Plasmapheresis for neuroinflammatory disorders

Nowadays, therapeutic plasma exchange (PE) is the most common apheresis procedure. Plasma is separated from corpuscular blood constitutents and replaced with a substitution fluid. Thus, PE is a non-specific treatment modality. Its therapeutic effect is based on the removal of circulating, pathogenic immune factors, including autoantibodies. To date, PE is well established for several immune mediated neurological disorders. Whilst the first experience was acquired in acute life-threatening conditions, such as the treatment of Guillain–Barré syndrome or myasthenic crisis, therapeutic success was later achieved in other chronic autoimmune diseases; PE was applied successfully in chronic inflammatory demyelinating polyneuropathy, paraproteinaemic polyneuropathy, stiff-person syndrome and might also be tried in autoimmune diseases of paraneoplastic origin. From a novel aspect, PE was also established as an escalation therapy for steroid unresponsive relapses of multiple sclerosis, and thus has gained even more widespread attention. Humoral disease mechanisms dominate even more in neuromyelitis optica, as a subtype of MS, and usually respond to PE. Adding to its increasing application in clinical practice, the procedure is usually well tolerated. Possible adverse reactions of PE arise from the large-size vascular access site, the use of replacement fluids and the need for anticoagulation.

source: Clin. Exp. Neuroimmunology

Low Vitamin D Linked to Allergy Risk in Kids

Study Shows Greater Risk of Allergies for Kids and Adolescents Who Don’t Get Enough Vitamin D


child outdoors rubbing eyes

Feb. 25, 2011 — Children who don’t get enough vitamin D may be at increased risk of developing allergies, new research indicates.

Researchers in New York examined serum vitamin D levels in the blood of more than 3,100 children and adolescents and 3,400 adults.

No association was found between low vitamin D levels and allergies in adults, but the link was significant in children and adolescents.

Children and adolescents aged 1 to 21 with low vitamin D levels were at increased risk of having sensitivities to 11 of 17 allergens tested, including environmental and food allergies.

For example, children who had vitamin D deficiency, which was defined as less than 15 nanograms of vitamin D per milliliter of blood, were 2.4 times more likely to have a peanut allergy than kids with sufficient levels, or 30 nanograms of vitamin D per milliliter of blood.

Children with low vitamin D levels also had increased risk of allergic sensitization to shrimp, dogs, cockroaches, ragweed, oak, ryegrass, Bermuda grass, and thistle.

Avoiding Vitamin D Deficiency

The data came from the National Health and Nutrition Examination Survey 2005-2006 (NHANES), which is a program of studies aimed at assessing the health and nutritional status of adults and children in the U.S.

The study participants underwent blood tests measuring levels of Immunoglobulin E(IgE), a protein that is produced when the immune system responds to allergens.

Researchers say their findings don’t prove that insufficient vitamin D causes allergies in children and adolescents, but strongly suggests that young people should get adequate amounts of the vitamin.

“The latest dietary recommendations calling for children to take in 600 IU of vitamin D daily should keep them from becoming vitamin D deficient,” researcher Michal Melamed, MD, MHS, of the Albert Einstein College Medicine of Yeshiva University, says in a news release.

The study says vitamin D is thought to have anti-inflammatory effects in the body.

The researchers note that the prevalence of vitamin D deficiency is increasing in the U.S., and so is the prevalence of food allergies.

source: Journal of Allergy and Clinical Immunology.

Rescuing the Failing Heart by Targeted Gene Transfer

Congestive heart failure is a major cause of morbidity and mortality in the United States. Although progress in conventional treatments is making steady and incremental gains to decrease heart failure mortality, there is a critical need to explore new therapeutic approaches. Gene therapy was initially applied in the clinical setting for inherited monogenic disorders. It is now apparent that gene therapy has broader potential that also includes acquired polygenic diseases, such as congestive heart failure. Recent advances in understanding of the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, have placed heart failure within the reach of gene-based therapy. Furthermore, the recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum Ca2+ ATPase pump along with the start of more recent phase 1 trials are ushering in a new era of gene therapy for the treatment of heart failure.

source: JACC


Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women

Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men.
METHODS: In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878.
FINDINGS: During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27.8%) women in the intervention group and 189 (38.7%) in the control group had high-risk HPV infection (prevalence risk ratio=0.72, 95% CI 0.60-0.85, p=0.001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20.7 infections vs 26.9 infections per 100 person-years; incidence rate ratio=0.77, 0.63-0.93, p=0.008).
INTERPRETATION: Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important.
FUNDING: The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

source: lancet


Fidaxomicin versus vancomycin for Clostridium difficile infection

Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality. Patients generally have a response to oral vancomycin or metronidazole; however, the rate of recurrence is high. This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection.
METHODS: Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry. We randomly assigned patients to receive fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for 10 days. The primary end point was clinical cure (resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy). The secondary end points were recurrence of C. difficile infection (diarrhea and a positive result on a stool toxin test within 4 weeks after treatment) and global cure (i.e., cure with no recurrence).
RESULTS: A total of 629 patients were enrolled, of whom 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P=0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004). The lower rate of recurrence was seen in patients with non-North American Pulsed Field type 1 strains. The adverse-event profile was similar for the two therapies.
CONCLUSIONS: The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin. Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non-North American Pulsed Field type 1 strains.

source: NEJM

FDA Approves Edarbi for Hypertension

The FDA has approved the angiotensin II receptor blocker azilsartan medoxomil to treat hypertension in adults.

The drug, marketed as Edarbi, was shown to be more effective in lowering 24-hour blood pressure than valsartan or olmesartan. The agency says the drug will be available in two doses, 40 and 80 mg, with the lower dose intended for patients on high-dose diuretics.

A boxed warning cautions against use during pregnancy, because the drug can harm the fetus.

Source:FDA announcement


High Prostate-Specific Antigen “Velocity” Not a Reason for Biopsy

Patients may ask about a study that finds a high rate of change in prostate-specific antigen values — called PSA velocity — is not sufficient grounds for biopsy. The study appears in the Journal of the National Cancer Institute.

As part of a randomized trial of finasteride versus placebo in healthy men, researchers evaluated some 5500 men in the placebo arm. The men were aged 55 and older with initial PSA levels of 3.0 or less and normal digital rectal exams. They received yearly PSA tests and underwent biopsy after 7 years of placebo treatment.

The authors found that doing biopsy on the basis of a PSA velocity of greater than 0.35 ng/mL/yr — as some current guidelines suggest — would lead to only a “very small increase” in predictive accuracy and recommend against use of the measure in clinical guidelines. They argue that use of the velocity measure alone as an indication for biopsy would lead to large numbers of additional, unnecessary procedures.

Editorialists write that the results “remind us that the use of PSA as a screening tool still leaves much to be desired.”

source: JNCI study