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Gluten Encephalopathy with Psychiatric Onset

Gluten Encephalopathy with Psychiatric Onset

Gluten Encephalopathy with Psychiatric Onset

Woman thinking and solving a problemNicola Poloni, Simone Vender, Emilio Bolla, Paola Bortolaso, Chiara Costantini and Camilla CallegariDepartment of Clinical Medicine-Psychiatry, University of Insubria, Via O. Rossi 9, 21100 Varese, Italy Clinical Practice and Epidemiology in Mental Health 2009, 5:16doi:10.1186/1745-0179-5-16

The electronic version of this article is the complete one and can be found online at:

http://www.cpementalhealth.com/content/5/1/16
Received: 7 July 2008
Accepted: 26 June 2009
Published: 26 June 2009

- 2009 Poloni et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), Which permits unrestricted use, Distribution, and reproduction in any medium, Provided the original work is properly cited.

Abstract:

Many cases of coeliac disease, a gastrointestinal autoimmune disorder caused by sensitivity to gluten, can remain in a subclinical stage or undiagnosed. In a significant proportion of cases (10-15%) Gluten intolerance can be associated with central or peripheral nervous system and psychiatric disorders.

A 38-year-old man was admitted as to our department an inpatient for worsening anxiety symptoms and behavioral alterations. After the addition of second generation Anti-Psychotic to the therapeutic regimen, The patient presented neuromotor impairment with high fever, Sopor, Leukocytosis, Raised Rhabdomyolysis-Related indicators. Neuroleptic malignant syndrome was strongly suspected. After worsening of his Neuropsychiatric conditions, With the onset of a frontal cognitive deficit, Bradykinesia and difficulty walking, Dysphagia, Anorexia and Hypoferraemic Anaemia, SPET revealed a reduction of cerebral perfusion and ENeG results were compatible with a mainly motor polyneuropathy. Extensive laboratory investigations gave positive results for Anti-Gliadin antibodies, and an appropriate diet led to a progressiveremission of the encephalopathy.

Introduction:

Coeliac disease is an inflammatory disease of the upper small intestine resulting from gluten ingestion [1]. The diagnosis is based on: A clinical picture suggesting malabsorption of nutrients, Serology for Anti-Gliadin, Anti-Endomysial and Anti-Transglutaminase antibodies, Sometimes a biopsy of the intestinal mucosa, and resolution of the lesions following the institution of a Gluten-Free diet [1]. Many cases of coeliac disease long remain in a subclinical stage [2], Or undiagnosed because of poor awareness of the condition among primary care physicians [1]. In a significant proportion of cases (10-15%) Gluten intolerance can be associated with central or peripheral nervous system disorders, such as cerebellar ataxia, Myoclonus, Epilepsy, Ophthalmoplegia, Dementia, Multifocal Leukoencephalopathy, Peripheral Neuropathies and Myopathies [3] and with psychiatric disorders such as Anxiety, Depression, Psychotic Symptoms and personality disorders [4]. These manifestations are sometimes the presenting symptoms of the disease [4-6]. The Physiopathological mechanisms underlying these associations are still not known, Even though genetic causes [6] and autoimmune factors [7,8] have been Hypothesised.

The literature describes cases of cerebral perfusion abnormalities in untreated coeliac patients [9,10]. There is also a report of a case of regression of frontal hypoperfusion following the institution of a Gluten-Free diet [9].

Case Report:

In May 2001, a 38-year-old man with anxious-depressive symptoms was referred to us for psychiatric assessment. These symptoms, occurring sporadically for around two years, had worsened following a protracted absence from work (Due to a Disabling right Wrist Fracture). The patient had a history of surgical operations to correct kyphoscoliosis.

He was diagnosed with reactive depressive disorder in the context of personality disorder NOS (Not Otherwise Specified) and put on paroxetine 10 mg with benzodiazepines. Following the appearance of bizarre behaviors and heteroaggressiveness towards family members, Anti-Psychotic therapy (Haloperidol Decanoate 50 mg every four weeks) was added. In May 2002, Worsening anxiety symptoms and behavioral alterations that could not be managed at home culminated in the patients Hospitalization in our department for Re-Assessment and review of therapy. Two days after the addition of risperidone 2 mg to the existing therapeutic regimen (Citalopram 20 mg and BDZ) the patient presented muscle rigidity, Cramp-Like muscle pain and increased Osteo-Tendinous reflexes leading to bradykinesia and difficulty walking. Withdrawal of the Anti-Psychotic drug did not improve the picture significantly. Laboratory investigations revealed raised CK (536 U/l) and a brain CT-Scan showed an area of hypodensity of possible ischaemic origin in the posterior fossa, as well as moderate deepening of the cortical sulci in the Frontal-Temporal region bilaterally. EEG showed mild, Non-Specific, Non-Focal abnormalities.

The severe anxiety symptoms and behavioral alterations persisted and a week later Anti-Psychotic treatment was Re-Introduced. The clinical picture, already characterized by neuromotor impairment, Worsened abruptly and unexpectedly, With the onset of high fever (39C), Sopor, Acute respiratory insufficiency with peripheral cyanosis, Leukocytosis (WBC Count 16680/mm3), and raised Rhabdomyolysis-Related indicators (CK 1216 U/l and LDH 718 U/l). The patient was transferred to the infectious diseases department. Since neuroleptic malignant syndrome was strongly suspected, The Anti-Psychotic was withdrawn and dantrolene 50 mg/day and Cardio-Respiratory support were started, Substantially resolving the acute symptomatology. The patient developed an Enterococcus faecalis infection of the urinary tract and Deep-Vein thrombosis (DVT), Which were treated with antibiotic therapy and subcutaneous heparin.

Although the patients general conditions improved, The neurological picture of diffuse muscle rigidity, Psychomotor slowing and dysarthria persisted and despite further investigations (MRI, Evaluation of Autoantibodies and Circulating Immunocomplexes) Continued to lack a plausible explanation.

In mid-June, a further worsening of his neuropsychiatric conditions prompted his readmission to our department. During this second stay, he displayed the progressive onset of a frontal cognitive deficit together with affective lability, behavioural and affective regression, and verbal and motor stereotypes. Furthermore, the appearance of dysphagia and anorexia led to significant weight loss (20 kg in two months) which necessitated parenteral nutrition.

The patient was then sent to the Neuropathology Unit at the C. Besta Neurological Institute in Milan, Where single photon emission computed tomography (SPECT) revealed a reduction of perfusion and thus of neuronal activity and density in the right superior and middle frontal gyri, The left superior frontal gyrus, and the left medial temporal and occipital gyri; Electroneurography (ENeG) results were compatible with a mainly motor polyneuropathy. Subsequently, Mild hypoferraemic anemia was found. Gluten sensitivity tests (Part of Further and More Extensive Laboratory Investigations) Gave positive results for Anti-Gliadin (IgG 32 UI/ml), Anti-Endomysial and Anti-Transglutaminase Antibodies). A appropriate diet was instituted and led to a progressive remission of the encephalopathy and an improvement in the psychiatric symptoms and the lesions detected on SPECT and ENeG, Which, at follow up, Were no longer present. After a period of rehabilitation, This patient is still followed by our psychiatric service for mild anxiety symptoms. He takes olanzapine 2.5 mg and derives benefit from the treatment.

Conclusion:

The diagnostic process in this patient proved particularly complicated. This is, in fact, a case of clinical onset of coeliac disease in adulthood, Without signs of malabsorption and with exclusively psychiatric involvement (Non-Specific Anxious-Depressive symptoms associated with effective and behavioral personality disorders). In our view, This clinical picture could be attributed to the SPET-Documented frontal hypoperfusion. This would indeed explain the lack of benefit of the initial psychopharmacological treatment and the progressive worsening of the symptoms that, Together with the onset of behavioral disinhibition, Necessitated the patients hospitalization. During hospitalization, The administration of Anti-Psychotic drugs triggered the onset of neuroleptic malignant syndrome, Which, Initially atypical (Without Fever and Leukocytosis) and then full blown, Slowed down the diagnostic process and delayed the recognition of the true nature (Organic) of the etiology. We cannot rule out the possibility that this coeliac patient presented a particular susceptibility to this rare complication associated with the use of Second-Generation antipsychotic drugs [11], Given the cerebral involvement documented on brain CT-Scan and Subsequently on SPECT. The picture was complicated further by the onset of DVT and a urinary tract infection, Probably due to the patients prolonged confinement to bed.

After the resolution of the acute picture, There remained a progressively worsening Psycho-Organic Syndrome, Secondary to the Above-Mentioned cerebral involvement, and neuromotor deficits due to the polyneuropathy detected on ENeG. The case we describe recalls literature reports of an Adult-Onset progressive frontal, Subcortical-Type cognitive deficit, Characterized by confusion, Personality disturbances and associated neurological (Ataxia-and Peripheral Neuropathy-Type) pictures, Coinciding with the exacerbation of a malabsorption syndrome [12].

The appearance of the first signs pointing to malabsorption, i.e., The weight loss and hypoferraemic anaemia, Finally prompted us to investigate a possible autoimmune etiology, and to test for Anti-Gliadin antibodies, For which the patient was positive.

The diagnostic hypothesis of gluten encephalopathy was confirmed by the remission of the symptoms and of the lesions observed on SPECT following the institution of an appropriate diet.

In addition to the objective diagnostic difficulties presented by this case, We wish to add a further, Ideological Consideration, Relating to an unwitting tendency of colleagues from other specialist disciplines to stigmatise patients classified as Psychiatric. Indeed, Both the possible organic etiology of the clinical picture and the concomitant medical disorders presented by Psychiatric Patients are often underestimated, Slowing down the diagnostic process and the taking of the necessary therapeutic measures.

Consent:

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing Interests:

The authors declare that they have no competing interests.

Authors Contributions:

NP has made substantial contributions to the acquisition of clinical data; VS has given the final approval of the version to be published; BE has made substantial contributions to the acquisition of clinical data; PB participated in the analysis and interpretation of clinical data; CC was involved in drafting the manuscript; CC was involved in revising the manuscript critically.

All authors read and approved the final manuscript.

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References:

  1. Catassi C, Kryszak D, Louis-Jacques O, Duerksen DR, Hill I, Crowe SE, Brown AR, Procaccini NJ, Wonderly BA, Hartley P, Moreci J, Bennett N, Horvath K, Burk M, Fasano A: Detection of celiac disease in primary care: a multicenter case-finding study in North America.
    Am J Gastroenterol. 2007, 102(7):1454-1460.
  2. Wills AJ, Unsworth DJ: The neurology of gluten sensitivity: separating the wheat from the chaff.
    Curr Opin Neurol. 2002, 15(5):519-523.
  3. Wills AJ: The neurology and neuropathology of coeliac disease.
    Neuropathol Appl Neurobiol. 2000, 26(6):493-496.
  4. Martinez-Bermejo A, Polanco I: Neuropsychological changes in coeliac disease.
    Rev Neurol 2002, 34(Suppl 1):S24-33
  5. Hadjivassiliou M, Grunewald RA, Chattopadhyay AK, Davies-Jones GA, Gibson A, Jarratt JA, Kandler RH, Lobo A, Powell T, Smith CM: Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia.
    Lancet. 1998, 352(9140):1582-1585.
  6. Hadjivassiliou M, Grunewald R, Sharrack B, Sanders D, Lobo A, Williamson C, Woodroofe N, Wood N, Davies-Jones A: Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics.
    Brain. 2003, 126(Pt 3):685-691.
  7. Vaknin A, Eliakim R, Ackerman Z, Steiner I: Neurological abnormalities associated with celiac disease.
    J Neurol. 2004, 251(11):1393-1397.
  8. Hadjivassiliou M, Grunewald RA, Kandler RH, Chattopadhyay AK, Jarratt JA, Sanders DS, Sharrack B, Wharton SB, Davies-Jones GA: Neuropathy associated with gluten-sensitivity.
    J Neurol Neurosurg Psychiatry 2006, 77(11):1262-6.
  9. Usai P, Serra A, Marini B, Mariotti S, Satta L, Boi MF, Spanu A, Loi G, Piga M: Frontal cortical perfusion abnormalities related to gluten intake and associated autoimmune disease in adult coeliac disease: 99mTc-ECD brain SPECT study.
    Dig Liver Dis. 2004, 36(8):513-518
  10. Addolorato G, Di Giuda D, De Rossi G, Valenza V, Domenicali M, Caputo F, Gasbarrini A, Capristo E, Gasbarrini G: Regional cerebral hypoperfusion in patients with celiac disease.
    Am J Med. 2004, 116(5):312-317
  11. Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T: Neuroleptic malignant syndrome and atypical antipsychotic drugs.
    J Clin Psychiatry. 2004, 65(4):464-470
  12. Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA: Cognitive impairment and celiac disease.
    Arch Neurol 2006, 63(10):1440-6

Amniotic Tissue Cells for Joint Injection

Amniotic Tissue Cells for Joint Injection

Joint Health

For years patients with Arthritis, Repetitive Motion Injuries, Soft Tissue Injuries, Joint Health and other serious degenerative joint conditions have struggled with limited treatment options, Including:

  • Painful and Frequent Injections of Steroids and Cortisone
  • Costly Joint Replacement Surgery
  • Chronic Pain Management

Amniotic Tissue Therapy: Advanced Technology Combined with Traditional Holistic Methods

At (NAME OF PRACTICE), We combine new and advancing technology with safe, traditional, effective holistic medical practices to successfully treat soft tissue and degenerative joint conditions through the use amniotic tissue therapy.

Used in medical treatments for over 80 years, amniotic fluids have been found to protect and aid in growth of new cells and tissue. Using advanced medical technology, and using fluoroscopic or ultrasound guidance, our doctors now regularly inject amniotic tissue into damaged portions of joints or tissue to promote growth and repair of cells in their patients.

What Are Amniotic Tissue Cell Injections?

Using amniotic stem cells delivered through direct injection, the body immediately begins repairing, Joint Health, regrowing, and restoring damaged cells, tissue, joints, tendons and ligaments. In addition to the healing and restoring properties, amniotic tissue injections contain multi-potent cells that:

  • Reduce Inflammation and Pain through Natural Anti-Inflammatory Agents (Cytokines), Much like traditional steroid and cortisone injections
  • Restore Mobility, By lubricating joints and tendons with Hyaluronic Acid
  • Promote New Tissue Growth and Nutrition using high concentrations of proteins, lipids, carbohydrates, and growth hormones

Benefits of Amniotic Tissue Cell Therapy

In addition to being very safe and extremely effective, amniotic tissue cell therapy provides several specific benefits, including:

  • Steroid-Free, Natural Anti-Inflammatory Cells for advanced pain relief
  • Enhanced Lubrication from Hyaluronic Acid
  • Stimulation of New Tissue Growth
  • Safe Treatment with No Concern of Immune System Rejection by the patient
  • A Highly Concentrated Source of Stem Cells (Unlike injections of embryonic cells or cells harvested from the patients own bone marrow)

How Does Amniotic Tissue Cell Therapy Work?

Using cells gathered from the amniotic sac, amniotic tissue cell therapy provides immune privileged, multi-potent stem cells to the damaged area. Unlike cells from other tissue in the body, amniotic stem cells injections will not be rejected or cause an immune system reaction. In addition to being immune privileged, amniotic tissue:

  • Contains Collagen Matrices (Protein frameworks for new cells and tissue to grow around)
  • Is Multipotent, Meaning it can grow as any type of body cell (Including Muscle, Cartilage, Organ, etc)
  • Uses the bodys ability to heal itself to Restore Degenerated Tissue, Replace Damaged Cells, and Promote Growth of New Tissue

Common Conditions Treated with Amniotic Tissue Therapy:

  • Osteoarthritis
  • Bone-on-Bone Joints
  • Soft Tissue Injuries
  • Degenerative Joint Diseases
  • Repetitive Motion Injuries (i.e. Carpal Tunnel, Rotator Cuff)
  • Chronic Tendonitis and other Tendinopathies
  • Ligament Damage
  • Other Inflammatory Diseases

Are Amniotic Tissue Injections Safe?

Yes. Consider the following:

  • To date, over 10,000 amniotic tissue cell injections have been administered without one reported adverse or unwanted side effect
  • Amniotictissue cells are immunoprivileged; rejection by the body is extremely rare
  • Amniotic tissue therapy has been used for decades, is effective, safe, and has undergone rigorous research and screening processes by the FDA

Am I a Candidate for Amniotic Tissue Therapy?

Anyone suffering from any form of pain in the joints, ligaments, or tendons may be a candidate for amniotic tissue therapy. In rare cases, patients suffering from severe or advanced forms of degenerative joint disease or arthritis may not qualify for this therapy. After evaluation, Dr. Stephen Smith will provide patients with recommendations for alternative treatment for Joint Health.

Note: Amniotic stem cells come from the amniotic sac, not an embryo. While there have been ethical concerns surrounding the use of embryonic stem cells, most medical professionals agree that amniotic tissue therapy is effective and raises no ethical concerns.

10 Organic Foods You Should Buy

10 Organic Foods You Should Buy

Organic Foods

Apples              organic apples

Conventionally grown apples contain the highest traces of pesticides in supermarkets than any other crop. Even after apples were washed, 48 types of pesticides were discovered by the EWG. Farmers use a wide range of chemicals on apple crops because they're highly susceptible to regional insect infestation and blights. Apple skins absorb these pesticides to fight these environmental problems, but the chemicals remain in the fruit long after harvest. In addition to organic foods apples not being laden with as many pesticides, their skins have been shown to contain 15 percent more antioxidants than non-organic apples.

Celery             

Celery has no protective skin, so it is vulnerable to contact with insecticides and pesticides. Celery stocks are also porous, so they retain the pesticides that theyre treated with, which can be up to 13 different types.

Cherry Tomatoes

In the EWG study, a single sample of cherry tomatoes tested positive for 13 different pesticides. Because of the way they grow in dense clusters, theres more surface area to spray, which results in more chemical product on the fruit. Their thin skins make it easy for chemicals to leach into the flesh of the fruit.

Organic Foods

Cucumbers

Non-organic cucumbers were found to contain 69 types of pesticides in the 2013 EWG study. If you cant find organic, peel the cucumbers because the waxes on the skin that make them shiny also tend to hold onto chemical treatments.

Grapes      

Grapes ripen quickly, so theyre more prone to mold and insects. As a result, grapes are heavily sprayed. The U.S. Department of Agriculture Pesticide Data Program found grape crops contained 34 pesticide residues, four of which are known to be or are probably carcinogenic. When tested, imported Chilean grapes contained 17 various chemicals.

Peaches     

In the weeks before harvest, conventional farmers spray peaches with pesticides to guarantee perfect-looking fruits on the shelves. Even if you wash and peel a non-organic peach before eating it, it would be impossible to get rid of all 62 pesticides found by the USDA.

Organic Foods

Potatoes

Even root vegetables that grow underground are susceptible to chemical treatment. Potato vines grow above the surface, and farmers regularly spray them with pesticides when conventionally grown. Farmers also treat the soil with fungicide to further prevent diseases like potato blight. For this reason, the average potato contains a higher total weight of pesticides than any other edible crop.

Spinach         

Farmers spray non-organic salad greens, especially spinach and lettuce, with potent pesticides right onto their leaves. Organic farmers combat the insects and worms that like to snack on them by using traps, non-toxic repellents, and mesh nets to keep natural attackers at bay.

Organic Foods

Strawberries     

Strawberries are a delicate fruit with thin skin thats prone to growing fungus. To combat this, conventional farmers spray them with pesticides that linger even after they hit the produce section. The nooks and crannies in strawberries also make contain a higher concentration of pesticide compound. Experts have detected almost 60 different types of pesticides in washed strawberries.

Peppers         

Peppers, especially sweet bell peppers, are highly susceptible to insect infestation, so when they're grown non-organically, they're generously sprayed with insecticides. Their thin crunchy skins absorb pesticides like a sponge. Testing showed 50 different pesticides on sweet bell peppers. Try to stick to organic peppers.

ARTICLE SOURCE: We have not modified the factual content from this source on buying organic food. This content is syndicated news that can be used for your research, and we hope that it can help your productivity. This content is strictly for educational purposes and is not made for any kind of commercial purposes of this blog.

Can Fibromyalgia Syndrome Be Treated?

Can Fibromyalgia Syndrome Be Treated?

Fibromyalgia Syndrome

Fibromyalgia Syndrome (FMS) is a chronic, painful, and sometimes disabling condition commonly encountered by primary care physicians. Recent research has provided information about the pathophysiology of FMS that has implications for treatment. For example, it now seems most likely that the major pathophysiologic mechanisms of FMS involve central sensitization in the CNS, although a peripheral source of nociception may initiate and/or perpetuate this sensitization.

Thus, drugs that act through the CNS (such as tricyclic agents, selective serotonin reuptake inhibitors [SSRIs], and tramadol) are more likely to be effective than those that act primarily at a peripheral level-for example, NSAIDs. The same CNS mechanism may also explain why hypnotherapy or meditation may be beneficial in Fibromyalgia syndrome.

Understanding pathophysiologic mechanisms, as discussed in our article in the September 1, 2003, issue 1, is important for treating disease. Although the mechanisms in Fibromyalgia syndrome are incompletely understood at this time, the relevant factors for treatment purposes include central sensitization (Amplified or Perpetuated by Poor Sleep); Psychological Distress; Peripheral Pain Generators (eg, Overuse of Body Parts, Repetitive Trauma, and Arthritis); Deconditioning; and other aggravating factors (eg, Weather, Noise, and Comorbid Conditions).

The management of Fibromyalgia syndrome has been reviewed in detail. Key components of treatment are shown in Table 1. [See the original article.] We will describe each of these below.

Positive and Empathetic Attitude of the Physician:

The management of Fibromyalgia syndrome begins with the very first contact with the patient. Many patients with aches and pains have had an unhelpful or even unpleasant experience with their previous health care providers, or heard of such experiences from their friends. Greeting a patient in a friendly and positive manner goes a long way to assure that you are a kind and interested physician. Maintain such an attitude of caring throughout the period of consultation and subsequent follow-ups.

Making a Firm Diagnosis:

As we emphasized in our previous article, Fibromyalgia syndrome should be diagnosed by its own characteristic features of widespread pain and multiple tender points, and not by Ruling out other conditions, as stated in the American College of Rheumatology (ACR) criteria. Ordering one more test to exclude such and such disease may cause anxiety, since such an approach is not only unnecessary, it may also indicate uncertainty on the part of the physician, and thus erode a patients confidence in him or her.

Patient Education, Reassurance, and Individualization of Treatment:

After the diagnosis is made, patient education is a most important step. Provide information to patients with Fibromyalgia syndrome, in a simple, understandable way regarding the diagnosis and probable cause, aggravating factors (Table 2), and prognosis, and then use Table 1 to discuss various elements of management. Emphasize that a patients pain and other symptoms are Real and based on a Chemical Imbalance, Such as excessive substance P and decreased serotonin.

However, reassure your patient that Fibromyalgia syndrome is not life-threatening (despite much pain), and that it does not cause tissue damage. (We avoid using the term Benign Because patients who are suffering may resent it.) Advise on general healthy behavior, including weight loss, smoking cessation, good sleep habits, and regular exercise. Also emphasize the need for both nonpharmacologic and pharmacologic therapy. A recent study has found an association between overweight and several important FMS features, such as fatigue, decreased physical function, and increased number of tender points. Smoking is positively associated with pain, global severity, and functional difficulties.

Tailor your management according to each patients symptom profile. For example, some patients may have significant psychological distress, while others have a predominant sleep problem, and yet others have specific aggravating factors, such as poor sleep, repetitive trauma (vocational and recreational), and mental stress. Some patients cope with their symptoms fairly well, while others do not. Although Fibromyalgia syndrome is a chronic painful condition, emphasize that most patients find relief with appropriate treatment for a period of time, and that during this time they can be meaningfully functional.

Addressing Aggravating Factors:

Aggravating factors that should be addressed are listed in Table 2. The importance of physical fitness (in the context of deconditioning) will be described in detail under Nonpharmacologic Intervention. Other important factors will be discussed here. Note that treatment of concomitant hypothyroidism does not eliminate Fibromyalgia syndrome symptoms, but it may help relieve fatigue and low energy.

Psychological Factors: Psychological distress is correlated with pain, including pain in FMS. Thus, psychological factors, such as anxiety, stress, depression, and poor coping, should always be addressed. Stress is an important factor in both triggering and perpetuating Fibromyalgia syndrome symptoms. Besides counseling for psychological difficulties, anxiolytics and antidepressants in appropriate doses may be required. SSRIs are as effective as tricyclic agents for depression and have fewer side effects. If necessary, refer patients to a psychologist for stress reduction or to a psychiatrist for refractory anxiety and depression.

Improving Sleep Quality: Nonrestorative sleep exacerbates pain and fatigue. Poor sleep at night predicts pain the next day. Take a good sleep history and offer suggestions for improved sleep quality (Table 3). Morning fatigue is a sensitive indicator of nonrestorative sleep. Restless legs syndrome and/or periodic limb movement disorder is an important cause of sleep disturbance and is treatable with medications (see Pharmacologic Management).

Environmental Factors: Depending on individual sensitivity to specific weather factors, advise your patients to avoid unnecessary outside trips in the winter and to stay in comfortable temperature in an air-conditioned room in the summer as much as possible. Many patients are also sensitive to noise, smell, and light. Hyperresponsiveness to many of these environmental stimuli, as well as to many medications, is thought to be attributable to central sensitization.

Occupational Factors: Prolonged sitting or standing at work, adverse ergonomic factors that cause muscle or other soft tissue strain, repetitive motion, and job stress and dissatisfaction may all contribute to Fibromyalgia syndrome symptoms. Based on current knowledge of pain physiology, repetitive motions are likely to cause central sensitization and subsequent amplification and intensification of pain. Because an important goal of treatment of FMS is to keep the patient employed, both for psychological and economic reasons, these work-related aggravating factors should be discussed with the employer, along with appropriate recommendations, such as change of duties and improvement of adverse ergonomic conditions.

Comorbid Conditions: Although this theory has not been directly proved in patients with Fibromyalgia syndrome, current knowledge of central sensitization operative in Fibromyalgia syndrome suggests that any continued source of peripheral nociception enhances this sensitization and worsens pain. Thus, arthritis of any kind, neuropathy, or headaches should be treated. Restless legs syndrome disturbs sleep (Table 2).

Family and Social Factors: Adverse family circumstances, such as a stressful marriage, demanding children, and a lack of empathy and understanding by family members, can add significant distress. This, in turn, may aggravate pain, fatigue, and other associated symptoms, such as headaches and migraine. However, excessive attention from a solicitous spouse may also adversely affect a patients pain. Refer your patient to a psychologist for assistance with coping skills, if needed. Encourage patients to have a hobby and a network of support.

Nonpharmacologic Approach:

When primary care physicians inquire about Fibromyalgia syndrome treatment, they commonly ask,I have used such and such medications without success. What should I try next? This is unfortunate, since nonpharmacologic approaches, including patient support and education (Table 1), are an essential component of Fibromyalgia syndrome therapy and should be used in parallel with drug treatment with equal emphasis. Often physicians do not optimally utilize nonpharmacologic therapies. Patients who use both nonpharmacologic and pharmacologic therapies have better results than with either modality alone.

Physical Fitness: Many patients with FMS are deconditioned. Several controlled studies have shown the benefits of regular exercise in ameliorating Fibromyalgia syndrome symptoms, including pain. However, randomized, controlled studies that did not preselect patients based on their ability to engage in exercises did not demonstrate such benefit. I think the reason is obvious: it is difficult for most Fibromyalgia syndrome patients to exercise vigorously enough to achieve cardiovascular fitness.

But some exercise is better than none for overall health benefit, and it is important to be persistent in encouraging and monitoring a patients exercise at every office visit. We emphasize that in the phrase Regular Exercise, Regular is more important than exercise. It is the habit of initiating an exercise every day that is crucial.

We insist that patients keep a daily diary of their physical activities, preferably in graphic form (how much time spent and the peak pulse rate) and bring the weekly graphs for our inspection during the next visit. We encourage our patients by saying that everyone can exercise. The key is to start slowly - for example, only 2 to 3 minutes of exercise a day, if need be.

Ask patients to gradually increase the exercise time, say by 2 to 3 minutes each week, to the ideal 20 to 30 minutes of brisk exercise every day. Treadmill or outdoor walking, aerobic dancing, and swimming are excellent forms of exercise, depending on patient preference. Muscle strengthening exercises, started gradually as above, is useful in reducing the effort needed to do a given task, and is likely to lessen fatigue.

Physical Therapy: No controlled data exist to show that physical therapy by itself helps patients with Fibromyalgia syndrome. However, clinical observation suggests that a subgroup of patients report significant benefit from such therapy for a few days. Physical therapy modalities include local heat (moist or dry), ultrasound, stretching, range of motion exercises, muscle strengthening exercises, manipulation, and correction of posture. After initial demonstration by a therapist, many of these modalities may be used by a patient at home regularly.

Electromyographic Biofeedback: Current data on the efficacy of electromyographic (EMG) biofeedback alone are contradictory. However, if facilities are available, this modality may be prescribed along with other important forms of therapy, such as education, exercise, and medication. Some patients may benefit if they can be persuaded to try EMG biofeedback for at least 4 months or longer.

Acupuncture and Transcutaneous Electrical Nerve Stimulation (TENS): One double-blind controlled study has shown the benefit of electroacupuncture in Fibromyalgia syndrome over 3-week period. Long-term studies is needed. Appropriate studies showing the efficacy of conventional acupuncture or TENS are lacking. Some patients report benefit, but others report aggravation of pain from acupuncture or TENS therapy.

Cognitive behavioral therapy and multidisciplinary treatment: Cognitive behavioral therapy(CBT) involves training patients in coping skills, healthy behavior patterns, and restructuring of maladaptive beliefs, such as catastrophizing (I have a serious disease like cancer, and I may die of it) or significant pessimism (My symptoms are killing me and I will never get better. I cannot do exercise; I cannot do anything).

Although a few nonrandomized studies using waiting list controls demonstrated the benefit of CBT in Fibromyalgia syndrome, two well-designed randomized investigations using attention controls (who received adequate patient education regarding Fibromyalgia syndrome and its management, but without structured comprehensive CBT) demonstrated no benefit in the group that used CBT (Which is Time-Consuming and Expensive) compared with the control group.

We have found that some - but not all - Difficult Fibromyalgia syndrome patients (those who did not respond to usual treatment) whom we referred to a competent psychologist for CBT derived some benefit. However, one may argue that CBT should be started early (particularly in those showing poor coping skills during the initial consultation) rather than late, before maladaptive behaviors become ingrained.

Instead of recommending multidisciplinary treatment in a group setting under one umbrella, we individualize care and refer patients to an appropriate facility (Physical Therapy, Exercise, CBT, etc) as needed. Multidisciplinary treatment is expensive and often not covered by insurance and, because of the group setting, does not focus on an individual patients concerns. Its value is yet to be determined by randomized, double-blind controlled studies.

Hypnotherapy: One controlled study has shown the benefit of hypnotherapy in Refractory Fibromyalgia syndrome. we believe hypnotherapy is worth trying in an otherwise nonresponsive patient if a competent therapist is available.

Meditation: In an open but otherwise well-designed study, weekly supervised meditation for 10 weeks was impressively beneficial in more than half of patients. Patients were also required to meditate daily for 50 minutes at home. In practice, however, patients may not be willing to comply with such a time-consuming regimen.

Pharmacologic Treatment:

Drug treatment is as important as nonpharmacologic therapy. Randomized, double-blind, controlled studies have shown the efficacy of several drugs in FMS; however, long-term data are not available. Because evidence-based medicine is appropriately emphasized in current medical practice, agents with clinically demonstrated efficacy should be tried first.

We then use other drugs in the same class (e.g., Tricyclic agents other than amitriptyline) that have a similar mode of action, despite the fact that these drugs may not have been studied in controlled trials. Like any treatment modality, Drug therapy needs to be individualized, Depending on symptom severity, Comorbid psychiatric or Organic Diseases, Sleep Difficulties, and history of side effects. Drug treatment in Fibromyalgia syndrome has been reviewed.

Simple Analgesics: Simple analgesics, such as acetaminophen, may be prescribed for patients with mild or mild to moderate pain. NSAIDs were ineffective in several studies of patients with FMS. However, these agents may be used for concomitant conditions, Such as arthritis and dysmenorrhea, with the usual precautions.

Table 4 lists the centrally acting drugs that have been found useful or effective in Fibromyalgia syndrome, including those that were studied in controlled trials. Their dosages and common side effects are also listed.

Tricyclic Agents: These drugs are reuptake blockers of both serotonin and norepinephrine, neurotransmitters that are implicated in the inhibitory pathway of pain physiology. Amitriptyline 2,16 and cyclobenzaprine 2,17 are the most widely used, based on their demonstrated efficacy in several studies. A lower dose of amitriptyline than that used in depression is effective in Fibromyalgia syndrome. The usual dose is 25 to 50 mg at bedtime. In patients who have side effects at 25 mg, start with a lower dose, i.e., 10 mg, and gradually titrate to 50 to 75 mg at bedtime.

Common adverse reactions include grogginess, dry mouth, daytime sleepiness, weight gain, and paradoxical insomnia. Cardiac arrhythmias, mostly associated with tricyclic antidepressants, occur rarely; use caution in prescribing these agents in patients with heart disease and in elderly persons. Cyclobenzaprine, a drug related to the tricyclics but without antidepressant properties, is as effective as amitriptyline and has similar side effects. The Long-Term efficacy of tricyclic agents in Fibromyalgia syndrome is not known.

SSRIs: Fluoxetine alone at an average dose of 55 mg/d was effective in most outcome measures in a double-blind, randomized, controlled study of women with Fibromyalgia syndrome. A similarly controlled study of a combination of fluoxetine, 20 mg in the morning, and amitriptyline, 10 to 25 mg at bedtime, found that this combination was significantly more effective than either drug alone in relieving both pain and poor sleep. Studies have shown that a drug with both serotonergic and noradrenergic properties works better in chronic pain.

Remember, the dose of a tricyclic drug, when used in combination with an SSRI (particularly fluoxetine), should be kept low to avoid serious drug interactions resulting in tricyclic overdose; blood tricyclic level should be checked if such an interaction is suspected. Other SSRIs shown in Table 4 have not been studied in Fibromyalgia syndrome, but anecdotal observation supports their benefit, particularly in combination with a low-dose tricyclic agent (10 to 50 mg at bedtime).

Other antidepressant medications. Many patients in our clinic have reported benefit from venlafaxine, trazodone, andnefazodone, but controlled studies are lacking.

Other Centrally Acting Drugs:

Tramadol, like cyclobenzaprine, is a centrally acting drug without antidepressant properties. It is a reuptake inhibitor of serotonin and norepinephrine, but it also binds weakly with -opioid receptors. Although reports of addiction are rare, tramadol should not be prescribed in patients with a history of drug (including alcohol) abuse. Tramadol was effective in a randomized, double-blind controlled trial of patients with Fibromyalgia syndrome. In our practice, we prescribe 400 to 800 mg/d in divided doses with food. Smaller doses should be tried first and increased to the optimal dose, because adverse reactions (Such as GI Effects, Dizziness, and Somnolence) are common.

Note that drugs with demonstrated efficacy in randomized, double-blind studies are not all antidepressants, which suggests that depression is not synonymous with Fibromyalgia syndrome. Moreover, tricyclic antidepressants have a direct central analgesic effect in Fibromyalgia syndrome irrespective of their effect on depression.

Medications for associated symptoms. Hypnotic agents are useful for induction of sleep, but not for sleep maintenance or pain. Tricyclic agents are a better choice for restorative sleep in patients with Fibromyalgia syndrome. Associated significant anxiety and depression should be adequately treated with anxiolytic agents (such as alprazolam) and antidepressants; remember that a larger dose of antidepressants is required than the low dose prescribed for Fibromyalgia syndrome symptoms alone. For restless legs syndrome, there are several choices (all taken at bedtime):

Clonazepam, 0.5 to 2 mg.
Carbidopa-Levodopa, 25 to 100 mg, 1 or 2 tablets on an empty stomach.
Opioids (eg, Codeine (, 30 to 60 mg).Caveats include an increase in restless legs syndrome in the afternoon associated with Carbidopa-Levodopa and the potential abuse of codeine.

Tender Point Injections:

In an open study, injections of tender point sites were useful, with a median relief period of 3 months. We ask our patients to localize their most symptomatic sites with their own fingertips first and then we confirm those sites by palpation for injection. We use a 27-gauge 1-inch long needle and 1% or 2% lidocaine, 0.25 to 0.50 mL, usually in no more than 4 or 5 (Typically 2 to 4) sites. Make sure that the needle does not penetrate tissues beyond the muscles, to avoid such complications as pneumothorax.

Studies of myofascial syndrome suggest that the addition of corticosteroids has no advantage over lidocaine alone. Even dry needling is useful, although it is more painful than injection of a local anesthetic. Such injections may work by stimulating the local pain inhibitory neurons, probably Desensitizing the state of central sensitization in FMS, which may explain why the benefit lasts beyond the local anesthetic effects. Remember, the success of a tender point injection depends not only on the injection itself, but also Physician Effect (Positive Attitude, Support, Encouragement).

What About Narcotics?

Whether narcotics may be used in benign pain conditions such as FMS or osteoarthritis (OA) is a contentious issue among physicians. A double-blind, randomized controlled study of oxycodone (10 to 20 mg every 12 hours) in OA demonstrated its efficacy and relative safety over a period of 12 months.

We use narcotics quite uncommonly, and only when other management components have failed. We have found oxycodone, 10 to 30 mg/d in divided doses every 12 hours, and acetaminophen, 300 mg, with codeine, 30 mg, 2 to 4 times a day, beneficial. We use opioids mostly during a Flare-up, but they may be continued long-term provided no side effects or abuse emerges.

Although, theoretically, short-acting opioids may have a greater potential to induce addiction, we have not encountered such a problem in our practice. The key is to select patients carefully. A history of addiction or alcohol or drug abuse is a contraindication, and patients must be monitored regularly for Drug-Seeking behavior. Another caveat based on recent studies is that opioids can paradoxically increase sensitivity to pain in some persons. A patient who seems to need higher doses after some time may benefit from a decreased dose.

Complementary and Alternative Medicine:

Complementary and alternative medicine (CAM) in FMS has been reviewed. It remains, for the most part, unproved in Fibromyalgia syndrome. A large number of studies on St Johns wort have yielded contradictory results. This herb product cannot be confidently recommended at this time because of a lack of standardization in various manufacturers products; its potential serious interactions with other antidepressants, particularly SSRIs; and its ineffectiveness in severe depression.

S-adenosylmethionine (SAM-e) is a naturally occurring compound that, at a dose of 400 mg bid, Significantly improved pain, fatigue, and mood in a randomized, double-blind controlled study involving 44 Fibromyalgia syndrome patients. GI symptoms are the most common side effects, and an interaction with other antidepressants may occur. We have found SAM-e beneficial in a few of our patients.

Static magnetic therapy also relieved pain over a period of 6 months in a randomized, Double-Blind controlled study. We have not used this therapy so far, but it is worth trying in consultation with an expert in this area.

There are limited studies on CAM in Fibromyalgia syndrome, but for general information, the review by Crofford and Appleton is useful.

The figure shows a general pyramidal approach to Fibromyalgia syndrome management. Note that tender point injections may be used at any stage of treatment and opioid therapy is kept at the top rung of the pyramid.

Prognosis:

Although follow-up studies of patients with Fibromyalgia syndrome show no significant fluctuations over a period of several years, these studies have not evaluated symptoms frequently, for example, every 1 to 2 weeks. Our observations suggest that most patients experience significant relief with therapeutic interventions over a period of 2 to 12 weeks (sometimes longer), during which time they are also meaningfully functional. In a minority of patients, such relief may be sustained long-term. Thus, appropriate management is important.

Clinical Highlights:

? Reassure patients that fibromyalgia syndrome (FMS) is not life-threatening and will not cause tissue damage, and that their symptoms are real and likely caused by a chemical imbalance. Educate patients about such healthy behaviors as weight loss, smoking cessation, and good sleep habits.
? Stress may trigger or perpetuate Fibromyalgia syndrome symptoms, including pain. Besides counseling, pharmacologic agents such as antidepressants may be required. For patients who are anxious, anxiolytics at bedtime may be useful.
?Regular exercise is an important component of therapy. Have patients start gradually, if necessary, and encourage them to keep an exercise diary. Appropriate forms of exercise include walking, aerobic dancing, swimming, and muscle strengthening. Other nonpharmacologic modalities include physical therapy, electromyographic biofeedback, electroacupuncture, transcutaneous electrical nerve stimulation, cognitive behavioral therapy, hypnotherapy, and meditation.

?Simple analgesics, such as acetaminophen, may be prescribed for mild to moderate pain. NSAIDs are ineffective for FMS symptoms but may be helpful for concomitant conditions.

? Amitriptyline is an effective tricyclic antidepressant and the agent most extensively studied for Fibromyalgia syndrome. It is used in lower doses than those recommended for depression. Cyclobenzaprine has similar efficacy and side effects. Fluoxetine is effective alone at a higher dose and in combination with amitriptyline.

?Tender point injections generally relieve symptoms for 1 to 3 months. Ask the patient to localize the most symptomatic sites with his or her fingertips first, and then confirm those sites by palpation for injection. Use a 27-gauge 1-inch needle and 1% or 2% lidocaine, 0.25 to 0.50 mL, in no more than 5 (usually 2 to 4) sites.

ARTICLE SOURCE: We have not modified the factual content by Muhammad B. Yunus, MD and Sule Arslan, MD, on fibromyalgia from the source, Rheumatology Network.com. This content is for your research, and we hope that it can help. This content is strictly for educational purposes and is not made for any kind of commercial purposes of this blog.

Smokers Have Increased Risk of Breast Cancer

Smokers Have Increased Risk of Breast Cancer

Breast Cancer

NEW YORK (Reuters Health) - Current smokers and former heavy smokers have a greater risk of Breast Cancer (BC) recurrence and mortality than women who have never smoked, according to a new study.

For the report, Presented February 20 at the annual meeting of the Americasmoking health concernsn College of Preventive Medicine in New Orleans, Louisiana, Researchers reviewed records from 9975 Breast cancer survivors who were part of the After (BC) Pooling Project. Delayed entry Cox proportional hazard models were used to examine the relationship between breast cancer prognosis and a womans smoking status, Cigarettes per day, Years of smoking, and Pack-Years.

Former smokers with 20 to 35 Pack-Years of exposure had a 22 percent increased risk of breast cancer recurrence and a 26 percent increased risk of all-cause mortality compared to non-smokers. Those with 35 Pack-Years of exposure or more had a 37 percent increased risk of (BC) recurrence, a 54 percent increased risk of breast cancer mortality, and a 68 percent increased risk of all-cause mortality.

Current smokers (With a mean 39 Pack-Years of exposure) had a 41 percent higher probability of breast cancer recurrence, a 60 percent higher probability of breast cancer mortality, and double the risk of all-cause mortality compared to non-smokers. Former smokers with less than 20 pack-years of exposure had no increased risk of any outcome.

The findings were also published online December 7 in the Journal of the National Cancer Institute.

The authors believe this is the first study to discover a statistically significant, Dose-Dependent association between lifetime cigarette smoking and cancer recurrence and all-cause mortality. According to Co-Author Dr. Carolyn Senger from the University of California-San Diego in La Jolla, These findings are especially significant given that most longitudinal studies have indicated that breast cancer survivors who smoke have increased risk of all-cause mortality while women who quit after diagnosis do not.

Dr. Senger added, While the latest Surgeon General report and many studies have documented the way smoking affects cardiovascular and respiratory health, Which likely explains some of the impacts of smoking on mortality seen in most studies of cancer survivors, this new data suggests a Breast Cancer-Specific mechanism of risk.

She told Reuters in an email that the results emphasize the public health importance of early cessation to reduce long-term risk. While it surprised me that the increased risk was confined to heavy smokers, For practitioners seeing breast cancer survivors, There is an important opportunity to motivate women to quit smoking before they accumulate 20 Pack-Years of exposure, Dr. Senger said.

Dr. Laura Esserman, Director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco, agreed. We now have data that smoking impacts breast cancer mortality. Not that we need another reason to get people to stop smoking, But here is yet another important finding that cigarette smoking leads to health problems, She told Reuters Health. Any newly-diagnosed breast cancer patient who smokes should be put into a program to help them quit. If it is worth treating their breast cancer, it is worth helping them quit smoking.

ARTICLE SOURCE: We have not modified the factual content from the source. This content is syndicated news that can be used for your research, and we hope that it can help your productivity. This content is strictly for educational purposes and is not made for any kind of commercial purposes of this blog.

Making a Firm Diagnosis of Fibromyalgia and Understanding Its Pathophysiology

Making a Firm Diagnosis of Fibromyalgia and Understanding Its Pathophysiology

Diagnosis of Fibromyalgia

Chronic musculoskeletal aches and pains, as well as multiple tender points on palpation by an examiner, characterize fibromyalgia syndrome (FMS) in Diagnosis of Fibromyalgia. Its more common in women than men; about 90 percent of patients are women. The most common age of presentation is between 30 and 60 years. However, FMS has been well described among juveniles. FMS is a common condition. Its encountered among 2.1 percent, 5 percent, and 10 to 20 percent of patients seen in a family practice, internal medicine clinic, and rheumatic disease clinic, respectively. Scientists found the prevalence of FMS in a community at between 2 percent in Wichita, Kansas, and 3.3 percent in London, Ontario, Canada.Making a Firm Diagnosis of Fibromyalgia and Understanding Its Pathophysiology

The prevalence increases with age until 65 to 79 years. More than 7 percent of women had FMS in the 55 to 64 age group in a Canadian study and in the 60 to 79 age group in a U.S. study. The term Primary Fibromyalgia is used when a significant underlying or concomitant condition that may contribute to pain is absent in Diagnosis of Fibromyalgia. FMS may be classified as Concomitant When another condition, Such as rheumatoid arthritis (RA), Osteoarthritis, or Hypothyroidism is present and may contribute to pain or fatigue of FMS. However, currently the term FMS, or Fibromyalgia, Collectively applies to both primary and concomitant types. We describe clinical features, Diagnosis, and Pathophysiology in this article.

Clinical Features:

Symptoms. Besides widespread pain, Patients complain of many other symptoms, Such as Fatigue, Poor Sleep, a subjective swelling of soft tissues (and sometimes of the joints), Paresthesia (Sensation of tingling, Tickling, Prickling, Pricking, or Burning of a person's skin), Cognitive dysfunction, and symptoms of other associated conditions, Such as irritable bowel syndrome (IBS), Headaches, Restless legs syndrome, and Temporomandibular dysfunction. There is no significant correlation between subjective swelling or subjective numbness and psychological status.

Common sites of pain or stiffness are Low Back, Neck, Shoulder region, Arms, Hands, Knees, Hips, Thighs, Legs, and feet. Chest pain is not uncommon and tender points in the chest wall (also see differential diagnosis) accompany it. Fatigue is common in Diagnosis of Fibromyalgia and may be the presenting feature in some cases because of its severity. Several factors may contribute to, or Aggravate, Fatigue and pain in FMS, Such as nonrestorative sleep, Deconditioning, Overwork, Psychological factors, and poor coping skills. Patients are also sensitive to environmental stimuli, Such as noise.

Signs. Patients with FMS look healthy, but often they seem fatigued and in pain. Examination of the joints shows no objective swelling (Unless there is concomitant arthritis), But some patients have marked joint tenderness on palpation. Despite neurologic symptoms, Such as weakness and numbness, Neurologic examination in FMS is normal in Diagnosis of Fibromyalgia.

The most significant physical finding in FMS is the presence of multiple tender points in a widespread distribution. For the purpose of Diagnosis of Fibromyalgia, one needs to examine 18 specified sites (See Below), By application of a force of approximately 4 kg (Roughly the pressure one needs to whiten the nail bed when pressing against a firm surface), Using the index finger or the thumb. Note that practitioners must learn the proper way to examine a tender point, as in the case of examining other physical signs in medicine, Such as Hepatomegaly or Splenomegaly. An underestimation of the number of tender points in a patient with FMS is the most important reason for missing a diagnosis of this disorder.

Diagnosis of Fibromyalgia:

The American College of Rheumatology 1990 Criteria for the Classification of FMS:

1. History of widespread pain (for at least three months)
Definition: Pain is considered widespread when all of the following are present: Pain in the left side of the body, Pain in the right side of the body, Pain above the waist, Pain below the waist. In addition, Axial skeletal pain (Cervical spine or anterior chest or thoracic spine or low back) Must be present. In this definition, Shoulder and buttock pain are considered as pain for each involved side. Low Back Pain is considered lower segment pain. Thus, pain at three widespread sites (For example, Right arm, Low back, and Left leg) Will satisfy the criterion of widespread pain.

2. Pain in 11+ of 18 Tender point sites on digital palpation with an approximate force of 4 kg
Definition: Pain (Mild or Greater) on digital palpation must be present in at least 11 of the following 18 tender point sites:
Occiput: Bilateral, at the Suboccipital muscle insertions.
Low cervical: Bilateral, at the anterior aspects of the Intertransverse spaces at C5-7.Trapezius: Bilateral, at the midpoint of the upper border.
Supraspinatus: Bilateral, at origins above the scapula spine near the medial border.
Second rib: Bilateral, at the second Costochondral junctions, Just lateral to the junctions on upper surfaces.
Lateral epicondyle: Bilateral, 2 cm distal to the Epicondyles.
Gluteal: Bilateral, in upper outer quadrants of buttocks in anterior fold of muscle. Greater trochanter: Bilateral, Posterior to the trochanteric prominence.
Knee: Bilateral, at the medial fat pad proximal to the joint line.

For classification purposes, Patients will be said to have FMS if both criteria (1 and 2) are satisfied. The presence of a second clinical disorder does not exclude the Diagnosis of Fibromyalgia.
From Wolfe F et al. Arthritis Rheum. 1990

Laboratory Investigations:

It may surprise many physicians to learn that a diagnosis of FMS does not require any specific laboratory testing, Since Ruling out Does not apply to FMS. Practitioners should request laboratory tests, Including radiology, Only if they suspect another concomitant condition by careful history taking and physical examination. There's no reason to order tests of antinuclear antibodies or rheumatoid factor unless clinically indicated. However, a complete blood count and a chemistry panel with blood urea (Nitrogen, Creatinine) and hepatic enzymes are useful to monitor side effects of drugs either for FMS or a concomitant condition in Diagnosis of Fibromyalgia.

Although the prevalence of hypothyroidism does not seem increased in FMS compared with the normal population, We obtain T4 and thyroid-stimulating hormone levels in patients with significant fatigue, Even in the absence of other features of hypothyroidism.

Diagnosis:

Despite a common notion, Diagnosis of Fibromyalgia is disarmingly simple. It can, and should, be diagnosed by its own characteristics of widespread pain and multiple tender points; another concomitant condition, Such as arthritis or hypothyroidism, Does not exclude the Diagnosis of Fibromyalgia, as stated by the American College of Rheumatology (ACR) criteria. Putting it another way, if a patient has FMS as well as RA, This patient has both FMS and RA. Although the ACR criteria are for classification of FMS (So that researchers can use a uniform set of criteria for patient selection), These criteria have been found very useful for the Diagnosis of Fibromyalgia in clinical practice.

A patient with FMS may have many symptoms, But he or she needs only present with widespread pain and 11 or more tender points among the 18 sites specified in ACR criteria. Note that a patient with FMS may be tender in many more sites (Including Bones) besides these 18. Some patients have diffuse tenderness Everywhere on palpation. Such a phenomenon does not necessarily imply high psychological distress. Such diffuse tenderness on palpation or a significant psychiatric disease does not influence a Diagnosis of Fibromyalgia (as long as a patient satisfies the ACR criteria).

Now, a frequent question we hear from practicing physicians is, Should one diagnose FMS if a patient has widespread pain but not 11 tender points? For a clinical purpose, We suggest that a patient who has otherwise characteristic symptoms of FMS (e.g., Fatigue, Poor Sleep, Morning Fatigue, and one or more associated conditions) but only 6 to 10 tender points should be treated for FMS.

Differential Diagnosis:

Several conditions may mimic FMS. As emphasized before, a patient may have FMS as well as any of the conditions listed above. For example, Chest pain with localized tenderness in the chest wall in a patient with FMS would suggest the chest pain is part of FMS. However, This patient may also have a concurrent intrathoracic pathology the practitioner can diagnose by appropriate history, Physical Examination, and laboratory tests.

In another example of a concomitant disease, a 69-year-old female patient in our practice complained of pain and numbness in the legs when she first presented with FMS with a normal neurologic examination. Three years later, The pain as well as numbness in the legs became more intense. The pain was worse upon walking. This patient could no longer do her dishes standing because of bothering backache. Neurologic examination showed signs of L5-S1 root compression. A clinical diagnosis of spinal stenosis was made and we ordered an MRI scan of the lumbar spine. The MRI confirmed spinal stenosis that was treated surgically. The numbness and pain were substantially relieved following the surgery.

Diagnosis of Fibromyalgia:

Pathophysiologic Mechanisms of FMS:

Pathogenesis of FMS is incompletely understood. Despite muscle pain, No Histologic or biochemical abnormalities in the muscles have been demonstrated. Its now known that pain and fatigue, as well as several other symptoms, are central in origin, The most important mechanism being central sensitization.

Central sensitization. Neurons in the CNS undergo Structural, Chemical, and Functional changes following a peripheral noxious stimulus (Such as Mechanical, Chemical, or Thermal Injuries), Leading to heightened sensitivity of the neurons both at spinal and supraspinal levels. The process is called central sensitization with the following characteristics: an exaggerated response to a peripheral stimulus that's normally painful (Hyperalgesia); an experience of pain following a normally nonpainful stimulus,

Such as touch (allodynia); Persistence of pain; Greater intensity of pain (Which is also unpleasant); and wider distribution of pain than the area of original stimulation. A phenomenon related to central sensitization is called Wind-Up in animal models and temporal summation in humans. N-methyl-D-aspartate (NMDA) Receptors mediate this phenomenon. Its characterized by a progressive increase in pain secondary with each brief but repeated peripheral stimulus of the C fibers at a certain interval, For example, Two seconds. In Diagnosis of Fibromyalgia, However, There's no obvious peripheral tissue injury except Trauma-Induced inflammation (For example, From automobile accidents) in some patients.

So, The cause of nociceptor activation in a majority of these patients remains unclear. We have postulated that the CNS of some patients with FMS and similar disorders (Such as headaches and IBS) are inherently Hyper-Responsive Because of genetic susceptibility or childhood trauma or both. An otherwise in-apparent (Silent) Source of peripheral nociception, Such as mechanical stress in the cervical or lumbar spine, or such spinal stress generated by poor posture or degenerative disease, May now trigger central sensitization in these susceptible individuals.

Other sources of peripheral nociception, such as arthritis or a painful peripheral neurologic disease, May also initiate and perpetuate central sensitization. The presynaptic release of neurokinins mediate central sensitization, For example, Substance P (SP) and by excitatory amino acids, Such as glutamate and aspartate that activate postsynaptic NMDA receptors. As a result, Remarkable intramembranous and intracellular changes take place in the postsynaptic neurons, Such as alteration of cell membrane permeability, Influx of calcium, and activation of second messengers, all of which contribute to orchestrate marked neuronal changes leading to central sensitization.

Normally, There's also an inhibitory system that dampens hypersensitization. Serotonin, Norepinephrine, Endorphins, and other Neurochemicals mediate the inhibitory activities. However, the inhibitory system may be dysfunctional in central sensitization.

Evidence for Central Sensitization in FMS. Strong neurophysiologic evidence supports a state of central sensitization in FMS. One study demonstrated a significant reduction of the pain threshold in FMS patients compared with normal controls following an innocuous electrocutaneous stimulation that was associated with unpleasant pain, dysesthesia, and anatomical spread of pain. Other examples of central sensitization have been summarized and include temporal summation, decreased cerebral blood flow in the caudate nucleus and thalamus by single-photon emission computed tomography, and augmented pain processing.

Theres also central Sensitivity-Related Neurochemical disturbance in FMS, e.g., Increased SP and decreased 5-Hydroxyindole acetic acid (5-HIAA, a metabolite of serotonin) in the cerebrospinal fluid and decreased serum serotonin. Both increased SP and decreased serotonin help to explain increased pain sensitivity in Diagnosis of Fibromyalgia.

Endocrine aberrations. Neuroendocrine abnormalities may play an important role in FMS. These include Hypothalamic-Pituitary-Adrenal (HPA) axis disturbance with an exaggerated adrenocorticotropin (ACTH) response to Corticotropin-Releasing hormone with normal cortisol response. Relative hypocortisolemia in FMS is not due to a primary failure of the adrenal cortex and seems to be of hypothalamic origin. Note that these findings are different from those found in depression where hyperreactivity of the HPA axis has been demonstrated at all levels, Including Hypercortisolemia that escapes Dexamethasone suppression. Growth hormone (GH) deficiency in FMS may partly explain a lack of energy among patients with FMS. GH is secreted mostly during Non-Rapid eye movement (REM) sleep, which is disturbed in FMS.

Nonrestorative Sleep. Most patients with FMS sleep poorly and wake up tired in the morning. Alpha intrusion of non-REM sleep in FMS indicates arousals during the restorative phase of sleep architecture. Phasic alpha sleep, in particular, is associated with increased pain and tender points the next morning. However, routine sleep electroencephalographic testing has no practical utility unless other sleep problems, e.g., REM sleep behavior disorder and sleep apnea, are clinically suspected. Poor sleep the previous night predicts pain the next day.

Psychological Factors. Psychological distress aggravates pain and fatigue in FMS. Most studies have shown an increased frequency of present and lifetime anxiety, Stress, and depression in patients with FMS compared with normal as well as RA control groups. Poor coping skills may also perpetuate pain. However, Its clear that psychological factors aren't necessary in causing FMS. Only about 30 to 40 percent of patients have psychological disturbance, and in many of these cases, distress may be secondary to chronic pain itself.

Genetic Factors. Genetics is quite likely to play a role in FMS. There's familial aggregation in FMS. Genetic markers include T102C polymorphism of the 5-HT2-A receptor gene and a probable linkage with the HLA. Genome mapping of multicase families with FMS is currently in progress.

Summary of Pathophysiologic Mechanisms. FMS is a multifactorial condition with many triggering or interacting factors, Such as genetics, Neuroendocrine aberrations, Psychological distress, Trauma, Peripheral sources of nociception (For example, Inflammation), Poor sleep, Deconditioning, or Overactivities, Which may initiate and sustain central sensitization leading to chronic pain and exaggerated response to various stimuli. Its now clear that FMS symptoms may be explained by biological and Psychosocial-Behavioral factors, With much variability in the relative contributions of these elements in an individual patient.

Central Sensitivity Syndromes (CSS):

Yunus was the first to postulate and demonstrate that several common chronic illnesses, Such as fibromyalgia, IBS, Headaches, and primary Dysmenorrhea, are related conditions with many similar features with a common pathophysiology. These are currently called Functional somatic syndromes, an intriguing name for a group of disorders that manifest as dysfunction in the neuroendocrine systems. It now seems that the common binding pathophysiologic glue of these conditions is central sensitization; Hence the term Central Sensitivity or CSS. CSSs include FMS, IBS, Chronic Fatigue Syndrome, Myofascial Pain Syndrome, Restless legs syndrome, Temporomandibular dysfunction syndromes, Multiple chemical sensitivity, Post-Traumatic stress disorder, Depression, and other similar conditions.

Diagnosis of Fibromyalgia:

Clinical Highlights:
?Common sites of pain or stiffness in patients with fibromyalgia syndrome (FMS) are Low back, Neck, Shoulders, Arms, Hands, Knees, Hips, Thighs, Legs, and Feet. Chest pain is not uncommon and tender points in the chest wall may accompanied it. Fatigue is a frequent manifestation and may be the presenting feature in some patients because of its severity.
? The diagnostic finding in FMS is multiple tender points (11 or more among the 18 sites specified by the American College of Rheumatology [ACR] criteria). However, if a patient with characteristic symptoms (For example, Pain in many sites, Fatigue, Poor sleep, Morning fatigue) Has only 6 to 10 tender points, Treat that patient as if he or she has FMS.
? Examination of the joints shows no objective swelling; However, Some patients have marked joint tenderness on palpation. Neurologic examination results are normal in FMS.
?Psychological factors alone do not cause FMS, Although anxiety, Stress, and depression may contribute to, or exacerbate, Pain and fatigue. In many patients, Distress may be secondary to chronic pain.
? Laboratory testing isn't required to make the diagnosis of FMS, Because the disorder is identifiable by using ACR criteria that state that FMS is not a disease of exclusion. Order laboratory tests such as radiographs, Antinuclear antibody, or rheumatoid factor only if the history and physical examination results suggest a concomitant condition.

ARTICLE SOURCE: We have not modified the factual content from the article by By Sule Arslan, MD, Gaziosmanpasa University, and Muhammad B. Yunus, MD, University of Illinois. This content is syndicated news that you can use for your research, and we hope that it can help your productivity. This content is strictly for educational purposes and is not made for any kind of commercial purposes of this blog.

 

Cervical Cancer Remains One of the Most Prevalent Diseases

Cervical Cancer Remains One of the Most Prevalent Diseases

Cervical Cancer Remains One of the Most Prevalent Diseases

Cervical Cancer

ABSTRACT: Cervical cancer remains one of the most prevalent diseases affecting women worldwide. Essentially, the human papillomavirus (HPV) infection causes all cervical cancer, and two high-risk subtypes, HPV 16 and HPV 18, account for about 70 percent of all cases. Risk factors include multiple sex partners, early age at first intercourse, multiparity, immuno-deficiency, and smoking. Screening programs for cervical cancer in the United States have markedly reduced the incidence of the disease.

The Papanicolaou test (Pap test) has been the mainstay of screening; liquid-based cytology is the most common. HPV testing has two major roles in the clinical setting: triage of atypical squamous cells of undetermined significance (ASC-US) cytology and combination screening in patients older than 30 years. Prevention of cervical cancer involves not only screening but also education, safe sexual practices, and use of the HPV vaccines.

The introduction of human papillomavirus (HPV) vaccines and the availability of a DNA test for the virus are exciting developments in the detection and prevention of cervical cancer. They represent a unique opportunity to continue to reduce the number of cases of cervical cancer in the United States and worldwide.

Epidemiology:

Cervical cancer remains one of the most prevalent diseases affecting women worldwide, second only to breast cancer in terms of malignancy-related morbidity and mortality. Worldwide, cervical cancer continues to affect more than 530,000 women annually and results in more than 275,000 deaths.

In the United States, screening programs have markedly reduced the incidence and prevalence of cervical cancer over the past 50 years. The American Cancer Society estimates that there will be about 12,170 new cases of invasive cervical cancer in the United States in 2012, with 4220 deaths. In addition, the lifetime probability that an American woman will develop cervical cancer is approximately 1 in 147.

Risk Factors:

Many risk factors contribute to the development of cervical cancer. Its now known that essentially HPV causes all cervical cancer. This virus is transmitted sexually, and although HPV infection is not a re-portable disease, its estimated to be the most common or second most common sexually transmitted infection in the United States. Management of risk factors primarily involves lessening the risk of HPV transmission.

Modification of sexual behavior is the best way to prevent HPV infection and cervical cancer. Patients with multiple partners are at greater risk for the development of cervical cancer; in fact, those patients with seven or more partners have a relative risk of 8.1. Patients who engage in intercourse at a younger age or with more high-risk sex partners are also at greater risk for the development of cervical cancer. Other sexually transmitted infections, such as chlamydia, may also be co-factors in the development of invasive cervical cancer.

Multiparity is an additional known risk factor, although the physiologic reason for the increased risk is not clear. The increased risk may stem from the vaginal trauma during delivery, the effects of the hormone changes on the cervix, or nutritional variations during pregnancy. Immunodeficiency, either secondary to systemic disease such as HIV infection or long-term immunosuppressant medications, also increases the risk of cervical cancer. Screening intervals and strategies should reflect this increased risk. Theres also some evidence that long-term (greater than five years) use of oral contraceptives increases the risk of cervical cancer in patients who test positive for HPV.

Smoking has been shown in numerous studies to be a co-factor in the development of cervical cancer. Among HPV-positive patients, the risk increases for those who have ever smoked. Although the definite cause of this association isn't clear, the cervical mucus of smokers reveal metabolites of cigarette smoke, where these metalbolites likely damage host cell DNA and facilitate cervical cancer progression.

HPV can be found in approximately 99.7 percent of all HPV infections. This family of double-stranded DNA viruses includes more than 100 subtypes. The viruses infect only humans, and they have a variety of clinical manifestations. In addition to cervical cancer, HPV causes common warts, plantar warts, genital warts, and Bowens disease.

Certain subtypes have been implicated in the development of cervical cancer. The subtypes that cause cancer are stratified into low-, high-, and intermediate-risk groups. Most of the attention focuses on the most high-risk subtypes, especially HPV 16 and HPV 18. These two high-risk types account for about 70 percent of all cervical cancer.

HPV infection is extremely common in young sexually active women. One study found a prevalence of 64 percent among urban adolescent girls, while the overall prevalence among women aged 18 to 40 years is 40 percent. Typically, young women acquire the infection during their late teenage or college years. A study of college-age women showed that 43 percent of those who were initially HPV-negative tested positive for the virus within the next three years.

HPV is transmitted through skin to skin contact, the majority of which is intimate contact or intercourse. The transmission of HPV subtypes may be genital-genital, oral-genital, or manual-genital. Fomite transmission, though unlikely, is possible. Most HPV infections clear within 24 to 36 months, especially in younger women.

HPV causes cervical cancer by incorporating into the host DNA. The oncogenes E6 and E7 incorporate into host DNA and encode proteins that then interact with host proteins to dysregulate the cell cycle.

Screening Methods:

Screening programs for cervical cancer in the United States have markedly reduced the incidence of the disease. Because cervical cancer arises from a precancerous state, cervical intra-epithelial neoplasia (CIN), we are able to detect and appropriately treat these changes before invasive cervical cancer develops. From the detection of CIN class 2 or 3, it takes an average of about 10 years for invasive cervical cancer to develop. This lead time allows detection and treatment for most cases in the early stages.

Although screening programs are very successful, the current system still has inadequacies and inefficiencies. In 2010, 76.4 percent of adult women reported having a Papanicolaou (Pap) test in the past three years. Most commonly, cervical cancer develops because a patient had no screening at all or missed screening tests.

Papanicolaou Test. Cervical cancer screening has had widespread use in the United States since the 1950s. Dr. George Papanicolaou originally developed the Pap smear in 1941. A standardized reporting system, the Bethesda System, was developed in 1988 and revised in 2001.

The conventional Pap smear has some disadvantages. The test has a low sensitivity of 60 percent to 80 percent, and therefore annual testing was necessary to increase the likelihood of detecting early cervical changes. The test itself also has inherent disadvantages, since it requires individual interpretation by cytopathologists. In addition, the quality of the samples collected is highly variable, and the differentiation of the cell types can be technically difficult.

Most cytology done in the United States today is liquid-based cytology. As opposed to smearing the cells directly onto a microscope slide, the cells are placed into a vial with preservative liquid and processed to separate the cells from the microscopic debris. The sensitivity of the liquid-based test has been reported to be 85 percent to 95 percent. Another benefit of the liquid-based testing is that the remainder of the sample can be used for additional testing for HPV, chlamydia, or Neisseria gonorrhoeae. Use of the liquid-based test reduces the false-negative rate by 60 percent.

HPV DNA Test. The newest test available for screening is the HPV DNA test. This test screens for the 13 high-risk HPV subtypes that are most likely to cause cervical cancer. The test employs RNA probes that bind to the HPV DNA strand. Antibodies then capture the hybrids and produce light, which is measurable. This test is more sensitive (88 percent to 100 percent) than cytology methods but is also less specific for the detection of cervical dysplasia.

HPV testing basically has two major roles in the clinical setting:

  • Triage of atypical squamous cells of undetermined significance (ASC-US) cytology
  • Combination screening in patients older than 30 years

The HPV DNA test has some advantages, including increased sensitivity (up to 100 percent), the lack of inter-observer variability, and the possibility for self-collection. Disadvantages to the test include the high prevalence of the disease, especially in women younger than 30 years. In addition, a test with high sensitivity and relatively lower specificity for high-grade squamous intra-epithelial lesion (HSIL) (86 percent) could lead to increased false-positive tests and more colposcopy. Moreover, in younger women, a majority of the HPV infections are transient and will be cleared by the immune system without any appreciable cellular cervical changes.

For women older than 30 years of age among whom the prevalence of HPV infection is lower than in younger women, but the infections are less transient the HPV DNA test in combination with liquid-based cytology has a negative predictive value of 99 percent to 100 percent, and the likelihood that the patient has undetected CIN 2 or higher is 1 in 1000. This approach is also cost-effective.

The HPV DNA test has an important role in the triage of patients with ASC-US cytology on conventional or liquid-based tests. A large, multicenter trial from the National Cancer Institute, the Atypical Squamous Cells of Undetermined Significance/Low Grade Squamous Intraepithelial Lesion Triage Study (ATLS), ended in 2001. This study randomized patients with ASC-US or low-grade squamous intra-epithelial lesion (LSIL) to one of three management arms: HPV DNA testing, immediate colposcopy, or repeated cytology. This study found that HPV testing was more sensitive for CIN 2 or 3 and fewer patients were referred for colposcopy.

In order for patients and physicians to adopt new screening practices involving the HPV test, we need to correct some of the myths about the virus, the infection, and the test. First, the infection is extremely common and affects more than 80 percent of women at some point in their lives. Patients also need to know that most positive HPV infections are transient, and that the immune system will clear most infections without any additional treatment. Patient education should also emphasize that a positive HPV test does not indicate unfaithfulness in a relationship.

Guidelines for Screening:

The table [See original article] lists the three major cervical cancer screening guidelines issued by the American Cancer Society (ACS), the United States Preventive Services Task Force (USPSTF), and the American College of Obstetrics and Gynecology (ACOG).

All of the current guidelines recommend initiation of screening at age 21 regardless of sexual history. Although screening for patients who are truly abstinent isnt necessary, screening patients older than age 21 ensures the screening of women with either incomplete or unreliable sexual histories. We don't recommend screening those younger than age 21 because adolescents are at very low risk for cervical cancer and any cervical cell abnormalities detected are probably transient and will resolve on their own.

Annual screening is no longer recommended. The USPSTF and the ACS recommend screening women ages 21 to 65 with the Pap test every three years. Women ages 30 to 65 can be screened with the HPV DNA test and the Pap test (co-testing) every five years. In this age group, the ACS preferred co-testing over the Pap test alone, whereas the USPSTF considered co-testing an acceptable alternative. All current guidelines advise against using the HPV DNA test alone in women of any age or using co-testing in women younger than 30 years.

ACOG recommends screening women ages 21 to 29 with the Pap test every two years; women ages 30 to 65 may increase the interval between Pap tests to every three years if they have a history of three consecutive negative Pap tests. Co-testing is acceptable in women ages 30 to 65 every three years if the Pap test is normal and the HPV test is negative.

All current guidelines have exceptions for patients who are at increased risk for cervical cancer, including those who are immuno-compromised or have a history of cervical dysplasia or cancer.

The recommendations vary with regards to the discontinuation of screening, ranging from 65 years (USPSTF and ACS) to 70 years (ACOG) depending on the results of previous tests. ACOG recommended the continuation of routine screening in older women who have multiple sex partners. A total hysterectomy is also a reason to discontinue screening, but the reason for the surgery (benign versus malignant conditions) should dictate the necessity of screening.

For example, depending on risk factors, sampling of cells in the vaginal vault may be done to screen for vaginal cancers and/or confirm the absence of any remnant cervical cells. Pap tests should continue after a supra-cervical hysterectomy (cervix remains). In either case, regular pelvic and rectal examinations are necessary. Women who have received the HPV vaccine should continue screening because the overall effect of vaccination on high-grade precancerous cervical lesions and cervical cancer remains unknown.

Risk Management:

Incorporating the HPV test into a primary screening role in conjunction with Pap testing could also prove to be a wise risk management decision. Although the Pap test has been an extremely effective screening tool, the test still has some inherent legal risks. There are several steps in Pap testing that increase the likelihood of error. First, the tests require collecting an adequate sample, and invariably the samples are of inconsistent quality. Then, cytopathologist, whos reading up to 100 slides per day, needs analyze and read the tests. There are additional steps in physician and patient notification of results and appropriate follow-up testing that make the Pap test an imperfect test.

Beyond the potential pitfalls in performing the Pap test, physicians must realize that most women believe the test is 100 percent accurate even though there are significant false-negatives. In addition, if a patient does develop cervical cancer and the screening protocol wasn't followed closely or there was an error, most juries will empathize with a young otherwise healthy patient. The HPV test has higher sensitivity, does not rely on human interpretation, and leaves less room for error and potential malpractice claims.

Prevention:

Prevention of cervical cancer certainly involves screening, but it also includes education, safe sexual practices, and HPV vaccination. At this point, abstinence is the only certain way to prevent the acquisition of the HPV subtypes that lead to cervical cancer. Long-term monogamous relationships also play a role in the prevention of the spread of the virus, because patients with multiple partners are at increased risk for HPV infection.

Although condoms are not entirely effective at preventing the transmission of HPV, they do appear to decrease the likelihood of developing a genital HPV infection. A study of 82 college-age women engaging in their first sexual intercourse showed a significantly lower incidence of HPV infection in those whose partners used condoms 100 percent of the time. These patients also had no cases of intra-epithelial lesions during the course of the study. Another study showed that proper condom use facilitates the clearance of an HPV infection.

The most significant development in the prevention of HPV infection and cervical cancer has been the HPV vaccine. Two vaccines have received approval for the prevention of the most common types of HPV infection that cause cervical cancer: Gardasil and Cervarix.

In 2006, the FDA approved the use of Gardasil for girls and women ages 9 to 26. This quadrivalent vaccine is designed to prevent infection with HPV 6, 11, 16, and 18. HPV 16 and 18 cause about 70 percent of all cases of cervical cancer, and HPV 6 and 11 are subtypes responsible for genital warts. The vaccine uses the viral capsid protein (L1) and does not include any HPV DNA. The phase IIb trial of this quadrivalent vaccine showed an efficacy of 90 percent with regard to persistent infection or disease associated with any of the 4 subtypes (6, 11, 16, 18) through 36 months. Gardasil is also approved for use in boys and men ages 9 to 26.

In 2009, the FDA approved the use of Cervarix for girls and women ages 10 through 25 years; this bivalent vaccine was developed to prevent HPV 16 and 18 infections. The study of the bivalent vaccine enrolled 1113 women and was shown to be effective at reducing persistent infections with HPV 16 and HPV 18 in 100 percent of patients.

The CDCs Advisory Committee on Immunization Practices recommends routine vaccination of girls aged 11 or 12 years with three doses of either Cervarix or Gardasil. The vaccination series can be started beginning at age 9. Vaccination is also recommended for girls and women aged 13 through 26 years who have not received vaccinations previously or who have not completed the three-dose series.

If a woman reaches age 26 before the vaccination series is complete, remaining doses can continue after age 26. The CDC also recommends Gardasil for all boys age 11 or 12, and for males 13 through 21 who did not get any or all of the three doses when they were younger. All men, including those who have sex with other men (e.g., bisexual men), may receive the vaccine through age 26 if they did not get fully vaccinated when they were younger.

Ideally, the vaccine should be administered before potential exposure to HPV through sexual contact. The median age of first sexual intercourse in the United States is 15 years, so the recommended age range for vaccination would capture most patients before their initial sexual encounter.

These vaccines could drastically reduce the number of biopsies and invasive procedures associated with abnormal Pap and HPV tests; however, routine cervical cancer screening remains important. The screening will be necessary to prevent cancer in patients who did not receive the vaccine, who had HPV before they were vaccinated, or who are infected with other HPV subtypes. In addition, the long-term efficacy of the vaccines has not been established.

The acceptance of the HPV vaccine by physicians, patients, and parents is also a concern. Although the initiation of the HPV vaccination series among girls in the United States aged 13 to 17 years increased from 25 percent in 2007 to 48.7 percent in 2010, only one in three completed the entire three-dose series. Furthermore, a recent study showed that the number of insured females aged 13 to 27 years completing the HPV vaccination series dropped overall from 50 percent in 2006 to approximately 20 percent in 2009.

The study also found that obstetricians/gynecologists were more successful in having patients complete the series compared to pediatricians and family medicine practitioners, with family medicine practitioners the least successful. Because the infection is sexually transmitted, continued education about cervical cancer and HPV is necessary to convince people of the efficacy and appropriateness of the vaccine, especially in the preteen population before sexual activity occurs.

ARTICLE SOURCE: We have not modified the factual content on cervical cancer from the source. This content is syndicated news that can be used for your research, and we hope that it can help your productivity. This content is strictly for educational purposes and is not made for any kind of commercial purposes of this blog.

Dr. John Whyte, MD, MPH, is a former medical advisor at the U.S. Department of Health and Human Services in Washington, D.C., and director of the Secretary's Council on Private Sector Initiatives. He's currently the chief medical expert and vice president, health, and medical education, at Discovery Channel in Silver Spring, MD.

Know About the Mercury Levels in Fish

Know About the Mercury Levels in Fish

Mercury Levels

We know that fish is very nutritious and packed with great nutrients such as omega-3, the B vitamins, and lean protein. Unfortunately, though, fish can also have some unhealthy contaminants. Mercury levels in fish probably present the greatest concern.
Know about the Mercury Levels In Fish

Mercury is a contaminant found in fish that can affect brain development and the nervous system. The FDA has guidelines for children, women who are pregnant, and women who are trying to become pregnant. These guidelines state you should consume no more than 12 ounces of low-mercury fish weekly. Avoid highest-level-mercury fish and keep high-level-mercury fish to only three six-ounce servings per month.

What does this mean for women who are pregnant but also trying to get some of their much-needed nutrients from the critters of the sea? Its all about moderation. Recent information found in the American Journal of Preventive Medicine says that no one should eliminate fish out of the diet altogether. Fish contains too many healthy nutrients that are essential for growth and development, especially in a pregnant mom or baby. You should avoid four types of fish due to mercury levels. These include shark, king mackerel, swordfish, and tilefish.

For information regarding other types of fish, the Natural Resources Defense Council (NRDC) has a list of fish and their mercury levels so that people can know what theyre consuming. If you want to get more detailed information about mercury levels and how much you personally consume, you can also use the mercury thermometer to calculate your totals.

Mercury Levels in Fish

Highest Mercury

AVOID Eating

  • Marlin
  • Orange roughy
  • Tilefish
  • Swordfish
  • Shark
  • Mackerel (King)
  • Tuna (Bigeye, Ahi)

High Mercury

Eat no more than three six-ounce servings per month.

  • Sea Bass (Chilean)
  • Bluefish
  • Grouper
  • Mackeral (Spanish, Gulf)
  • Tuna (Canned, White Albacore) See Tuna Chart Below
  • Tuna (Yellowfin)

Lower Mercury

Eat no more than six six-ounce servings per month.

  • Bass (Striped, Black)
  • Carp
  • Cod (Alaskan)
  • Croaker (White Pacific)
  • Halibut (Pacific and Atlantic), Jack smelt (Silverside)
  • Lobster
  • Mahi Mahi
  • Monkfish
  • Perch (Freshwater)
  • Sablefish
  • Skate
  • Snapper
  • Sea trout (Weakfish)
  • Tuna (Canned, Chunk Light)
  • Tuna (Skipjack)

Lowest Mercury

Enjoy two six-ounce servings per week.

  • Anchovies
  • Butterfish
  • Catfish
  • Clam
  • Crab (Domestic)
  • Crawfish/Crayfish
  • Croaker
  • Flounder
  • Haddock
  • Hake
  • Herring
  • Mackeral (North Atlantic, Chub)
  • Mullet
  • Oysters
  • Perch (Ocean)
  • Plaice
  • Salmon (Canned, Fresh)
  • Sardines
  • Scallops
  • Shad (American)
  • Shrimp
  • Sole
  • Squid (Calamari)
  • Tilapia
  • Trout (Freshwater)
  • Whitefish
  • Whiting

(Chart from the Natural Resource Defense Council (NRDC); Data obtained by the FDA and the EPA)

Tuna mercury levels can differ based on the type of tuna and where it was caught. The NRDC created the chart below as a guideline to how much tuna children, pregnant women or women wanting to conceive can eat, based on their weight.

Weight in Pounds Frequency
White Albacore Chunk Light

20 lbs 1 Can/10 Weeks 1 Can/3 Weeks
30 lbs 1 Can/6 Weeks 1 Can/2 Weeks
40 lbs 1 Can/5 Weeks 1 Can/11 Days
50 lbs 1 Can/4 Weeks 1 Can/9 Days
60 lbs 1 Can/3 Weeks 1 Can/7 Days
70 lbs 1 Can/3 Weeks 1 Can/6 Days
80 lbs 1 Can/2 Weeks 1 Can/ 6 Days
90 lbs 1 Can/2 Weeks 1 Can/5 Days
100 lbs 1 Can/2 Weeks 1 Can/5 Days
110 lbs 1 Can/12 Days 1 Can/4 Days
120 lbs 1 Can/11 Days 1 Can/4 Days
130 lbs 1 Can/10 Days 1 Can/4 Days
140 lbs 1 Can/10 Days 1 Can/3 Days
150 lbs+ 1 Can/9 Days 1 Can/3 Days

Article Source: We have not modified the factual content about mercury levels in fish from the source. This content is syndicated news that you can be use for your research, and we hope it can help your productivity. This content is strictly for educational purposes and is not made for any kind of commercial purposes of this blog.

Dry Skin? Are You Putting Oil on the Wrong Side?

Dry Skin? Are You Putting Oil on the Wrong Side?

Dry Skin? Are You Putting Oil on the Wrong Side?

In an attempt to fend off Dry Skin, Fine Lines, Wrinkles and Eczema, The average woman will spend nearly $28,000 on topical face and skin moisturizers during her lifetime. While these topical moisturizers are designed to temporarily relieve the uncomfortable itching and tightness of dry skin, Most people use them in an unsuccessful attempt to prevent Wrinkles, Flaking, and Redness associated with Dry Skin.

ojos-2-1251211While millions of men and women reach for over-the-counter moisturizers to address the issues associated with Eczema and Dry Skin, Research demonstrates that the most effective way to treat these issues is from the inside - starting with High-Quality Omega-3 Fatty Acids.

Dry Skin and Eczema: Major Symptoms of Omega-3 Deficiency

Omega-3 fatty acids are essential for proper functioning of the organs, including the skin. An Omega-3 deficiency results in some pretty clear physical symptoms, including:

  • Dry, Rough, Bumpy Skin
  • Cracks in Skin (Including the Heels and Feet)
  • Eczema, (Especially on the back of the Arm)
  • Flaking and Scaling of Skin
  • Dry Hair and Dandruff

Omega-3s are also essential for neurotransmitters in the brain to function at optimal levels. Low levels of Omega-3 can also result in:

  • Attention and Memory Issues (Loss of Memory, Inability to Concentrate, Poor Decision Making, Easily Distracted)
  • Emotional Issues (Frequent Mood Swings, Anxiety, and Mild to Severe Depression)

Omega-3 Improves Healthy Skin and Brain Health

Omega-3 deficiency is a common condition in the US with over 90% of the population thought to be omega-3 deficient. The body requires adequate amounts of both EPA and DHA (Found in Omega-3 Fatty Acids) to maintain optimum health; Unable to produce these in the body, You must consume Omega-3 from various food sources.

While large amounts of Omega-3 can be found in various types of Cold-Water, Oily Fish, Large scale pollution has lessened the viability of fish as a whole food solution. Many experts recommend treating skin issues with a high-quality Omega-3 Supplement.

High-Quality Omega-3 Fatty Acids provide appropriate needed levels of fats to the skin while also preventing dehydration at the cellular level. The added fats and water in skin cells resulting from increased levels of Omega-3 Fatty Acids drastically improve skin health, including:

  • Easing Inflammation
  • Improving the Symptoms Associated with Eczema
  • Lessening the Development of Fine Lines and Wrinkles
  • Softer Skin
  • Preventing Flaking and Dandruff

Adding a high-quality source of DHEA-Rich Omega-3 Fatty Acid, Usually through supplementation with fish oil or krill oil, is also a proven natural treatment for Postpartum, Anxiety, and Depression.

Improving Dry Skin Is Easier Than Ever Before

Supplementing with Omega-3 Fatty Acids is easier than ever before. High-Quality sources of Omega-3 Fatty Acids are now available in Blends of Omega Oils, Easy to Swallow Traditional Capsules, and evenGreat-Tasting Omega-3 Emulsions. Other, more specific types of omega products, including those rich in DHEA and EPAand Krill Oil, are also available.

Preventing dry skin (and saving thousands of dollars at the beauty counter) can easily be accomplished by supplementing with Omega-3 Fatty Acids. Most people see noted improvement in skin health by supplementing with the equivalent of just one to two tablespoon of Omega-3 each day.

If you are not supplementing with Omega-3 Fatty Acids, Do your Skin a Favor and Start Today!

MTHFR FAQ

MTHFR FAQs

We get many calls at our office about MTHFR, so here are the common questions and our answers.

1. What ICD9 code do you use for MTHFR?

Ans. We havent found a specific code for MTHFR, but we use 270.4. This is the code that comes up on ICD9Data.com search. There is a second code 270.9 which is an unspecified disorder of amino-acid metabolism could be used, but we believe 270.4 is the best code to use.

We change the standard description which is listed below from ICD9Data.com to MTHFR in our medical record system. We also denote the type and whether it is is hetero or homozygous. For example our coding would be 270.4 MTHFR 677 heterozygous or MTHFR 677/1298 compound heterozygous.

Definition of 270.4 code

Disturbances of Sulphur-Bearing Amino-Acid Metabolism

  • Autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of cystathionine beta-synthase and associated with elevations of homocysteine in plasma and urine; clinical features include a tall, slender habitus, scoliosis, arachnodactyly, muscle weakness, genu varis, thin blond hair, malar flush, lens dislocations, an increased incidence of mental retardation, and a tendency to develop fibrosis of arteries, frequently complicated by cerebrovascular accidents and myocardial infarction.
  • Short description: Sulph amino-acid met dis.
  • ICD-9-CM 270.4 is a billable medical code that can be used to specify a diagnosis on a reimbursement claim.

We take out that description and put in MTHFR or MTHFR 677 heterozygous, MTHFR compound heterozygous 677/1298, or MTHFR 1298 homozygous. The detail is useful in the problem list, since we treat different variations differently.

2. Do Insurance companies pay for MTHFR testing?

Ans. Unfortunately, the answer is often no, but that has been changing we are seeing more and more insurance carriers pay for this testing. They certainly should since methylation issues are treatable and treatment can help mitigate or prevent much more expensive problems both immediately and in the future.

3. Do you treat all MTHFR anomalies the same way?

Ans. No, when the 677 variant is present we have found that L-methyl folate (Deplin) works best. We use methyl B12 when the 1298 variant is present.

4. Can you expect side effects with the use of Deplin or L-methyl folate?

Ans. Yes, there are several common side effects. Deplin can cause an upset stomach in some people is taken on an empty stomach. If the Deplin dose is too high, it may cause the body to dump excessive amounts of toxins into the system. This can cause side effects. These can be reduced or eliminated in most cases by using a binding agent to bind up toxic bile being released by the liver or starting at a lower dose and working up to the maintenance dose.

5. I Looked up Deplin and it is used for depression and I dont have depression should I still take Deplin?

Ans. If you have a MTHFR 677 anomaly, then you will benefit from L-methyl folate (Deplin). The FDA is fairly simplistic in their thinking, which is one diagnosis, one drug. If you are want to use it for something else, then according to the FDAs way of thinking you need a different drug name. For example Zyban (bupropion) is a drug to help with smoking cessation, the exact same medication is used as anti-depressant under several different trade names: Wellbutrin, Voxra, Budeprion, Prexaton, Elontril or Aplenzin.

Physicians understand that a drug may be used for multiple medical problems, this is called off label prescribing. FDA has approved Deplin as a medical food that has demonstrated benefit for the treatment of depression. This does not mean Deplin is only useful for depression. The main reason for using Deplin when MTHFR is present is because it helps methylation and indirectly raises glutathione. Low glutathione is the root cause of many chronic illnesses.

6. Are over the counter versions of methyl folate just the same as the brand name Deplin?

Ans. For the most part the answer is no, with some exceptions. There are racemic versions of methyl folate being marketed as equivalent to L-methyl folate (Deplin). They are not. The racemic versions contain both D-methyl folate and L-methyl folate. The D-methyl folate (non active form of folic acid) can compete at the binding site making the L-methyl folate less effective. There are some forms L-methyl folate being marketed OTC.

Definition of racemic: Of, relating to, or constituting a compound or mixture that is composed of equal amounts of dextrorotatory and levorotatory forms of the same compound and is not optically active.

7: What is a SNP?

Web definitions:

A single-nucleotide polymorphism (SNP, pronounced snip; plural snips) is a DNA sequence variation occurring when a single nucleotide - A, T, C or G - in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes in a human.

Single nucleotide polymorphism abbreviated as SNP and pronounced snips. Means one nucleotide or setting on the gene has a variation from the normal. For example in the diagram below MTHFR 1298C is GT instead of TT. The letters refer to one of the 4 bases that make up the DNA code. If you are getting lost now, then check out the Genetic Science Learning Center below.

The University of Utah Genetic Science Learning Center has an excellent resource that it helps you understand this complex genetic nomenclature and the health significance of these SNPs.

8. What is most affordable way to get MTHFR testing?

Ans. If it is covered by your insurance and that is a big if, that is usually the most affordable way to go, but it requires a physician request. In our office if patients are not in hurry a much better solution is through a genetic testing company.

They offer a much broader profile for $99.00. The only problem is the data is not found in the report. However, two other websites will convert the 23andme data into the form used by physicians for a nominal fee or a donation. Currently, it is taking about two months to get the report back.

We then use Livewello, which charges $20 and you get a nice easy to read color coded report with the data presented using nomenclature familiar to physicians, such as MTHFR 677 rather than rs1801133, which referred to as the rsID. The rsID is useful since many databases use this nomenclature for categorizing information on different genetic snps. See the NIH snp database called dbSNP.

The Livewello data comes in report the looks like this. This is just a small portion of the report. The report is color coded: green means normal, yellow is heterozygous, and red is homozygous. In the second report I have highlighted the MTHFR 677 and MTHFR 1298 snps, which are both yellow, so this individual is compound heterozygous 677/1298. However, you can see from the report that there are other areas of concern.

LivewelloMTHFoutput.LivewelloMTHFoutput2

The table below is the same data copied in spreadsheet format. The links are live and will take you to SNPopedia, which has more detailed information on that SNP.

METHYLATION 3Gene & VariationrsIDRisk AlleleYour AllelesResultsGIF (TCN3)rs558660AAG+/-MAO A R297Rrs6323GT-/-MTHFD1 C105Trs1076991TCT+/-MTHFD1 G1958Ars2236225AAG+/-MTHFR 03 P39Prs2066470AAG+/-MTHFR A1298Crs1801131GGT+/-MTHFR A1572Grs17367504GAG+/-MTHFR C677Trs1801133AAG+/-MTHFR G1793A (R594Q)rs2274976TCT+/-MTR A2756Grs1805087GAA-/-MTRR A66Grs1801394GAA-/-MTRR H595Yrs10380TCT+/-MTRR K350Ars162036GAG+/-MTRR R415Trs2287780TCC-/-MTRR-11 A664Ars1802059AAG+/-NOS1rs3782206TCC-/-NOS2rs2297518AAG+/-NOS2rs2274894TGG-/-NOS2rs2248814AGG-/-NOS3rs1800783AAT+/-NOS3rs1800779GAG+/-NOS3rs3918188AAC+/-