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Friday, July 1, 2016

Factitious Graves' disease due to biotin immunoassay interference - A case and review of the literature


                                                                  
  

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Elston MS, et al. J Clin Endocrinol Metab. 2016.

Abstract

CONTEXT: Biotin (Vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30μ g per day. Low-moderate dose biotin is a common component of multivitamin preparations and high dose biotin (10,000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays and supplementation may cause interference in both thyroid and non-thyroid immunoassays.
OBJECTIVE: To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference Design: We report a patient with biotin-associated abnormal TFTs, and a systematic review of the literature Setting: A tertiary endocrine service in Hamilton, New Zealand Results: The patient had markedly abnormal thyroid function tests that did not match the clinical context. Following biotin cessation, TFTs normalised far more rapidly than possible given the half-life of thyroxine, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin.
CONCLUSION: Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

PMID

 27362288 [PubMed - as supplied by publisher]

full report found here






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Dietary Inflammatory Index and Risk of Multiple Sclerosis in a Case-Control Study from Iran.


                                                                  
  

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Abstract

BACKGROUND: Diet and inflammation have been suggested to be important risk factors for multiple sclerosis (MS).
OBJECTIVES: In this study, we examined the ability of the dietary inflammatory index (DII) to predict MS in a case-control study conducted in Iran.
METHODS: This study included 68 MS cases and 140 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Logistic regression models were used to estimate ORs adjusted for age, energy, sex, body mass index, season of birth, rubella history, history of routine exercise before MS, smoking and history of consumption of cow's milk in the first 2 years of life.
RESULTS: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of MS, with the DII being used both as a continuous variable (ORcontinuous 1.66; 95% CI 1.19-2.31; 1 unit increase corresponding to ≈15% of its range in the current study) and a categorical variable (ORDII (>1.43 vs.≤1.43) 2.68; 95% CI 1.15-6.26).
CONCLUSIONS: These results indicate that a pro-inflammatory diet is associated with increased risk of MS.
© 2016 S. Karger AG, Basel.







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High Intensity Aerobic and Resistance Exercise Can Improve Glucose Tolerance in Persons With Multiple Sclerosis: A Randomized Controlled Trial.


                                                                  
  

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Abstract

INTRODUCTION: The prevalence of impaired glucose tolerance (IGT) is higher in persons with multiple sclerosis (MS) compared to healthy controls, indicating metabolic deficits that may increase comorbidity. In other populations, IGT can, at least partly, be reversed by intense physical exercise, but this is never investigated before in MS.
AIM: To investigate the effect of high intensity aerobic and resistance training on glucose tolerance and skeletal muscle GLUT4 content in MS.
METHODS: Thirty-four persons with MS (aged 45 ± 3 years, EDSS 2.5 ± 1.07) were randomized into three groups, including a (1) sedentary control group (SED, n = 11), (2) 12-week high intensity interval plus resistance training group (HITR, n = 12), or (3) 12-week high intensity continuous aerobic training plus resistance training group (HCTR, n = 11). Before and after 12 weeks, glucose tolerance and skeletal muscle GLUT4 content were determined by an oral glucose tolerance test and analysis of a m.vastus lateralis biopsy, respectively.
RESULTS: There were no significant changes for subjects of SED. From pre- to post-intervention, total area under the glucose curve (tAUC) decreased significantly in both HITR (-6.9 ± 6.2%) and HCTR (-11.0 ± 7.7%) (P < 0.05). Insulin tAUC decreased (-12.3 ± 14.7%) within HCTR and muscle GLUT4 content increased (+6.6 ± 4.5%) in HITR.
CONCLUSION: Twelve weeks of high intensity aerobic exercise in combination with resistance training improved glucose tolerance in persons with MS.

See full report - here







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Assessment of vitamin D status - a changing landscape


                                                                  
  

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Abstract

In recent years it has been shown that vitamin D deficiency is associated with an increased incidence as well as the progression of a broad range of diseases including osteoporosis, rickets, cardiovascular disease, autoimmune disease, multiple sclerosis and cancer. Consequently, requests for the assessment of vitamin D status have increased dramatically. Despite significant progress in the analysis of vitamin D metabolites and an expansion of our pathophysiological knowledge of vitamin D, the assessment of vitamin D status remains a challenging and partially unresolved issue. Current guidelines from scientific bodies recommend the measurement of 25-hydroxy-vitamin D (25-OHD) in blood as the preferred test. However, growing evidence indicates significant limitations of this test, including analytical aspects and interpretation of results. In addition, the relationships between 25-OHD and various clinical indices, such as bone mineral density and fracture risk, are rather weak and not consistent across races. Recent studies have systematically investigated new markers of vitamin D status including the vitamin D metabolite ratio (VMR) (ratio between 25-OHD and 24,25-dihydroxy vitamin D), bioavailable 25-OHD [25-OHD not bound to vitamin D binding protein (DBP)], and free 25-OHD [circulating 25-OHD bound to neither DBP nor albumin (ALB)]. These parameters may potentially change how we will assess vitamin D status in the future. Although these new biomarkers have expanded our knowledge about vitamin D metabolism, a range of unresolved issues regarding their measurement and the interpretation of results prevent their use in daily practice.
Read complete article here





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High Intensity Training May Reverse the Fiber Type Specific Decline in Myogenic Stem Cells in MSers


                                                                  
  

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Abstract

Multiple sclerosis (MS) is associated with loss of skeletal muscle mass and function. The myogenic stem cells (satellite cells-SCs) are instrumental to accretion of myonuclei, but remain to be investigated in MS. The present study aimed to compare the SC and myonuclei content between MS patients (n = 23) and age matched healthy controls (HC, n = 18). Furthermore, the effects of 12 weeks of high intensity training on SC and myonuclei content were explored in MS. 





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Thursday, June 30, 2016

Roche's new multiple sclerosis drug set for early FDA approval


                                                                  
  

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by Ben Adams | Jun 28, 2016


Roche’s ($RHHBY) new multiple sclerosis drug, which targets a form of the disease that currently has no treatments, has been given a hurry-up status from the FDA as it looks to start earning on its blockbuster potential.

The regulator has granted Ocrevus (ocrelizumab) a priority review, speeding up the FDA’s process--which should see the drug gain a U.S. green light by 28 December, months ahead of the Swiss firm’s original goal date.

The med is seeking a license for both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS).

RMS already has a number of treatments on the market from Novartis ($NVS), Biogen ($BIIB), German Merck, Sanofi ($SNY), Teva ($TEVA) and others--but there are currently no drugs on the market for the progressive form of the disease, which makes up around 10-15% of all MS patients.

The drug, administered by intravenous infusion every 6 months, showed in clinical trials that it could better Merck's older injectable treatment Rebif in patients suffering from RMS. When compared with placebo, the drug also reduced the risk of disability progression by 24% in patients with the particularly debilitating PPMS.

READ More on Ocrevus (ocrelizumab






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EMA accepts for review Roche's Ocrevus MAA for relapsing multiple sclerosis & PPMS


                                                                  
  

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Basel, Switzerland
Wednesday, June 29, 2016, 12:00 Hrs  [IST]
Roche announced that the European Medicines Agency (EMA) has validated the company’s Marketing Authorisation Application (MAA) of Ocrevus (ocrelizumab) for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) in the European Union (EU).

Validation confirms that the submission is complete and signifies the MAA is under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The U.S. Food and Drug Administration (FDA) has also accepted for review Roche’s Biologics License Application (BLA) for Ocrevus for the treatment of RMS and PPMS, and has granted the application Priority Review Designation with a targeted action date of 28 December 2016. If approved by the EMA and FDA for both indications, Ocrevus would be the first and only treatment for both forms of multiple sclerosis (MS), which affect approximately 95 percent of people at diagnosis.

“Ocrevus is the first investigational medicine to significantly reduce disability progression in people with relapsing and primary progressive forms of MS,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are pleased by the acceptance of our marketing applications for Ocrevus, which we believe has the potential to help people living with either of these two forms of MS. We will continue to work closely with the EMA and FDA to bring this investigational medicine to people with MS as quickly as possible.”

The Ocrevus marketing applications are based on positive results from three phase III studies, which met primary and key secondary endpoints. Data from two identical studies (OPERA I and OPERA II) in people with RMS showed superior efficacy ofOcrevus in reducing annualised relapse rates and disability progression sustained for at least three and for at least six months compared with Rebif (interferon beta-1a). Data from the ORATORIO study in people with PPMS showed significant reductions in disability progression sustained for at least three and for at least six months, as well as in other measures of progressive disease compared with placebo. Overall safety (proportion of patients with adverse events and serious adverse events) of Ocrevus in the phase III studies was similar to interferon beta-1a in the RMS studies and to placebo in the PPMS study. The most common adverse events associated withOcrevus were infusion-related reactions and infections, which were mostly mild to moderate in severity.

Priority Review Designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment of a serious disease. In February 2016, the FDA granted Breakthrough Therapy Designation toOcrevus for the treatment of PPMS. Ocrevus is the first investigational medicine to receive Breakthrough Therapy designation in MS.

If the EMA’s CHMP adopts a positive opinion that is endorsed by the European Commission, Ocrevus will be granted a marketing authorization that will be valid in all 28 member states of the EU.

Roche has also recently submitted regulatory applications in Switzerland and Australia.

Ocrevus is the proprietary name submitted to global regulatory authorities for the investigational medicine ocrelizumab. Ocrevus is an investigational, humanised monoclonal antibody designed to selectively target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with MS. Based on preclinical studies, Ocrevus binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.

Read more on Ocrelizumab aka : Ocrevus



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New Trial of Hematopoietic Stem Cell Transplant for Aggressive Multiple Sclerosis


                                                                  
  

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A novel transplantation protocol was highly effective for suppressing inflammation in selected patients, but procedure-related morbidity remains a concern.
Hematopoietic stem cell transplant (HSCT) essentially resets the immune system by mobilizing stem cells, ablating the immune system, and reconstituting the immune system with autologous cells. HSCT is being tested as a treatment for multiple sclerosis (MS; NEJM JW Neurol Apr 2015 and JAMA 2015; 313:27). Now, researchers have conducted a phase II trial, enrolling patients from three centers who had poor prognostic features (e.g., expanded disability status scale [EDSS] ≥3.0 within 5 years after disease onset, ongoing disease activity after 1 year of standard MS therapy, or a cerebellar/pyramidal functional system score of ≥3). Median age was 34 years (range, 24–45) and median disease duration was 6 years (range, 1–11). Of 39 patients screened, 26 were enrolled, 24 underwent HSCT, 21 completed 3-year follow-up, and 13 were followed longer-term. MS activity-free survival at 3 years was 70%. The 30% with disease activity primarily had sustained disease worsening attributable to disease progression, not necessarily inflammatory activity. Before treatment, 24 patients had 167 relapses during a median 6 years. After HSCT, among 23 patients with 179 patient-years of follow-up, no clinical relapses occurred and no gadolinium-enhancing lesions were found; one person had 4 new T2 lesions 1 month posttransplant that were not present 5 months earlier. Improvement on the EDSS was observed in 40% and appeared to occur for several years after transplant.

Read more on Hematopoietic Stem Cell transplant






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Managing Bladder Dysfunction in Multiple Sclerosis


                                                                  
  

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Bladder dysfunction is a common problem in multiple sclerosis (MS), but it is still under-reported despite its significant effect on quality of life. Most estimates suggest that 75 to 80% of people with MS have bladder symptoms, but many don't talk about it.1-4 With preventive measures and treatment, bladder symptoms can be effectively managed.
"About three-quarters of the people that I see in clinical practice have bladder dysfunction,” agreed Megan Weigel, DNP, ARNP-C, MSCN, clinical MS nurse at Baptist Neurology in Jacksonville Beach, FL, and the incoming President of the International Organization of Multiple Sclerosis Nurses (IOMSN), "and I've read that as many as 90% can expect some symptoms within 10 years after the diagnosis.

Identifying Symptoms of Bladder Dysfunction


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Obesity and multiple sclerosis: Is there a causal relationship?


                                                                  
  

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Published: 





Mutiple sclerosis is an unpredictable condition of the central nervous system that ranges from mild to devastating; in people with the disease, communication between the brain and body is disrupted. However, the risk factors that cause the disease are poorly understood. Now, a new study investigates the link between obesity and multiple sclerosis.




The study, led by Dr. Brent Richards from the Jewish General Hospital in Quebec, Canada, is published in PLOS Medicine.
According to the National Institutes of Health (NIH), many experts believe multiple sclerosis (MS) is an autoimmune disease, whereby the body's immune system attacks its own tissues. With MS, the body attacks its own nerve-insulating myelin.
Most people encounter their first MS symptoms between 20-40 years of age, and initial symptoms include blurred or double vision, red-green distortion, or blindness in one eye.
The researchers from this latest study say that an elevated body mass index (BMI) has been shown to promote a "proinflammatory state," affecting the immune system.
READ MORE on Obesity and MS



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Bad gut bacteria linked to multiple sclerosis


                                                                  
  

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In the study published online in the journal Scientific Reports, the researchers said that MS patients do, in fact, have a distinct microbiome from their healthy peers.

June 28, 2016 By: IANS | New York

gut bacteria, good bacteria, bacteria, body bacteria, digestive bacteria, immune system, auto immune disease, sclerosis, multiple sclerosis

Every human carries trillions of bacteria in their gut (gut microbiome) and recent advances in research indicate that these tiny passengers play an important role in our overall health maintenance. (Source: Thinkstock Images)
Bad gut bacteria — or an insufficient amount of good bacteria — may have a direct link to multiple sclerosis, say researchers, including one of Indian-origin.
Multiple sclerosis is a chronic progressive auto-immune disease in which the immune system attacks the nervous tissue, potentially resulting in movement disorders.
Other typical symptoms of MS include physical and mental fatigue as well as faintness, depression and paresthesia such as pins and needles, itchiness and numbness.
“Every human carries trillions of bacteria in their gut (gut microbiome) and recent advances in research indicate that these tiny passengers play an important role in our overall health maintenance,” said Ashutosh Mangalam, Assistant Professor at the University of Iowa Carver College of Medicine in the US.
Since the bacteria are associated with contributing to good health, Mangalam and his colleagues wondered whether those with a chronic autoimmune disorder, such as multiple sclerosis, would then have a gut microbiome that is different than the microbiome found in healthy individuals.


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Summer-time is not always fun-time


                                                                  
  

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Stu's Views and MS News: 
For those of us with MS, summertime can often lead to being isolated as we need to remain indoors where the sun doesn't shine and where air-conditioning bills just seem to rise and rise... 



With summer upon us, many are feeling woozy, numb or quite tingly. fatigue might be at the worst levels you remember being. Cognition might be slightly defaulting as well and especially when you realize that you begin tasks but are not completing them. Maybe your memory is slightly off too.,, 

Does this mean you are relapsing? Maybe, and maybe not. -- 
Maybe you are simply experiencing Uhthoff's Syndrome:

(Uhthoff's phenomenon (also known as Uhthoff's syndrome, Uhthoff's sign, and Uhthoff's symptom) is the worsening of neurologic symptoms in multiple sclerosis (MS) and other neurological, demyelinating conditions when the body gets overheated from hot weather, exercise, fever, or saunas and hot tubs.)

These problems are often simply caused by the heat.. Try to remain in cooler environment and if you do not have air-conditioning, then you might want to go to the mall or a movie theatre where you can literally "chill-out" for a little while and then see how you feel.. 

If you have a cooling vest, now is the time to begin this new wardrobe design and if you do not have a vest, consider traveling-about with a small cooler with ice or ice packs inside and when you need to cool-down you will have the magic with you. Another good thing to do in the summer is drink cold water more-so that other things.

Of course, you could be relapsing as well and so, I will tell you all to speak with your MS Clinician before listening to my rants about remaining COOL (no, not like the Fonz) - but yes, your body and it's neurologic pathways do fair better in cooler temperatures.

So, now you have Stu's Views 


Disclaimer -- Not providing medical information. Just providing a little knowledge from one patient (me) to many



Ciao 







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