithelial neoplasms in children were classified as serous, mucinous, or mixed (different subtypes combined). The serous tumors are filled with serous fluid, a type of pale yellow and transparent body fluid. The mucinous tumors are made of epithelial cells in which the apical surface is lined with mucin (a gel-like secretion). The apical surface is the part of the cell exposed to the lumen (the inside space). 

Of the 64 children, 17 had follow-up data obtained on average 22 years later. Of these patients, recurrences occurred in about 12% of benign tumors, 33% of borderline/low malignant potential tumors, and 100% of malignant tumors. Recurrences occurred anywhere between 11 to 144 months after initial diagnosis and mostly occurred in the same ovary suggesting that incomplete surgical removal of the tumor was the likely cause of recurrence. Recurrence rates were similar in the 3 subroups (serous, mucinous, mixed). While all children with benign and borderline/low malignant ovarian tumors survived, only half of children with malignant ovarian tumors survived.

The authors noted that although two patients were treated with chemotherapy and one with sterilization procedures, that most cases can be treated by surgically removing the tumor. The researchers advocated for uniform treatment models, conserving the ovary, and trying to preserve fertility in any child with a suspected ovarian surface epithelial lesion.

Suggested reading: Memoir of a Debulked Woman: Enduring Ovarian Cancer

Related blog entries: Ovarian Cancer: Treatment with Avastin

Childhood Tumors: How PET/CT Scans Can Help
 
Reference: Hazard FK, Longacre TA. (2013, in press). Ovarian Surface Epithelial Neoplasms in the Pediatric Population: Incidence, Histologic Subtype, and Natural History. Am J Surg Pathol..

Rocky Mountain Spotted Fever: Knowledge Gaps in Health Care Providers

Rocky Mountain spotted fever (RMSF) is the most deadly and most common illness caused by Rickettsia, a group of bacterial parasites. A parasite is an organism that lives in or on another organism to obtain nourishment. The specific type of Rickettsia that causes RMSF is known as Rickettsia rickettsi, which is spread by a group of ticks known as Dermacentor ticks (American dog ticks).

Signs and symptoms of Rocky Mountain spotted fever include an acute (sudden) onset of fever, muscle pain, and headache one to two weeks after a tick bite. This makes RMSF initially appear flu-like, which can delay accurate diagnosis and treatment. This is followed by a rash in about 80-90% of cases. The initial rash begins about 2 to 5 days after fever onset and is initially small, pink, flat, and not itchy. The rash begins on the arms and legs and moves towards the trunk. The spotted rash for which the disease is named after is red but only develops in 35 to 60% of cases. The disease can affect the brain, kidneys, intestines, and lungs.

RMSF can cause severe long-term health problems, which is why knowledge of proper treatment is essential. Delays in treatment can cause severe problems including paralysis, loss of hearing, amputation, loss of bladder control, loss of bowel control, disorders of speech and movement, and death. Standard of care treatment for adults and children of all ages is antibiotics, specifically doxycycline. Doctors recommended beginning this treatment even before laboratory confirmation of the disease. The treatment continues for at least three days after the fever stops and until there is clear improvement of the patient. Treatment usually lasts for a total of 5 to 10 days, but can last longer in more severe cases.

RMSF gets part of its name from the Rocky Mountain Laboratories, which is where much of the early research in this condition began. The disease can and does present throughout most of the U.S. and some other countries. Thus, it is not isolated to the Rocky Mountain region. One state outside of the Rocky Mountain region where RMSF is very common is Tennessee. This is because the tick that causes the disease is common in the southeastern U.S.

In the most recent issue of the American Journal of Tropical Medicine and Hygiene, researchers presented the results of a survey of 1,139 Tennessee healthcare workers (physicians, nurse practitioners, physician assistants) on their knowledge, perceptions, and attitudes on RMSF diagnosis and treatment. About 90% of those surveyed were current practicing and most surveyed were physicians. The response rate in the study was low (14%) which limits the generalizability of the results.

While 93% of respondents correctly identified that doxycycline was a treatment they would use in RMSF, only 39% correctly identified that doxycycline was the treatment of choice for RMSF in children younger than age 8. This was particularly a problem among family medicine and emergency room physicians, which can lead to unnecessary deaths among children. Twenty percent of providers preferred to wait for a rash to develop to initiate treatment, which is a problem because by the time a rash develops (if it develops) it may be too late to begin effective treatment.

Only 42% of providers correctly identified the fatality rate of untreated RMSF. Although correct diagnosis of RMSF requires laboratory testing, 26% of providers stated that they always or almost always treat RMSF without laboratory testing. Fortunately, most providers were aware that RMSF is common in their region and that the condition should still be considered if the patient does not recall a tick bite.

Doctors practicing emergency medicine, internal medicine, and family medicine; and nurse practitioners, physician assistants, and providers practicing for less than 20 years demonstrated less knowledge regarding RMSF. Thus, providers with more education and experience were more knowledgeable of RMSF. The authors suggested targeted educational campaigns about RMSF, particularly focused on the need to treat patients less than age 8 with doxycycline.

Suggested reading: Rocky Mountain Spotted Fever: History of a Twentieth-Century Disease

Reference: Mosites E, Carpenter LR, McElroy K, Lancaster MJ, Ngo TH, McQuiston J, Wiedeman C, Dunn JR. (2013). Knowledge, Attitudes, and Practices Regarding Rocky Mountain Spotted Fever among Healthcare Providers, Tennessee, 2009.Am J Trop Med Hyg. 88(1):162-6.

Individual Medical Insurance: Making the Right Choice

Beginning on January 1, 2014, most Americans will be required to have individual medical insurance. For those who are not currently insured and for those whose employers decide to drop their health insurance coverage, they will need to decide how to pick an insurance company that best meets their personal and family needs. 

One feature that is helpful to look for is whether the health insurance company allows you to lock in the rate for an extended period of time (e.g., one to three years). This is important, because insurance companies can raise their rates during the year. The trade-off is that you are paying a modest amount more initially to lock in the guaranteed rate. Another useful feature is whether the plan offers supplemental cancer coverage and critical illness coverage which can both help protect you from expenses that are not covered by the primary insurance company. Thus, it is very important to understand the annual coverage limits of the primary insurance company when signing up and if you have the option of buying more coverage if needed. It is also important to know if the insurance pays for prescription drug coverage and diagnostic testing.

Lastly, it is also important to understand the distinction between an HMO (health maintenance organization) or a PPO (preferred provider organization). In an HMO insurance plan, you will receive all or most of your care from a provider contracted with the insurance company and it is required for a primary care physician (PCP) to coordinate your healthcare by making referrals to other in-network providers. In a PPO, the insurance plan contracts with a network of health care providers from who you can chose, it is not required to select a PCP, and you can make appointments with specialists without a referral (unless the specialist has a policy requiring this). In a PPO, you can chose a provider outside of the network, but this will likely cost more. Generally speaking, PPOs are the better option due to the added flexibility they provide.

Childhood Tumors: How PET/CT Scans Can Help

When patients are evaluated for a possible tumor, the types of scans they hear about most often are CT (computerized tomography) scans and MRI (magnetic resonance imaging) scans. CT scanning is an advanced imaging technique that uses x-rays and computer technology to produce more clear and detailed pictures than a traditional x-ray. MRI scans produce extremely detailed pictures of the inside of the body by using very powerful magnets and computer technology.

CT scans and MRI scans are known as structural scans because they provide important information about the structure of the body. However, these scans do not provide information about how the area that is pictured actually functions.

There are other types of scans known as functional imaging scans which do provide this important information about function. One such imaging technique is known as a PET scan. A PET scan involves injecting the patient with a small radioactive chemical and being placed in a machine that detects and records energy given off by the substance. The computer translates the energy into 3D pictures which provides information about how cells in the body are functioning because normal cells react differently to the chemical than healthy cells. One type of chemical injected is known as FDG (fluorodeoxyglucose), which is a type of radioactive glucose. When a PET scan uses this substance, it is known as FDG PET.

One problem with functional imaging scans is that they do not provide good information about structure. This problem is solved by combining PET scan data with CT scan data, so that functional imaging data can be superimposed on structural imaging scans. When PET and CT scan data are combined, this is known as PET/CT and can be used to scan the entire body.

In the current issue of the American Journal of Roentgenology, researchers in Toronto, Canada, examined whether FDG PET/CT could reliably differentiate malignant (cancerous) tumors from benign (non-cancerous) tumors in 21 children (13 girls, 8 boys). Tumors are abnormal masses of tissue that form when cells in a certain area of the body reproduce at an increased rate.

The question of whether FDG PET/CT can do this is important because by itself, FDG accumulation can occur in benign masses as well as malignant masses during PET scans. To solve this problem, measuring cell uptake of FDG at two time points (instead of one) is performed, which is known as dual-time imaging. The reason this is done is because FDG is absorbed differently over time in benign and malignant processes. Essentially, malignant lesions will show an increase in FDG uptake (absorption) over time whereas benign areas will remain stable. The uptake of FDG glucose is known as the standardized uptake value (SUV).

In the study reference above, scan 1 was performed 60 minutes after FDG injection. Scan 2 was performed about 2 hours after the first scan. In children with malignant disease, the results showed that the average SUV increased from 7.3 to 10.9 between the two time points. In children with benign masses, the average SUV changed from 4.5 to 4.2 between the two time points. The researchers concluded that dual time point FDG/PET CT is useful in distinguishing malignant disease from benign processes in pediatric patients.

Suggested reading: Happily Hungry: Smart Recipes for Kids with Cancer

Related blog entry: Ovarian Tumors in Children: They Happen

Reference: Costantini DL, Vali R, Chan J, McQuattie S, Charron M. (2013). Dual-Time-Point FDG PET/CT for the Evaluation of Pediatric Tumors. AJR Am J Roentgenol. Feb;200(2):408-13

Chronic Pain: Know the Causes and Risks

All of us have experienced pain of some form in our lives; whether it was the slight bruises of childhood or a stomach ache, we know the feeling. But chronic pain is a slow eater that most of us are unaware of. Unlike the temporary/acute form of pain, chronic pain can be devastating and life changing.

Chronic pain does not attack anyone in a certain age group or in a specific medical condition. It can become a liability on anyone. Untreated pain (and other untreated symptoms) can grow into a fierce form of chronic pain that can put a lot to risk.

Any physical trauma ranging from an injury to an illness can become a chronic nuisance if not treated on time. Chronic pain is any pain that lasts for months or years, and does not necessarily remind one of an untreated medical condition. The pain can be experienced in two situations: after treating an injury e.g. arm pain after treatment of an arm fracture, or due to some uncured (or probably unidentified) illness. The latter form is rather alarming and beckons for immediate attention.

Chronic pain must be probed immediately for its cause, as it can be associated to serious conditions like arthritis or cancer. In some cases, the pain might not have any origin at all; it could be a chronic muscular pain.

The most common cause is an injury that took place in an accident or even something like carpal tunnel. No matter what the case, the pain can be excruciating and majorly affect the person’s lifestyle.

In all instances, the pain must never go untreated. Immediately consult a medical facility to get advice from pain management doctors and chronic pain experts. You will be given advice on how to control the chronic pain, and eliminate it completely. Just how the pain takes months to become a permanent pest in your body, it will take some time to go away.

Treatment of chronic pain is not very effortless; apart from pain-relieving medication you will need to alter your lifestyle to make it healthier. Doctors suggest exercises, yoga, meditation, balanced diets and even acupuncture for pain treatments. A healthy lifestyle will help the body stay in shape, and combat the causes of pain more efficiently.

Those suffering from chronic pain also suffer from emotional distress, anxiety, insomnia, and even immobility. The pain can greatly affect a person’s quality of life and morale, causing long-term depression to seep in and create further problems. In more severe cases, patients might need to consult an emotional therapist in order to come back to normal life.

Untreated pain can have severe physical and emotional consequences. Never leave a pain treatment for tomorrow; you never know what might be causing the pain in the first place. In most cases, it is the non-drug treatments and lifestyle improvement that make the most difference. Treat pain before it becomes chronic and almost invincible; the sooner the better!

The above post is a guest blog post.

A New Technique to Treat Foot Infections in Diabetes

Diabetes mellitus is a complex, chronic disorder in which the body is not able to effectively use a natural chemical called insulin. Insulin's main job is to quickly absorb glucose (a type of sugar) from the blood into cells for their energy needs and into the fat and liver cells for storage.

Because of this, high sugar levels can occur in people with diabetes which can damage the body. For example, people with diabetes are more prone to infections because high levels of sugar in the blood make it more difficult for the body to fight against infections.

One common area where infections are likely to occur in diabetes is the feet. This is because the accumulation of sugar can damage nerve fibers in the feet, causes decreased sensation, and poor blood circulation. This makes the feet more prone to ulcers (open sores), infection, and eventually gangrene (tissue death due to poor blood supply or infection of a wound). In the worst case scenario, this can lead to amputation of the foot or feet to prevent a more widespread and potentially deadly bodily infection.

When diabetic foot complications arise, they can be difficult to manage and treat because people with diabetes often have other medical diagnoses (e.g., kidney problems, heart problems) that make it more difficult to maintain adequate levels of antibiotic medication at the site of infection without causing harmful effects (e.g., organ damage) on the body as a whole. This can lead to ineffective treatment.

As a result of this problem, new methods are needed to deliver targeted antibiotics to the infected limb for extended periods while limiting harmful effects on the rest of the body. In the current issue of the American Journal of Translational Research, researchers reported success for the first time with a new non-surgical technique designed to accomplish exactly that and the hope is that this can be applied to humans, particularly those with diabetic foot infections.

In the study, the hind limb of 11 sheep was treated with an antibiotic named Gentamicin using one of two methods. The first method was standard intravenous administration to 6 sheep, as would typically occur in a hospital. The second method was a technique known as a percutaneous recirculation circuit. As the name implies, this technique involves establishing a circuit of blood supply by inserting a catheter (flexible plastic tube) in the femoral vein (large vein in the leg) and femoral artery (large artery in the leg). An artery carries blood away from the heart, whereas a vein carries blood to the heart.

The system caught the venous return of blood via the catheter, re-oxygenated it with a special device known as a membrane oxygenator, and returned it to the femoral artery with a special pump called a roller pump. In this way, when medication was administered via this system, it was kept more localized to the hind limb.

To test how much Gentamicin was in the hind limb, tissue samples of the back limb were taken, which included bone, skeletal muscle, and synovial (joint) fluid 30 to 60 minutes after the medication was administered. After the 60-minute point, the animals were euthanized and samples of the liver, kidney, and lung were taken to determine how much Gentamicin was present.

The results of the study showed that there was a significantly greater amount of Gentamicin in the bone, skeletal muscle, and joint fluid of those receiving Gentamicin via the circuit method versus compared to the standard intravenous method.  In fact, there was 10 times the amount of Gentamicin found in the joint fluid, which the authors stated could serve as a reservoir for longer effectiveness. With the circuit system, there was a non-significant amount of Gentamicin found in the liver, lung, and kidney. The difference in antibiotic levels in these organs was not significantly different between the two groups but there was a trend for less antibiotic levels in these organs with the circuit method.

The authors concluded that the circuit method is a safe and effective non-surgical method to deliver a greater amount of antibiotic to the affected limb without causing greater harm to the rest of the body. The authors stated that this method may be directly useful for patients with diabetes who are at high risk of tissue or limb loss due to infections that are otherwise non-responsive to treatment.

Suggested reading: The End of Diabetes: The Eat to Live Plan to Prevent and Reverse Diabetes

Reference: Byrne, M., Idrizi, R., Power, J., Kaye, D. (2013). Percutaneous re-circulating isolated limb perfusion of gentamicin in a large animal model: targeted delivery of gentamicin to limb. Am J Transl Res, 5(1):47-52

Is Your Drinking Water Contaminated by Utility Poles?

These days, many people purchase bottled spring water, bottled filtered water, and/or have their own water filtration system attached to their faucet. This is partly due to improved taste perceptions but is also often due to fears of water contamination. While public water is usually safe to drink there are always exceptions. The risks are increased with private well water.

In the most recent issue of the American Journal of Public Health, researchers described two scenarios of private drinking water being contaminated from utility poles treated with pentachlorophenol (PCP). PCP is a chemical that is used as a wood preservative to coat utility poles in the U.S. This helps utility poles last for 35 years as opposed to 7 years when untreated. PCP is also used as a pesticide and disinfectant and is also used as a wood coating for railroad ties.

PCP is known to be highly toxic and can degrade slowly in the environment (taking up to 5 years depending on the bacteria present in the soil). It can cause harm to the body by short-term exposure to high levels or from long-term exposure to low levels. PCP can damage multiple organs and body systems such as the brain, kidneys, and liver. It can also poison the blood and is known to be carcinogenic (cancer causing).

In the U.S., PCP levels in the water supply must be measured by water companies and disclosed to the public if it exceeds a certain level (0.001 milligrams per liter). A milligram is one thousandth of a gram so only a very small amount of PCP is allowed in water.

In the study in the American Journal of Public Health, two scenarios in Vermont were described in which private drinking water was contaminated by PCP from utility poles. Specifically, two people called the Vermont Health Department due to chemical-like (e.g., gasoline smell) smell in their drinking water, one from a shallow dug well and another from a private spring. In the first case, the cause was determined to be a utility pole coated with PCP that was likely in contact with the water table. In the second case, the cause was three new utility poles placed by a private spring. Both people were advised to avoid contact with the water.

When the water was tested, the PCP level was 2.06 milligrams per liter in the first case (2000 times the accepted level) and 0.007 milligrams per liter in the second case. In both cases, the utility company replaced the PCP poles with non-treated cedar poles. In the first case, a new well was dug. In the second case, a filtration system was put in place. The water then tested negative for PCP in each case.

Interestingly, the authors note that environmental regulations do not apply to PCP treated poles. For example, while the Environmental Protection Agency can regulate the sale and use of pesticides, there is an exemption if pesticides are used as a protective treatment. The authors recommended better utility pole placement guidelines (e.g., not near wells), using non-treated poles, cement/metal poles, or less toxic wood treatments, and removing legal exemptions for utility poles.

Suggested reading: The Drinking Water Book: How to Eliminate Harmful Toxins from Your Water

Reference: Karlsson L, Cragin L, Center G, Giguere C, Comstock J, Boccuzzo L, Sumner A. Am J Public Health. (2013). Pentachlorophenol Contamination of Private Drinking Water From Treated Utility Poles. 103(2):276-277.

Preventing Post-Partum Depression in Adolescent Mothers

Post-partum depression (PPD) is a type of depressive disorder that occurs in a parent after childbirth, although it usually occurs in the mother. It is a fairly common problem, with prevalence rates estimated to be as high as 25%.

Signs and symptoms include but are not limited to frequent crying, sadness, irritability, anxiety, social avoidance, tiredness, sleep disturbance, appetite changes, disinterest in the infant, and fear of being left alone with the infant.

PPD onset occurs within 4 weeks after childbirth but usually begins about two weeks after childbirth. The depression typically lasts between several months and 12 months.The cause of PPD is not well understood, although several possible causes in mothers include hormonal changes, vitamin deficiency, lifestyle changes, or a response to inadequate social support. However, there are contradictory studies supporting and refuting some of these hypotheses.

There are numerous treatments available for PPD which include medication, psychological counseling (individual and/or group), dietary changes, and behavioral changes (e.g., improved sleep routine). However, the ideal situation is to prevent PPD from occurring in the first place. Presently, methods of preventing PPD include educating pregnant women about the risks of PPD, proper exercise, and a nutritious diet.

In an upcoming study published in the American Journal of Obstetrics & Gynecology, researchers in Rhode Island reported on the results of a randomized controlled trial to study the effectiveness of a psychological intervention to prevent postpartum depression in adolescent mothers (13 to 17 years old at time of conception) who were pregnant for the first time.

There were 106 mothers in the study. Subjects were not included if they had prior treatment for a mental health disorder or current evidence of an emotional disorder, substance abuse, or psychosis (disengagement from reality). In terms of race, 53% of mothers were Hispanic, 17% were black, and 16% were white.

Of the 106 mothers, 54 were randomly assigned to a new intervention program and 52 (the control group) were assigned to a standard educational program. The new intervention program was known as REACH (Relaxation, Encouragement, Appreciation, Communication, and Helpfulness) and is specifically geared towards adolescents.

REACH is based in a type of therapy known as interpersonal therapy. As such, the program teaches communication strategies to better manage conflicts before and after delivery, how to manage stress, education about motherhood and depression, how to develop a healthy social support system and relationships, how to set realistic goals, and educating the mother about psychosocial resources. All mothers (in the REACH group) and the control group, were provided with the book Baby Basics: Your Month By Month Guide to a Healthy Pregnancy. However, the control group was not provided with access to the material from the REACH program.

The programs took place before delivery of the infant. Each program took place once a week for five weeks with the session length being 30 to 60 minutes. The mothers were monitored at 6 weeks, 3 months, and 6 months after delivery to monitor for depression. The overall results showed that mothers receiving the REACH intervention had half the rate of depression (12.5%) than mothers receiving the non-REACH control program (25%), supporting the usefulness of the REACH intervention.

Suggested reading: Postpartum Depression For Dummies

Related blog entries: Anti-depressants in Pregnancy: What are the Risks?

Reference: Phipps MG, Raker CA, Ware CF, Zlotnick C. (2013, in press). Randomized controlled trial to prevent postpartum depression in adolescent mothers. Am J Obstet Gynecol.

Klinefelter Syndrome: An Underdiagnosed Genetic Disorder

Each person has 23 pairs of chromosomes (46 in total). One of each pair of chromosomes is inherited from the mother and one of each pair is inherited from the father. The 23rd pair of chromosomes is involved in determining gender. The 23rd pair of chromosomes consist of X and/or Y chromosomes.

As the names imply, an X chromosome is shaped like an X, whereas a Y chromosome is shaped like a Y. If a person has two X chromosomes, the person will develop as a female. If a person has an X and a Y chromosome, the person will develop as a male.

In Klinefelter syndrome, the male has at least one extra X chromosome which is why it is known as XXY syndrome or 47,XXY (since there are 47 chromosomes). Because of the extra X chromosome, Klinefelter patients can present with more feminine features such as less hair on the face, armpits, and groin and less masculine features such as small testes which makes it the most common genetic cause of infertility. Many Klinefelter patients tend to be tall with abnormal body proportions. The more X chromosomes present, the more of these abnormal bodily features for males tend to be present.

Klinefelter syndrome is believed to be present in 1 out of every 500 to 1000 male births. While some patients with Klinefelter syndrome show some of signs noted above, the only way to definitely diagnose the condition is by genetic testing.

Klinefelter syndrome is incurable. It is treated with testosterone supplementation at birth (if identified then), which can help normalize body proportions and yield more body hair but it does not treat infertility. Psychological counseling is sometimes used to treat depression and anxiety that results from feeling different. Early identification of Klinefelter syndrome can also help better understand the learning difficulties known to occur in the condition, which typically involves decreased verbal abilities.

In a recent article published in the American Journal of Medical Genetics Part C (Seminars in Medical Genetics), researchers in Denmark published age specific recommendations for medical management in four ranges: ages 0-2, ages 3-10, puberty, and adulthood summarized in a helpful and easy to use table. It is particularly important for health care providers to be more aware of Klinefelter syndrome and these age specific treatment recommendations because as the researchers note, the condition is highly undiagnosed (75% undetected) with only 10% of cases diagnosed before puberty. Typically, Klinefelter syndrome is diagnosed in adulthood during evaluations for infertility. This is troubling because as noted previously, early detection and treatment can improve the lives of these patients.

Suggested reading: Living with Klinefelter Syndrome
 
Reference: Aksglaede L, Link K, Giwercman A, Jørgensen N, Skakkebaek NE, Juul A.(2013). 47,XXY Klinefelter syndrome: Clinical characteristics and age-specific recommendations for medical management. Am J Med Genet C Semin Med Genet.163(1):55-63

Fetal Alcohol Syndrome or Not? The Shocking Results

Fetal alcohol spectrum disorder (FASD) is a broad term which refers to birth defects in the fetus caused by high maternal levels of alcohol consumption during pregnancy. A fetus is a developing human that is inside the mother from the end of the 8th week to birth. There are numerous FASD subtypes, the most common of which is fetal alcohol syndrome (FAS).

FAS, which was first described in 1968, is a pattern of mental and physical deficits that involves specific facial abnormalities (e.g., small eye openings, thin upper lip), growth failure, and is the leading cause of mental retardation in the Western world. For patients who do not meet full criteria for FAS (e.g., have slight facial abnormalities, normal growth) a diagnosis of partial FAS can be given. Some use the terms fetal alcohol effects, alcohol-related birth defects, and alcohol-related neurodevelopmental disorder but each have been sources of controversy.

Diagnosis of FASD relies on clinical coding system criteria but there are no objective biomarkers (e.g., blood test results, imaging findings) to confirm the diagnosis. As a result, the condition can be over-diagnosed.
Children presenting with signs of FASD are sometimes referred for genetic testing during the course of a diagnostic evaluation to determine is there may be another explanation for the patient’s presentation although this is not routinely done. In a recent article in the American Journal of Medical Genetics: Part A, researchers from The Netherlands evaluated 27 children referred to a genetics department between 2005 and 2010 who were suspected of having FASD. The results may surprise you.

First, when the researchers applied the most widely used coding systems for FASD based on clinical criteria (e.g., facial abnormalities, growth abnormalities), they found that more than half of the children did not meet criteria for FASD. Even more interesting is that 30% of the children appeared not to have confirmed prenatal alcohol exposure. Two of these children were found to have abnormal microstructural rearrangements of chromosomes (structures that contain genes). Genetic testing also found that in 92% of children had factors other than prenatal alcohol exposure that could have affected their intellectual functioning, such as social deprivation and intellectual disabilities inherited from family members.

The lesson from this study is that things are not always as they seem and that clinicians need to think critically when evaluated cases of suspected FASD. This includes referral for genetic testing.

Suggested reading: A Mother's Story of Raising a Child with Fetal Alcohol Syndrome
 
Reference: Abdelmalik N, van Haelst M, Mancini G, Schrander-Stumpel C, Marcus-Soekarman D, Hennekam R, Cobben JM. (2013). Diagnostic outcomes of 27 children referred by pediatricians to a genetics clinic in the Netherlands with suspicion of fetal alcohol spectrum disorders. Am J Med Genet A. 161(2):254-60.