Monday, August 20, 2007

Posttraumatic Stress Disorder and Pregnancy Health

Posttraumatic Stress Disorder and Pregnancy Health: Preliminary Update and Implications

Leslie Morland, Psy.D., Deborah Goebert, D.P.H., Jane Onoye, Ph.D., LeighAnn Frattarelli, M.D., Chris Derauf, M.D., Mark Herbst, M.D., Courtenay Matsu, M.D., and Matthew Friedman, M.D., Ph.D.
From the Dept. of Psychiatry, John A. Burns School of Medicine, Univ. of Hawaii; the National Center for PTSD, Pacific Island Division, VA Pacific Island Healthcare System; the Dept. of Obstetrics, Gynecology, and Women’s Health, John A. Burns School of Medicine, Univ. of Hawaii; the Dept. of Pediatrics, John A. Burns School of Medicine, Univ. of Hawaii, and the National Center for PTSD, Executive Division, White River Junction, VT.

Posttraumatic stress disorder (PTSD) is pervasive among women of childbearing age.

The cascade of behavioral health and neuroendocrine changes commonly associated with PTSD may adversely affect perinatal health.

The authors examined the relationship between PTSD and perinatal health in a sample of 101 women seeking prenatal care on the island of Oahu, Hawaii.

Trauma, PTSD, and psychological and behavioral health were assessed during prenatal care. Pregnancy health, labor and delivery information, and birth outcomes were abstracted from medical records post-partum.

Findings suggest that women with PTSD entering pregnancy are at increased risk for engaging in high-risk health behaviors, such as smoking, alcohol consumption, substance use, poor prenatal care, and excessive weight gain.

Authors discuss clinical and research implications. Full Text

Psychosomatics 48:304-308, August 2007

Friday, August 17, 2007

Green tea protected cancerous bladder cells

Green tea may protect the bladder from becoming inflamed

Herbal agents could be used to treat inflammatory bladder diseases, according to a preliminary study that looked at the ability of green tea to protect bladder cells from inflammation. The University of Pittsburgh School of Medicine study, being presented at the annual meeting of the American Urological Association (AUA) in Anaheim, Calif., found that components of green tea protected bladder cells from damage in culture. The study is Abstract 299 in the AUA proceedings.

Green tea, reported to have many health benefits, is rich in powerful antioxidants that make it a possible remedy for many medical conditions. It is comprised of catechins - plant metabolites that provide it with many anti-oxidative properties.

"We discovered that catechins found in green tea protected both normal and cancerous bladder cells from inflammation when we exposed the cells to hydrogen peroxide," said Michael B. Chancellor, M.D., professor of urology and gynecology at the University of Pittsburgh School of Medicine. "Although further studies are needed, these results indicate herbal supplements from green tea could be a treatment option for various bladder conditions that are caused by injury or inflammation."

In the study, normal and cancerous bladder cells were exposed to two major catechin components of green tea, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), for 23 hours. Both significantly protected cell lines from exposure to hydrogen peroxide, which damages or kills cells. The concentrations of EGCG and ECG used in the study were at levels that may be achieved through dietary intake.

University of Pittsburgh Schools of the Health Sciences

Thursday, August 16, 2007

Green tea: Protect against autoimmune disease

Green tea may help prevent autoimmune diseases

Green tea may help protect against autoimmune disease, Medical College of Georgia researchers say.

Researchers studied an animal model for type I diabetes and primary Sjogren's Syndrome, which damages the glands that produce tears and saliva.

They found significantly less salivary gland damage in a group treated with green tea extract, suggesting a reduction of the Sjogren's symptom commonly referred to as dry mouth. Dry mouth can also be caused by certain drugs, radiation and other diseases.

Approximately 30 percent of elderly Americans suffer from degrees of dry mouth, says Dr. Stephen Hsu, a researcher in the MCG School of Dentistry and lead investigator on the study. Only 5 percent of the elderly in China, where green tea is widely consumed, suffer from the problem.

"Since it is an autoimmune disease, Sjogren's Syndrome causes the body to attack itself and produce extra antibodies that mistakenly target the salivary and lacrimal glands," he says.

There is no cure or prevention for Sjogren's Syndrome.

Researchers studied the salivary glands of the water-consuming group and a green tea extract-consuming group to look for inflammation and the number of lymphocytes, a type of white blood cells that gather at sites of inflammation to fend off foreign cells.

The group treated with green tea had significantly fewer lymphocytes, Dr. Hsu says. Their blood also showed lower levels of autoantibodies, protein weapons produced when the immune system attacks itself, he says.

Researchers already know that one component of green tea - EGCG - helps suppress inflammation, according to Dr. Hsu.

"So, we suspected that green tea would suppress the inflammatory response of this disease. Those treated with the green tea extract beginning at three weeks, showed significantly less damage to those glands over time."

These results, published in a recent issue of Autoimmunity, reinforced findings of a 2005 study showing a similar phenomenon in a Petrie dish, Dr. Hsu says.

Researchers also suspect that the EGCG in green tea can turn on the body's defense system against TNF-alpha - a group of proteins and molecules involved in systemic inflammation.

TNF-alpha, which is produced by white blood cells, can reach out to target and kill cells.

"The salivary gland cells treated with EGCG had much fewer signs of cell death caused by TNF-alpha," Dr. Hsu says. "We don't yet know exactly how EGCG makes that happen. That will require further study. In some ways, this study gives us more questions than answers."

Further study could help determine green tea's protective role in other autoimmune diseases, including lupus, psoriasis, scleroderma and rheumatoid arthritis, he says.

Medical College of Georgia

Wednesday, August 15, 2007

SIDS: association with lethal arrhythmias

Heart rhythm genes possible factors in SIDS

Nearly 10 percent of sudden infant death syndrome (SIDS) victims have mutations or variations in genes associated with potentially lethal heart rhythms (arrhythmias), according to two newly published studies involving Vanderbilt researchers.

The findings indicate that arrhythmia-susceptibility genes represent important genetic contributors to SIDS, said Alfred L. George Jr., M.D., senior author on one of the studies. The studies appear in the early online edition of the journal Circulation.

According to the Centers for Disease Control and Prevention, approximately 2,200 deaths each year in the United States are attributed to SIDS, making it the third leading cause of death among all infants, but the leading cause of mortality in infants age 1 month to 1 year. Several behavioral and environmental factors - such as prone (stomach) sleeping position and exposure to cigarette smoke - are known risk factors. Campaigns to educate parents about these potential dangers may explain the decrease in SIDS since the early 1990s.

However, SIDS continues to be a leading cause of infant mortality in developed countries, and the underlying basis of the condition remains unclear. A popular theory proposes that SIDS occurs because of a combination of risks including abnormal physiological state, environmental factors and developmental vulnerabilities. Genetic factors have also been proposed to be important.

"SIDS is not one disease," said George, the Grant W. Liddle Professor of Medicine and director of the Division of Genetic Medicine. "Multiple conditions can increase the risk of sudden death in an infant. Some have been identified, but many have not."

Anecdotal evidence previously suggested that some SIDS victims carry mutations in genes associated with conditions such as the long QT syndrome (LQTS) that predispose individuals to life-threatening arrhythmias and sudden death. But the proportion of SIDS cases that carry such mutations was not clear.

George's collaborators, Peter Schwartz, M.D., in Italy, and Torleiv Rognum, M.D., Ph.D., in Norway, led the efforts to screen seven arrhythmia-associated genes in 201 SIDS cases from Norway - the largest ever genetic survey of a SIDS cohort. The results showed that 9.5 percent of SIDS victims harbored mutations in genes associated with inherited forms of cardiac arrhythmia, such as LQTS.

The researchers identified mutations and variations in several genes, including the gene that encodes the cardiac sodium channel - a protein that regulates the electrical properties of heart cells. George's lab then performed studies to understand the physiological consequences of mutations in the cardiac sodium channel gene, called SCN5A, which has previously been associated with LQTS and several other conditions that cause unstable heart rhythms and sudden death.

"We observed a pattern of SCN5A dysfunction that is reminiscent of what's been observed in LQTS. That gives us confidence that the mutations observed in SIDS victims are not benign genetic variants - but rather could increase the risk of potentially lethal arrhythmias," he said. The researchers have similar evidence, to be published separately, demonstrating that mutations in heart potassium channels are also contributing factors in SIDS.

The findings also suggest that there may be strategies to identify whether infants are a carrier of one of these mutations before the tragic event of their death, George said.

"We are not recommending that a population-wide genetic screening be done, but there may be simpler, cost-effective measures that should be investigated further, perhaps performing ECG (electrocardiogram) screening of infants, although this idea is controversial."

Inherited arrhythmias are manageable conditions that can be treated with medications or implantable devices, George said.

"There's potentially an infant death every other day in the U.S. due to this problem (arrhythmias)," he said. "Exactly how best to identify this risk and prevent arrhythmia-related death during infancy needs to be determined."

George and colleagues are continuing to analyze other arrhythmia-linked genes identified in the Norwegian SIDS cohort. They are also planning studies to determine if the parents of SIDS victims carry the same mutations.

"This is critical because knowing how often mutations are transmitted from parents rather than occur spontaneously, will help establish the risk to siblings of SIDS victims," he said.

George hopes that eventually, all of the causes of SIDS - environmental, developmental and genetic factors - will be identified.

"Many years from now, 'SIDS' may not be a term we use anymore because we will understand all causes of sudden infant death," George said. "But right now, SIDS is a bona fide disease category, and we should strive to understand it fully."

Vanderbilt University Medical Center

Tuesday, August 14, 2007

SIDS - Preventative measures

New study finds infant hearing test results may predict sudden infant death syndrome

One of the greatest medical mysteries of our time has taken a leap forward in medical understanding with new study results announced by Dr. Daniel D. Rubens of Children's Hospital and Regional Medical Center in Seattle. Rubens' study published in July, 2007 in Early Human Development found all babies in a Rhode Island study group who died of Sudden Infant Death Syndrome (SIDS) universally shared the same distinctive difference in their newborn hearing test results for the right inner ear, when compared to infants who did not have SIDS. This is the first time doctors might be able to identify newborns at risk for SIDS by a simple, affordable and routine hearing test administered shortly after birth. In the study, medical records and hearing tests of 31 babies who died from SIDS in Rhode Island were examined and compared to healthy babies. Rhode Island has a particularly robust database of newborn hearing test data.

The cause of SIDS, known around the world as "crib death" and "cot death," has eluded physicians and grieving parents for centuries. Responsible for many previously unexplainable deaths of infants usually two to four months old and striking boys more than girls, SIDS causes tragic, sudden death in approximately 1 in 1,000 newborns world-wide, making it the largest cause of death in young infants. In the United States approximately 3,600 deaths each year were attributed to SIDS from 1992-1999, according to an April, 2004 article in Archives of Pediatric and Adolescent Medicine. Death occurs during sleep, seemingly with no warning and no previous symptoms. Changes in infant care have been promoted including the "Back to Sleep" program discouraging sleeping on the stomach, and avoiding exposure to cigarette smoke. Various causes have been suggested, including disturbances in respiratory control and infant overheating, but to date nothing has proven conclusive.

It is known that the inner ear contains tiny hairs that are involved in both hearing and vestibular function. Rubens proposes that vestibular hair cells are important in transmitting information to the brain regarding carbon dioxide levels in the blood. He postulates that injury to these cells will disrupt respiratory control, playing a critical role in predisposing infants to SIDS.

The SIDS infants in Rubens' study showed a consistent four point lower score in their standard newborn hearing tests, across three different sound frequencies in the right ear, when compared to babies that didn't die from SIDS. Additionally, healthy infants typically test stronger in the right ear than the left. However, in each of the SIDS cases studied, the right ear tested lower than the left, reversing the test results of healthy babies.

"This discovery opens a whole new line of inquiry into SIDS research," said Rubens. "For the first time, it's now possible that with a simple, standard hearing test babies could be identified as at risk for SIDS, allowing preventative measures to be implemented in advance of a tragic event." He urges further research, adding "We must now fully explore all aspects of inner ear function and SIDS, and analyze testing frequencies higher than those currently tested by newborn hearing screen centers."

Previous groundbreaking SIDS research at Seattle Children's Hospital and Regional Medical Center took place during the 1970's, when Dr. Bruce Beckwith was one of the first researchers to describe features of SIDS that can identify cases during autopsy, distinguishing SIDS deaths from other causes of infant death. Beckwith is highly recognized in the body of SIDS research, making his work among the most significant earlier published findings about the condition. "It has been my great privilege to follow in Dr. Beckwith's footsteps with this new discovery that creates the possibility of identifying SIDS infants before tragedy strikes," said Rubens. "Each new breakthrough brings us closer to making SIDS a condition of the past."

Children's Hospital and Regional Medical Center of Seattle

Friday, August 10, 2007

Erectile dysfunction: Reducing the risk

Prevent smoking to reduce risk of erectile dysfunction

Men who smoke cigarettes run an increased risk of experiencing erectile dysfunction, and the more cigarettes smoked, the greater the risk, according to a study by Tulane University researchers published in the American Journal of Epidemiology.

A team of researchers led by Jiang He, Professor of Epidemiology at the Tulane University School of Public Health and Tropical Medicine, examined the association between cigarette smoking and erectile dysfunction in a 2000-2001 study in China involving 7,684 men. The researchers used questionnaires to assess the status of cigarette smoking and erectile dysfunction. Those surveyed were men between the ages of 35-74 who did not have vascular disease.

The team found that there was a significant statistical link between the number of cigarettes that men smoked and the likelihood they would experience erectile dysfunction. The association between smoking and erectile dysfunction was even stronger in participants with diabetes. An estimated 22.7 percent of erectile dysfunction cases among Chinese men might be attributable to cigarette smoking, says the study.

Although erectile dysfunction is not a life-threatening condition, it compromises well-being and quality of life. The Tulane study results suggest that smoking prevention should be an important approach for reducing the risk of erectile dysfunction.

Tulane University

Wednesday, August 08, 2007

Milk and butter may help prevent asthma

Full fat milk and butter may help prevent asthma

Young children who regularly eat products containing milk fat are less likely to develop asthma, concludes a study in Thorax.

Researchers assessed the food consumption of 2,978 Dutch children aged 2 years and related this to asthma symptoms at age 3.

Asthma at age 3 was lower in children who consumed full cream milk and butter daily than in those who did not. Similarly, wheeze was lower in children who consumed milk products (including yoghurt and chocolate milk) and butter daily than in those who did not. Daily consumption of brown bread was also associated with lower rates of asthma and wheeze.

Children who consumed fruit juice and vegetables daily had lower asthma rates than other children, but these differences were not statistically significant.

These results provide evidence for a beneficial association between daily consumption of products containing milk fat and the development of asthma and wheeze in young children, say the authors. Various components of the products involved could play a role, such as different fatty acids, but also antioxidants or other micronutrients, they suggest.

British Medical Journal (BMJ)

Monday, August 06, 2007

Hyperthyroidism - Clinical Features

Clinical Features and Associated Disorders
Although new-onset adulthood seizures are rarely related to hyperthyroidism, the seizure incidence among thyrotoxic patients ranges from 1 to 9 percent. Movement disorders, such as tremor (usually enhanced physiological tremor) and choreoathetosis, as well as upper motor neuron signs, including spasticity, hyperreflexia, clonus, and Babinski's signs, may also be observed.

Peripheral neurological features include cranial and peripheral neuropathies, as well as neuromuscular junction and muscle disturbances . Ocular features include lid lag, stare, widened palpebral fissures, extraocular muscle dysfunction with diplopia, and optic nerve compression with visual impairment.
Eyelid retraction manifests in several ways: (1) Stellwag's sign, a staring expression with infrequent blinking; (2) Dalrymple's sign, a widened palpebral fissure due to retraction of both the upper and lower lids; (3) von Graefe's sign, a larger than normal portion of visible sclera with downward eye movement; (4) Joffroy's sign, a lack of frontalis muscle contraction with upgaze; and (5) Moaubius' sign, sympathetic overactivity-induced exophthalmos with resultant limited convergence.
Although reports of a distal sensorimotor polyneuropathy in thyrotoxic patients are rare, improvement of the neuropathic features with attainment of the euthyroid state indicates that these features are manifestations of hyperthyroidism. Myasthenia gravis (MG) can be associated with hyperthyroidism, although some of the reported cases may have been secondary to coincident MG. Also, when bulbar weakness responds to treatment of the hyperthyroid state, it is more likely related to hyperthyroidism. When MG co-exists with thyrotoxic myopathy, the clinical findings do not differ from those in euthyroid patients, although the patients may be weaker due to the co-existence of two motor disorders. Thyrotoxic myopathy is characterized by the gradual onset of proximal limb weakness, which may be accompanied by myalgias, easy fatigability, and prominent atrophy. Although the muscular atrophy may be severe, most patients remain ambulatory. Shoulder girdle muscles can be more severely affected than the hip girdle muscles, with prominent atrophy and scapular winging. Distal limb muscles are also affected, the facial muscles may be affected, and, rarely, bulbar and ocular muscles are involved.
Thyroid-associated ophthalmopathy refers to the exophthalmos and ocular muscle dysfunction associated with thyroid disease. It is seen in most patients with Graves' disease but is also seen in 5 percent of patients with Hashimoto's thyroiditis. It is not correlated with the onset of Graves' disease, having been reported to precede (rarely), occur concomitantly with, or develop after its treatment. It also does not correlate with the level of circulating thyroid hormone and may occur in euthyroid patients or in patients with hypothyroid Graves' disease. When it is prominent, thyroid-associated ophthalmopathy may cause exposure keratopathy (due to marked proptosis), as well as optic nerve compression. Thyrotoxic periodic paralysis refers to recurrent attacks of flaccid paralysis of the limbs and trunk (the oculobulbar muscles are usually spared or involved to a lesser degree) due to secondary hypokalemia.
Differential Diagnosis.
The differential diagnosis of thyrotoxicosis includes other hypermetabolic disorders, euthyroid hyperthyroxinemia, and nonthyroidal causes. Occasionally, recognition that myopathic features are due to thyrotoxicosis can be difficult, especially if the myopathy is the presenting feature (rare), when exophthalmos is minimal, or when an apathetic state is present. When it is present, the observation of hyperreflexia is helpful, because this feature is not observed in other metabolic myopathies. Thyrotoxic myopathy with pronounced muscular atrophy should be differentiated from progressive muscular atrophy by the presence of fasciculations and more profound weakness in the latter. When thyrotoxic myopathy involves the ocular and bulbar musculature, it must be differentiated from MG. In thyrotoxic myopathy, rapid muscle fatigue and recovery with rest is not appreciated, a response to anticholinesterases is not observed, and decrement is not apparent on EMG; in MG, ocular and bulbar muscle involvement is more pronounced and atrophy is not present. Polymyositis should also be considered and is differentiated by EMG and muscle biopsy.

TFTs can confirm thyrotoxicosis, typically demonstrating an elevated free T4 , total T4 , T3 RU, free thyroxine index (FTI), free T3 , total T3 , and a suppressed (usually undetectable) TSH. A normal or elevated TSH in the face of unequivocal clinical thyrotoxicosis should raise suspicion for a TSH-secreting pituitary adenoma. Other laboratory features may include anemia, hypokalemia, hypercalcemia, and an elevated erythrocyte sedimentation rate. Roughly half of hyperthyroid patients demonstrate EEG changes, most commonly generalized slowing or excessive fast activity, both of which resolve with attainment of the euthyroid state. Magnetic resonance imaging (MRI) with gadolinium may demonstrate the characteristic features of thyroid ophthalmopathy including multiple extraocular muscle (EOM) involvement, smooth margins gradually tapering into the tendon insertions, and uniform enhancement when contrast is administered. These features are readily displayed with fat saturation techniques that de-emphasize intraocular fat. Optic nerve impingement may also be visualized with a similar approach. MRI may also be useful in ruling out orbital pseudotumor, Tolosa-Hunt syndrome, orbital lymphoma, Wegener's granulomatosis, and orbital aspergillosis.
When co-existent MG is considered, acetylcholine receptor antibodies in response to edrophonium (Tensilon) may be helpful in its evaluation. Although the Tensilon test may be normal in MG (false-negative result) and may lead to improvement of dysthyroid orbitopathy (false-positive result), patients with thyrotoxic bulbar features typically do not have immunological, electrophysiological, or pharmacological evidence of MG.
Almost all of the clinical features of thyroid dysfunction, with the exception of thyroid-associated ophthalmopathy, resolve once the euthyroid state is achieved. , Medical treatment of thyrotoxicosis includes the use of beta blockers; antithyroid, anti-inflammatory, and immunosuppressive drugs; radioactive iodine-131; and iodine-containing compounds. Beta blockers, in addition to decreasing the beta adrenergic-mediated features of thyrotoxicosis, may decrease the peripheral conversion of T4 to T3 . Beta blockers are also useful in the prophylactic treatment of TPP while attainment of the euthyroid state is awaited. A typical dosage regimen is propranolol, 40 mg four times daily. In hyperthyroid patients with co-existent MG, beta blockers should be used cautiously because of their neuromuscular blocking properties. Higher grade orbital features typically require either systemic corticosteroids (with or without cyclosporine), irradiation, or orbital decompression, yet some believe surgery is rarely indicated because the dysthyroid orbitopathy usually spontaneously arrests before a serious degree of ophthalmopathy has been reached. One of the most frequent complications of thyroid surgery is recurrent laryngeal nerve paralysis. A more limited surgery involving partial lid suturing may be required to protect the cornea.

Sunday, August 05, 2007



Pathogenesis and Pathophysiology

Thyroid hormones affect mitochondrial oxidative capacity, protein synthesis and degradation, tissue sensitivity to catecholamines, muscle fiber differentiation, and capillary growth. Excess thyroid hormone produces accelerated muscle protein catabolism and enhanced lysosomal protease activity, and interferes with the anabolic effects of insulin on muscle. Despite this understanding, the exact pathophysiology of thyrotoxic myopathy remains unknown. CNS observations include elevated rates of cerebral circulation, faster posterior dominant rhythms, alterations in the sensitivity of some brain enzymes and neurotransmitter systems, and altered metabolic responses. At present, the specific pathophysiological processes causing these manifestations remain unknown. It has been proposed that alterations in central and peripheral beta-adrenergic tone may be responsible for hyperthyroid-related tremor and chorea, and that brisk tendon reflexes may reflect faster muscle contraction and relaxation times.

Epidemiology and Risk Factors

Hyperthyroidism is more common in women than in men (10:1 ratio) and often shows a strong familial predisposition. During pregnancy, hyperthyroidism occurs more commonly than hypothyroidism, with an incidence ranging from 0.05 to 0.2 percent, most commonly related to Graves' disease, acute (i.e., subacute) thyroiditis, toxic nodular goiter, and toxic adenoma. The incidence of low-birth-weight infants is significantly increased, and neonatal mortality is slightly increased.

Clinical Features and Associated Disorders

The general clinical features of thyrotoxicosis:
Subjective - Impaired concentration and memory, emotional lability, nervousness, irritability, palpitations, heat intolerance, increased sweating and appetite, weight loss, frequent defecation, menstrual abnormalities, insomnia, headaches;
Objective - Impaired attention span and memory, hypervigilance, systolic flow murmurs, skin changes (warm, moist, smooth), EKG changes (sinus tachycardia, atrial fibrillation), psychiatric problems (depression, mania, bipolar disorder, manic psychosis), chorea, thyrotoxic penodic paralysis, thyroid storm, ocular features.

Neuropsychiatric signs include impaired attention, concentration, and memory, as well as emotional lability, nervousness, hypervigilance, lethargy, depression (i.e., apathetic hyperthyroidism), mania, psychosis, insomnia, and agitated delirium. Apathetic hyperthyroidism most frequently occurs in the elderly, lacks the usual hyperadrenergic features, and may easily be confused with depression or dementia.