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.

Assessment of quality of life of patients under phototherapy for dermatological diseases

The skin and appendages is one of the first things in which people repair their social relationships as an alteration of these can influence the image and in multiple aspects of the subject’s life. Psoriasis is a chronic, relapsing skin disease that produces a marked reduction in the quality of life. Phototherapy, especially in form of narrow-band UVB is an alternative treatment of choice in plaque psoriasis and psoriasis of moderate extent. Also, regarding the impact of such treatment on quality of life of patients with psoriasis, there are few studies analyzing this effect.

An antibody-based ELISA for quantification of Ani s 1, a major allergen from Anisakis simplex.

Anisakis simplex is a nematode parasite that can infect humans who have eaten raw or undercooked seafood. Larvae invading the gastrointestinal mucosa excrete/secrete proteins that are implicated in the pathogenesis of anisakiasis and can induce IgE-mediated symptoms. Since Ani s 1 is a potent secreted allergen with important clinical relevance, its measurement could assess the quality of allergenic products used in diagnosis/immunotherapy of Anisakis allergy and track the presence of A. simplex parasites in fish foodstuffs. An antibody-based ELISA for quantification of Ani s 1 has been developed based on monoclonal antibody 4F2 as capture antibody and biotin-labelled polyclonal antibodies against Ani s 1 as detection reagent. The dose-response standard curves, obtained with natural and recombinant antigens, ranged from 4 to 2000 ng/ml and were identical and parallel to that of the A. simplex extract. The linear portion of the dose-response curve with nAni s 1 was between 15 and 250 ng/ml with inter-assay and intra-assays coefficients of variation less than 20% and 10%, respectively. The assay was specific since there was no cross-reaction with other extracts (except Ascaris extracts) and was highly sensitive (detection limit of 1·8 ng/ml), being able to detect Ani s 1 in fish extracts from codfish and monkfish.

Diarrea crónica refractaria y malabsorción secundaria a hipogammaglobulinemia común variable, infestación crónica por giardia lambila y gastrectomía total por adenocarcinoma gástrico: un manejo nutricional complejo

Gastric cancer is a frequent cause of cancer-related mortality in the world. Surgery is the only potentially curative therapy, although the adverse effects of surgery are common and considerable. Common variable immunodeficiency is in many cases cause of gastrointestinal system problems such as chronic diarrhea caused by infestation with giardia lamblia, nodular lymphoid hiperplasia ad loss of villi leading frequently to malapsortion and malnutrition. Nutritional deficiencies due to malapsorption (postgastrectomy and secondary to loss of villi, giardiasis and common variable inmunodeficiency) are common. We present the case of a patient with gastric cancer who underwent a gastrectomy with common variable hipogammaglobulinemia and chronic infestation by giardia lamblia, with serious diarrhea resistant to treatment and malabsorption.

Dietoterapia en paciente con linfangiectasia intestinal primaria y ascitis quilosa de repetición.

OBJECTIVES Primary intestinal lymphangiectasia is a lymphatic system's disorder, where lymphatic drainage is blockaged. Clinically it produces malabsorption, protein-losing enteropathy, hypogammaglobulin in blood, and several degrees of malnutrition. Its treatment is not easy and includes dietetic-therapy and drugs. MATERIAL AND METHOD A 35-year-old-woman case report is exposed. She has recurrent chylosa ascites, requiring several admissions and evacuatory paracentesis. After food-fat was replaced by medium-chain triacyl-glicerol-enriched diet, a clinical, analytical and anthropometric improvement was demonstrated. CONCLUSIONS The major way of treatment in intestinal lymphangiectasia in this case is the employement of specific-diet and adaptaded-basic-food. It's difficult and high collaboration of the patient is required, being necessary medical revisions during the whole life, due to the not well known evolution of this long-standing disease.

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).

Is the RET proto-oncogene involved in the pathogenesis of intestinal neuronal dysplasia type B?

Hirschsprung disease (HSCR) is defined by the absence of intramural ganglia of Meissner and Auerbach along variable lengths of the gastrointestinal tract. Intestinal neuronal dysplasia (IND) type B is characterized by the malformation of the parasympathetic submucous plexus of the gut. A connection appears to exist between these two enteric nervous system abnormalities. Due to the major role played by the RET proto-oncogene in HSCR, we sought to determine whether this gene was also related to INDB. dHPLC techniques were employed to screen the RET coding region in 23 patients presenting with INDB and 30 patients with a combined HSCR+INDB phenotype. In addition, eight RET single nucleotide polymorphisms (SNPs) were strategically selected and genotyped by TaqMan technology. The distribution of SNPs and haplotypes was compared among the different groups of patients (INDB, HSCR+INDB, HSCR) and the controls. We found several RET mutations in our patients and some differences in the distribution of the RET SNPs among the groups of study. Our results suggest an involvement of RET in the pathogenesis of intestinal INDB, although by different molecular mechanisms than those leading to HSCR. Further investigation is warranted to elucidate these precise mechanisms and to clarify the genetic nature of INDB.

Tratamiento nutricional del fallo intestinal y potenciales mecanismos de estimulación.

Severe forms of intestinal failure represent one of the most complex pathologies to manage, in both children and adults. In adults, the most common causes are chronic intestinal pseudo-obstruction and severe short bowel syndrome following large intestinal resections, particularly due to massive mesenteric ischemic, within the context of cardiopathies occurring with atrial fibrillation. The essential management after stabilizing the patient consists in nutritional support, either by parenteral or enteral routes, with tolerance to oral diet being the final goal of intestinal adaptation in these pathologies. Surgery may be indicated in some cases to increase the absorptive surface area. Parenteral nutrition is an essential support measure that sometimes has to be maintained for long time, even forever, except for technique-related complications or unfavorable clinical course that would lead to extreme surgical alternatives such as intestinal transplantation. Hormonal therapy with trophism-stimulating factors opens new alternatives that are already being tried in humans.

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case–control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.

Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Objective. To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting. The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls. Main outcome measures. Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. Results. 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

Expression of PROKR1 and PROKR2 in Human Enteric Neural Precursor Cells and Identification of Sequence Variants Suggest a Role in HSCR

Background. The enteric nervous system (ENS) is entirely derived from neural crest and its normal development is regulated by specific molecular pathways. Failure in complete ENS formation results in aganglionic gut conditions such as Hirschsprung's disease (HSCR). Recently, PROKR1 expression has been demonstrated in mouse enteric neural crest derived cells and Prok-1 was shown to work coordinately with GDNF in the development of the ENS. Principal Findings. In the present report, ENS progenitors were isolated and characterized from the ganglionic gut from children diagnosed with and without HSCR, and the expression of prokineticin receptors was examined. Immunocytochemical analysis of neurosphere-forming cells demonstrated that both PROKR1 and PROKR2 were present in human enteric neural crest cells. In addition, we also performed a mutational analysis of PROKR1, PROKR2, PROK1 and PROK2 genes in a cohort of HSCR patients, evaluating them for the first time as susceptibility genes for the disease. Several missense variants were detected, most of them affecting highly conserved amino acid residues of the protein and located in functional domains of both receptors, which suggests a possible deleterious effect in their biological function. Conclusions. Our results suggest that not only PROKR1, but also PROKR2 might mediate a complementary signalling to the RET/GFRα1/GDNF pathway supporting proliferation/survival and differentiation of precursor cells during ENS development. These findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in combination with RET or GDNF mutations, provide the first evidence to consider them as susceptibility genes for HSCR.

The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells

The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR)as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNalpha treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner,inducing phosphorylation of the protein synthesis translation initiation factor eIF-2alpha and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNalpha combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug.

Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia

Introduction: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy inceliac patients. Methods: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in μmol/L, and so are other clinical and analytical data. Results: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively) than in controls (28.9 μmol/l, 56.2 μmol/l, 563.7 μmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 μmol/l vs. 19.7 μmol/l, p < 0.05), not happening so with rest of amminoacids. Summary: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline in cases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline.

CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

Background: A functional polymorphism located at 21 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves’ disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves’ disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn’s disease (CD) lesions. Methodology: Genotyping of rs1883832C.T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings: The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p= 0.025; OR (95% CI)= 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p= 0.002; OR (95% CI)= 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p= 0.5; OR (95% CI)= 1.04 (0.93–1.17)]. Conclusion: The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions