TNF-alpha blockers in inflammatory bowel diseases: practical consensus recommendations and a user's guide.

More than seventy years after their initial characterisation, the aetiology of inflammatory bowel diseases remains elusive. A recent review evaluating the incidence trends of the last 25 years concluded that an increasing incidence has been observed almost worldwide. A north-south gradient is still found in Europe. Genetic associations are variably reproduced worldwide and indicate a strong impact of environmental factors. Tumour necrosis factor alpha (TNF-alpha) has been shown to play a critical role in the pathogenesis of inflammatory bowel disease (IBD). TNF-alpha blockers are biological agents that specifically target this key cytokine in the inflammatory process and have become a mainstay in the therapy of inflammatory bowel diseases. This paper reviews the necessary investigations before using such agents, the use of such agents in pregnancy and lactation, the role of co-immunosuppression, how to monitor efficacy and safety, dose-adaptation, and the decision as to when to switch to another TNF-alpha blocker. Finally it gives recommendations for special situations. Currently there are three TNF-alpha blockers available for clinical use in IBD in Switzerland: infliximab (Remicade), adalimumab (Humira) and certolizumab pegol (Cimzia). Infliximab is a chimeric monoclonal antibody composed of a human IgG1 constant region and a murine variable region and is administered intravenously. Adalimumab is a humanised monoclonal antibody, with both human IgG1 constant and variable regions. Certolizumab pegol is a pegylated, humanised monoclonal anti-TNF fragment antigen binding fragment. Both adalimumab and certolizumab pegol are administered by subcutaneous injection. The efficacy and safety of TNF-alpha blockers in Crohn's disease has been reviewed. The authors conclude that the three above-mentioned agents are effective in luminal Crohn's disease. In fistulizing Crohn's disease, TNF-alpha blockers other than infliximab require additional investigation.

A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25 ml). Either L. reuteri or L. fermentum was daily administered orally (5 x 10(8) colony-forming units suspended in 0.5 ml skimmed milk) to each group of rats (n 10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P<0.05). L. fermentum significantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFalpha levels (P<0.01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved with L.fermentum administration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased when L. fermentum was given. In conclusion, L. fermentum can exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective than L. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

Acidosis D-Láctica secundaria a síndrome de intestino corto.

The short bowel syndrome appears for the reduction of intestinal absorptive surface due to functional or anatomical loss of part of the small bowel. We present the case of a 35-year-old woman with severe short bowel syndrome secondary to acute intestinal ischemia in adults, who presented at 5 years of evolution episodes of dizziness with gait instability and loss of strength in hands. The diagnosis was D-lactic acidosis. D-lactic acidosis is a rare complication, but important for their symptoms, of this syndrome. It is due to a change in intestinal flora secondary to an overgrowth of lactic acid bacteria that produce D-lactate. D-lactic acidosis should be looked for in cases of metabolic acidosis in which the identity of acidosis is not apparent, neurological manifestations without focality and the patient has short bowel syndrome or patients who have had jejunoileal bypass surgery. Appropriate treatment usually results in resolution of neurologic symptoms and prevents or reduces further recurrences.

Home parenteral nutrition in children: procedures, experiences and reflections.

This document summarizes the issues raised in a think-tank meeting held by professionals with expertise in pediatric Home Parenteral Nutrition. This nutritional technology enables patients to return home to their family and social environment, improves their quality of life and decreases health-care costs; however, it is complex and requires an experienced nutritional support team. Patient selection is normally made according to their underlying disease, the estimated duration of support and family and social characteristics. The patient''s family must agree to take on caregiver's responsibilities and should be able to perform treatment safely and effectively after receiving proper training from the nutritional support team. Close monitoring must be carried out to ensure tolerance and effectiveness of nutritional support, thereby avoiding complications. This nutritional treatment achieves, in most cases, recovery and intestinal adaptation in varying periods of time. In certain diseases, and when home parenteral nutrition becomes complicated, intestinal transplant may be recommendable, so referral to rehabilitation units and Intestinal Transplantation should be made early on.

Use of unmodified starches and partial removal of serum to improve Granada medium stability

The use of 1% unmodified rice starch and 1% horse serum instead of 2% soluble starch and 5% serum in Granada medium is described. These components result in a medium of increased stability, preventing spoilage after a few days of storage at room temperature

Specimen storage in transport medium and detection of group B streptococci by culture

Recovery of group B streptococci (GBS) was assessed in 1,204 vaginorectal swabs stored in Amies transport medium at 4 or 21°C for 1 to 4 days either by direct inoculation onto Granada agar (GA) or by culture in blood agar (BA) and GA after a selective broth enrichment (SBE) step. Following storage at 4°C, GBS detection in GA was not affected after 72 h by either direct inoculation or SBE; however, GBS were not detected after SBE in the BA subculture in some samples after 48 h of storage and in GA after 96 h. After storage at 21°C, loss of GBS-positive results was significant after 48 h by direct inoculation in GA and after 96 h by SBE and BA subculture; some GBS-positive samples were not detected after 24 h of storage followed by SBE and BA subculture or after 48 h of storage followed by SBE and GA subculture. Storage of swabs in transport medium, even at 4°C, produced after 24 h an underestimation of the intensity of GBS colonization in most specimens. These data indicate that viability of GBS is not fully preserved by storage of vaginorectal swabs in Amies transport medium, mainly if they are not stored under refrigeration

Transmission blocking vaccines to control insect-borne diseases: a review

Insect-borne diseases are responsible for severe mortality and morbidity worldwide. As control of insect vector populations relies primarily on the use of insecticides, the emergence of insecticide resistance as well to unintended consequences of insecticide use pose significant challenges to their continued application. Novel approaches to reduce pathogen transmission by disease vectors are been attempted, including transmission-blocking vaccines (TBVs) thought to be a feasible strategy to reduce pathogen burden in endemic areas. TBVs aim at preventing the transmission of pathogens from infected to uninfected vertebrate host by targeting molecule(s) expressed on the surface of pathogens during their developmental phase within the insect vector or by targeting molecules expressed by the vectors. For pathogen-based molecules, the majority of the TBV candidates selected as well as most of the data available regarding the effectiveness of this approach come from studies using malaria parasites. However, TBV candidates also have been identified from midgut tissues of mosquitoes and sand flies. In spite of the successes achieved in the potential application of TBVs against insect-borne diseases, many significant barriers remain. In this review, many of the TBV strategies against insect-borne pathogens and their respective ramification with regards to the immune response of the vertebrate host are discussed.

High Prevalence of Systemic Autoimmune Diseases in Patients with Meniere's Disease

BACKGROUND. Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS. We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS. Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.

The Estrada Real project and endemic diseases: the case of schistosomiasis, geoprocessing and tourism

Geographical Information System (GIS) is a tool that has recently been applied to better understand spatial disease distributions. Using meteorological, social, sanitation, mollusc distribution data and remote sensing variables, this study aimed to further develop the GIS technology by creating a model for the spatial distribution of schistosomiasis and to apply this model to an area with rural tourism in the Brazilian state of Minas Gerais (MG). The Estrada Real, covering about 1,400 km, is the largest and most important Brazilian tourism project, involving 163 cities in MG with different schistosomiasis prevalence rates. The model with three variables showed a R² = 0.34, with a standard deviation of risk estimated adequate for public health needs. The main variables selected for modelling were summer vegetation, summer minimal temperature and winter minimal temperature. The results confirmed the importance of Remote Sensing data and the valuable contribution of GIS in identifying priority areas for intervention in tourism regions which are endemic to schistosomiasis.

Reseccion intestinal masiva. Proceso de adaptacion nutricional

INTRODUCTION Massive small bowel resection (MSBR) with a remnant jejunum shorter than 60 cm produces severe water, electrolytes, vitamins and protein-caloric depletion. While waiting for a viable intestinal transplantation, most of MSBR patients depend on total parenteral nutrition (TPN). CLINICAL CASE 32 years old male, with MSBR due to sectioning trauma of the superior mesenteric artery root. First surgical intervention: jejunostomy with small bowel, right colon, and spleen resection. Six months later: jejunocolic anastomosis with 12-cm long jejunum remnant and prophylactic cholecystectomy. NUTRITIONAL INTERVENTION: 1st phase. Hemodynamic stabilization and enteral stimulation (6 months): TPN + enteral nutrition with elemental formula + oral glucohydroelectrolitic solution (OGHS) + 15 g/d of oral glutamine + omeprazol. Clinical course indicators: biochemistry, I/L balance. 2a phase. Digestive adaptation with colonic integration (8 months): replacement of TPN by part-time peripheral PN. Progressive cooked diet complemented with pancreatic poly-enzyme preparation, omeprazol, OGHS, glutamine, elemental formula. Clinical course indicators: biochemistry, diuresis, weight and feces. 3a phase. Auto-sufficiency without parenteral dependence: fragmented free oral diet supplemented with pancreatic poly-enzyme preparation, mineralized beverages, enteral formula supplement, Ca and Mg oral supplements, oral multivitamin and mineral preparation, monthly IM vitamin B12. Current situation actual (52 months): slight ponderal gain, diuresis > liter/day, 2-3 normal feces, no clinical signs of any deficiency and normal blood levels of micronutrients. CONCLUSION It may be possible to withdraw from PN in MSBR considering, as in this case, favorable age and etiology and early implementation of an appropriate protocol of remnant adaptation.

Resección intestinal masiva: Proceso de adaptación intestinal.

Carta al Director de J. M. Moreno Villares, sobre el artículo: Leyva Martínez S, Fernández Lloret S, Martín Ruiz JL. Resección intestinal masiva. Proceso de adaptación intestinal. Nutr Hosp 2007; 22:616-20; y réplica de los autores (Leyva Martínez S).

Pregnancy and reproduction in autoimmune rheumatic diseases.

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

An Open-Label, Noncomparative, Multicenter Study to Evaluate Efficacy and Safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence

Fecal incontinence (FI) is the involuntary loss of rectal contents through the anal canal. Reports of its prevalence vary from 1-21%. Studies, have demonstrated a positive effect on FI symptoms with injectable bulking agents. This study evaluated the safety and efficacy of NASHA/Dx gel in the treatment of FI. One hundred fifteen eligible patients suffering from FI received 4 injections of 1 mL NASHA/Dx gel. Primary efficacy was based on data from 86 patients that completed the study. This study demonstrated a ≥50% reduction from baseline in the number of FI episodes in 57.1% of patients at 6 months, and 64.0% at 12 months. Significant improvements (P < .001) were also noted in total number of both solid and loose FI episodes, FI free days, CCFIS, and FIQL scores in all 4 domains. The majority of the treatment related AEs (94.9%) were mild or moderate intensity, and (98.7%) of AEs resolved spontaneously, or following treatment, without sequelae. Results of this study indicate NASHA/Dx gel was efficacious in the treatment of FI. Treatment effect was significant both in reduction of number of FI episodes and disease specific quality of life at 6 months and lasted up to 12 months after treatment.