Positioning of old and new biologicals and small molecules in the treatment of inflammatory bowel diseases

The past decade has brought substantial advances in the management of inflammatory bowel diseases(IBD). The introduction of tumor necrosis factor(TNF) antagonists, evidence for the value of combination therapy, the recog-nition of targeting lymphocyte trafficking and activation as a viable treatment, and the need for early treatment of high-risk patients are all fundamental concepts for current modern IBD treatment algorithms. In this article, authors review the existing data on approved biologicals and small molecules as well as provide insight on the current positioning of approved therapies. Patient stratification for the selection of specific therapies, therapeutic targets and patient monitoring will be discussed as well. The thera-peutic armamentarium for IBD is expanding as novel and more targeted therapies become available. In the absence of comparative trials, positioning these agents is becoming difficult. Emerging concepts for the future will include an emphasis on the development of algorithms which will facilitate a greater understanding of the positioning of novel biological drugs and small molecules in order to best tailor therapy to the patient. In the interim, anti-TNF therapy remains an important component of IBD therapy with the most real-life evidence and should be considered as first-line therapy in patients with complicated Crohn's disease and in acute-severe ulcerative colitis. The safety and efficacy of these ‘older' anti-TNF therapies can be optimized by adhering to therapeutic algorithms which combine clinical and objective markers of disease severityand response to therapy.     

Vitamin D Deficiency and Tuberculosis Progression

To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.     

Stroke in childhood: experience in Istanbul, Turkey

Our objective was to characterize the etiologic factors and outcome for stroke in children. We retrospectively reviewed the charts of patients between the ages of 40 days and 94 months (36.5 +/- 23.7 months) with stroke seen at Istanbul Medical Faculty, Department of Pediatrics between January 1995 and December 2003. We found 79 cases of stroke: 57 ischemic and 22 hemorrhagic strokes. Seventeen children had vitamin K deficiency dependent hemorrhage. In 14 children stroke occurred as a complication of cardiac disease, 7 had moyamoya disease, 3 had protein C deficiency, 2 had thalassemia, 2 had hyperhomocysteinemia (methylene tetrahydrofolate reductase gene mutation), 2 were heterozygote for factor V Leiden, 3 had Down's syndrome, 1 was diagnosed with antiphospholipid syndrome, 1 had glycogen storage disease, and in 28 children no underlying cause could be found. Multiple risk factors were found in 4 children. The outcome in all 79 stroke patients was as follows: asymptomatic 60%; symptomatic epilepsy or persistent neurologic deficit 37%; death 3%; and recurrent stroke 5%. Thus, an underlying cause for stroke was identified in 65% of the children in the study group; 40% of the children either died or suffered motor and/or cognitive sequelae.     

Evaluation of a Thin-film Peripheral Nerve Cuff Electrode

Abstract

This is a study of the reaction of large nerves to implantation using a flexible, thin-film cuff electrode. Cuff electrodes were implanted on the sciatic nerve of three cats. An implantation period of six weeks allowed sufficient time for any injury responses in the nerve and connective tissue sheath around the cuff to develop. The electrode came off the nerve in one of the cats. In the remaining two cats, gross observation following explantation of the electrodes revealed encapsulation of the cuffs without swelling of nerve tissue. Histological evaluation did not demonstrate nerve injury. The nerve cuff electrodes, which are comprised of titanium and iridium coatings on a fluorocarbon polymer substrate, appeared unaffected by the implantation, and connective tissue encapsulation did not adhere to either the polymer substrate or metallization. Evaluation of the electrodes using activated iridium oxide charge injection sites in more extended studies is now being undertaken. (J Spinal Cord Med; 18:28–32)     

Do Direct Current Electric Fields Enhance Micturition in the Spinal Cat?

ABSTRACT

Changes in micturition behavior and motoneuron ultrastructure were studied in spinal cats to determine the effects of direct current (DC) electric field treatment. Adult cats received a complete injury at T8. A treatment group with an implanted 15 pA DC source and electrodes positioned near the lesion site was compared with non-treatment groups that were either operated or unoperated. Both bladder emptying with Crede and the withdrawal reflex were improved in the treatment group compared with the non-treatment group. Urodynamic procedures showed that high urethral resistance and pelvic floor activity following spinal injury was partially reduced in the stimulated cat, indicating inhibition of the urethral sphincter. The ultrastructural analysis of Onuf’s nucleus suggested a similar synaptic input in all three groups. In conclusion, possible activation of inhibitory processes and/or neural plasticity best explain the early improvement of bladder function seen following electrical stimulation. (J Spinal Cord Med 19:225–233)     

Cluster of Middle East Respiratory Syndrome Coronavirus Infections in Iran, 2014

During January 2013–August 2014, a total of 1,800 patients in Iran who had respiratory illness were tested for Middle East respiratory syndrome coronavirus. A cluster of 5 cases occurred in Kerman Province during May–July 2014, but virus transmission routes for some infections were unclear.     

Helicobacter pylori infection in epileptic patients.

It is well known that there might be an epidemiological association between Helicobacter pylori infection and extraintestinal diseases. This study aimed at determining H. pylori infection in epileptic patients. Forty-seven cryptogenic epileptic patients (Group 1) and 35 healthy people (Group 2) participated in this study. Presence of H. pylori infection was examined by H. pylori stool antigen (HpSA), H. pylori IgG, and IgM. HpSA was detected in 21 participants (44.6%) in Group 1 and in 3 participants (8.5%) in Group 2. H. pylori IgM was positive in 27 participants (57.4%) in Group 1 and in 8 participants (22.8%) in Group 2. H. pylori IgG was positive in 37 participants (78.7%) in Group 1 and in 13 participants (38%) in Group 2. The difference of rates of HpSA, H. pylori IgM and IgG in Groups 1 and 2 were found statistically significant (chi2=4.18, p=0.04; chi2=9.18, p=0.0017; chi2=14.58, p<0.001, respectively). We also compared presence of H. pylori infection between the epileptic patients with poor and good prognosis; HpSA positivity was detected in 15 (62.5%) of 24 and 6 (26%) of 23, respectively, and the differences were statistically significant (chi2=6.30, p=0.012). H. pylori IgM positivity was detected in 16 (66%) of 24 patients with poor prognosis and 11 (47.8%) of 23 patients with good prognosis (p>0.05). H. pylori IgG positivity was detected in 18 (75%) of 24 patients with poor prognosis and 19 (82.6%) of 23 patients with good prognosis. The differences of H. pylori IgM and IgG positivity rates in epileptic patients with poor and good prognosis were not found statistically significant (p>0.05). These results suggest a probable association between the acute H. pylori infection and epilepsy, especially with poor prognosis.