Long term persistence and risk factors for anorectal symptoms following low anterior resection for rectal cancer.

BACKGROUND: Rectal cancer is commonly treated by chemoradiation therapy, followed by the low anterior resection anal sphincter-preserving surgery, with a temporary protecting ileostomy. After reversal of the stoma a condition known as low anterior resection syndrome (LARS) can occur characterized by a combination of symptoms such as urgent bowel movements, lack of control over bowel movements, and difficulty fully emptying the bowels. These symptoms have a significant negative impact on the quality of life for individuals who have survived the cancer. Currently, there is limited available data regarding the presence, risk factors, and effects of treatment for these symptoms during long-term follow-up. AIMS: To evaluate long term outcomes of low anterior resection surgery and its correlation to baseline anorectal manometry (ARM) parameters and physiotherapy with anorectal biofeedback (BF) treatment. METHODS: One hundred fifteen patients (74 males, age 63 ± 11) who underwent low anterior resection surgery for rectal cancer were included in the study. Following surgery, patients were managed by surgical and oncologic team, with more symptomatic LARS patients referred for further evaluation and treatment by gastroenterologists. At follow up, patients were contacted and offered participation in a long term follow up by answering symptom severity and quality of life (QOL) questionnaires. RESULTS: 80 (70%) patients agreed to participate in the long term follow up study (median 4 years from stoma reversal, range 1-8). Mean time from surgery to stoma closure was 6 ± 4 months. At long term follow up, mean LARS score was 30 (SD 11), with 55 (69%) patients classified as major LARS (score > 30). Presence of major LARS was associated with longer time from surgery to stoma reversal (6.8 vs. 4.8 months; p = 0.03) and with adjuvant chemotherapy (38% vs. 8%; p = 0.01). Patients initially referred for ARM and BF were more likely to suffer from major LARS at long term follow up (64% vs. 16%, p < 0.001). In the subgroup of patients who underwent perioperative ARM (n = 36), higher maximal squeeze pressure, higher maximal incremental squeeze pressure and higher rectal pressure on push were all associated with better long-term outcomes of QOL parameters (p < 0.05 for all). 21(54%) of patients referred to ARM were treated with BF, but long term outcomes for these patients were not different from those who did not perform BF. CONCLUSIONS: A significant number of patients continue to experience severe symptoms and a decline in their quality of life even 4 years after undergoing low anterior resection surgery. Prolonged time until stoma reversal and adjuvant chemotherapy emerged as the primary risk factors for a negative prognosis. It is important to note that referring patients for anorectal physiology testing alone tended to predict poorer long-term outcomes, indicating the presence of selection bias. However, certain measurable manometric parameters could potentially aid in identifying patients who are at a higher risk of experiencing unfavorable functional outcomes. There is a critical need to enhance current treatment options for this patient group.

Local T1-T2 distribution measurements in porous media.

A novel slice-selective T1-T2 measurement is proposed to measure spatially resolved T1-T2 distributions. An adiabatic inversion pulse is employed for slice-selection. The slice-selective pulse is able to select a quasi-rectangular slice, on the order of 1 mm, at an arbitrary position within the sample.The method does not employ conventional selective excitation in which selective excitation is often accomplished by rotation of the longitudinal magnetization in the slice of interest into the transverse plane, but rather a subtraction based on CPMG data acquired with and without adiabatic inversion slice selection. T1 weighting is introduced during recovery from the inversion associated with slice selection. The local T1-T2 distributions measured are of similar quality to bulk T1-T2 measurements. The new method can be employed to characterize oil-water mixtures and other fluids in porous media. The method is beneficial when a coarse spatial distribution of the components is of interest.

Whole exome sequencing of a consanguineous family identifies the possible modifying effect of a globally rare AK5 allelic variant in celiac disease development among Saudi patients.

Celiac disease (CD), a multi-factorial auto-inflammatory disease of the small intestine, is known to occur in both sporadic and familial forms. Together HLA and Non-HLA genes can explain up to 50% of CD's heritability. In order to discover the missing heritability due to rare variants, we have exome sequenced a consanguineous Saudi family presenting CD in an autosomal recessive (AR) pattern. We have identified a rare homozygous insertion c.1683_1684insATT, in the conserved coding region of AK5 gene that showed classical AR model segregation in this family. Sequence validation of 200 chromosomes each of sporadic CD cases and controls, revealed that this extremely rare (EXac MAF 0.000008) mutation is highly penetrant among general Saudi populations (MAF is 0.62). Genotype and allelic distribution analysis have indicated that this AK5 (c.1683_1684insATT) mutation is negatively selected among patient groups and positively selected in the control group, in whom it may modify the risk against CD development [p<0.002]. Our observation gains additional support from computational analysis which predicted that Iso561 insertion shifts the existing H-bonds between 400th and 556th amino acid residues lying near the functional domain of adenylate kinase. This shuffling of amino acids and their H-bond interactions is likely to disturb the secondary structure orientation of the polypeptide and induces the gain-of-function in nucleoside phosphate kinase activity of AK5, which may eventually down-regulates the reactivity potential of CD4+ T-cells against gluten antigens. Our study underlines the need to have population-specific genome databases to avoid false leads and to identify true candidate causal genes for the familial form of celiac disease.

Epidemiology and medical cost of hospitalization due to rotavirus gastroenteritis among children under 5 years of age in the central-east of Tunisia.

Data on the economic burden of rotavirus infection in Tunisia are needed to inform the decision to include rotavirus in routine childhood immunizations. This study aimed to describe the epidemiological profile of rotavirus disease in central-east Tunisia and to estimate its hospital cost. In the first stage - the prospective collection of epidemiological data - we enrolled all patients < 5 years old who were hospitalized for acute diarrhoea at 5 university paediatric departments in central-east Tunisia during the period 2009-2011. Rotavirus was responsible for 65 (23.3%) of the 279 cases enrolled. In the second stage, cost data were collected retrospectively using an activity-based costing method from the medical records of the children who were positively diagnosed with rotavirus. The average cost of care per child was TD 433 (SD 134). This is a significant economic burden in Tunisia, where a safe and effective vaccine is available but not yet introduced to the immunization schedule.

A novel association between IL1-Ra (receptor antagonist) gene polymorphism and T1DM in Al-Madina Al-Mounawra.

OBJECTIVE: The Interleukin-1 receptor antagonist (IL1-Ra) is initiated to terminate the acute pro-inflammatory event and prevent chronic inflammation from damaging healthy cells. We aim to draw the attention of IL1-Ra (VNTR) gene polymorphism and determine whether IL1-Ra confer susceptibility to type 1 diabetes mellitus (T1DM) and evaluate the genotype and allele distribution of IL1-Ra gene in a Saudi population. PATIENTS AND METHODS: Case control study included (100) T1DM Saudi children, plus 102 healthy unrelated individuals as control group. They were evaluated for variable number of tandem repeat (VNTR) of IL1-Ra gene polymorphism. Polymerase chain reaction amplification of VNTR of 86bp in intron 2 of IL1-Ra was performed. RESULTS: A1A1 and A1A2 genotypes with alleles A1 and A2 frequency were the most common both in cases and controls (healthy population); prevalence (28%, 56% & 57.8%, 39.2% respectively) and (58%, 38% and 77.5%, 22.5% respectively). In addition IL1-Ra gene polymorphism had higher risk significantly different between diabetic children and controls. (A1/A2) genotype had higher frequency statistically significant in DM patients than controls [56% vs. 39.2%, p < 0.02] and had twice time risk [OR = 1.97, 95% CI = 1.1-3.4, p < 0.02]. With further stratification, there was strong association between diabetic patients carriage IL1-Ra (A2) allele and controls [38% vs. 22.5%, p = 0.001] which had higher risk [OR = 2.11, 95% CI = 1.4-3.2, p = 0.001] for susceptibility of diabetes. CONCLUSIONS: This study emphasizes a positive association between IL1-Ra (VNTR) polymorphism and DM among Saudi children. This may suggest that (A2) allele may play important role in disease susceptibility.

[A rare cause of recurrent meningitis in children: cochleovestibular dysplasia]. / Une cause rare de méningite récurrente chez l'enfant: la dysplasie cochléovestibulaire.

Recurrent bacterial meningitis is an uncommon disease of childhood. It occurs most often in children who have an underlying predisposing disorder that can result from anatomic fistula or immunodeficiency. Cochleovestibular dysplasia is a rare malformation of the inner ear that is often associated with translabyrinthine cerebrospinal fistula and then can cause recurrent bacterial meningitis. We report an unusual case of recurrent meningitis revealing cochleovestibular dysplasia in a 9-year-old child. The malformation was confirmed by imaging and the child had surgery. The outcome was favourable with no recurrence of meningitis during the 3 years after the operation.

Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients.

Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22-5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05-2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17-0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD.

Recovery of Hafnia alvei from diseased brown trout, Salmo trutta L., and healthy noble crayfish, Astacus astacus (L.), in Bulgaria.

Hafnia alvei was isolated in Bulgaria from healthy noble crayfish, Astacus astacus (L.), and then from farmed diseased brown trout, Salmo trutta L., with signs of haemorrhagic septicaemia. The isolates were identified initially with conventional phenotyping and commercial Merlin Micronaut and API 20E rapid identification systems, followed by sequencing of the 16S rRNA gene. Hafnia alvei Bt1, Bt2 and Aa4 were of low virulence to rainbow trout and brown trout, although cytotoxicity was demonstrated by Bt1 and Bt2, but not by Aa4.

[Pediatric Crohn's disease in Tunisia]. / La maladie de Crohn de l'enfant en Tunisie.

UNLABELLED: Crohn's disease occur mainly in adults. However, pediatric onset forms are not rare and have many characteristics. AIM: to study clinical, diagnostic, therapeutic and evolutive characteristics of crohn's disease in tunisian children. METHODS: Retrospective multicenter study conducted in 10 pediatric departments on a period of 10 years (2000-2008) RESULTS : 43 children were included. The sex-ratio was 1.68. The mean age at the onset of the symptoms was 11+/-2.3 years (5-16 years). The age of onset was inferior to 10 years in 25 % of the children. The delay before management was superior to 1 year in 25% of cases. The initial symptoms were dominated by diarrhea (95%). Perineal manifestations were present at diagnosis in 30% of children and extra-digestive manifestations in 53%. Ileocolonic localization was the most frequent (46%). The initial disease flare was moderate in 83% of cases. The treatment was medical in 77 % of cases, nutritional and medical in 18.5%. Maintenance therapy was instituted in 86% of cases and consisted essentially in azathioprin (62%). The mean follow-up was 3 years and 4 months. 60% of the children had at least one acute flare. During evolution, 7% of children had anoperineal surgery and 11% an intestinal resection. CONCLUSION: Crohn's disease seems rare in Tunisia. The time of diagnosis is often delayed. The management is based on immunosuppressive therapy and nutritional support.

[Epidemiology of rotavirus gastroenteritis among children under 5 years of age in Tunisia - results of sentinel hospital surveillance 2009 to 2011]. / Épidémiologie des gastroentérites à rotavirus chez les enfants âgés de moins de cinq ans en Tunisie - Résultats de la surveillance sentinelle hospitalière 2009 à 2011.

BACKGROUND: Rotavirus is the major cause of severe acute gastroenteritis among young children. The objectives of this study were to assess the epidemiology, clinical and virological features of community-acquired rotavirus acute gastroenteritis, in children under 5 years of age, hospitalized in Tunisia. METHODS: A multicenter prospective observational study was conducted from April 2009 to March 2011, in 11 sentinel pediatric departments. Clinical data and stool samples were collected for all children under 5 years, admitted for acute gastroenteritis. Rotavirus was detected by Elisa immunoassay test and genotyped for G and P by semi-nested multiplex RT-PCR. RESULT: A total of 621 children were enrolled in this study. Rotavirus was detected in 30.3% of cases (95% CI [26.7-33.9]). The estimated incidence rate of rotavirus acute gastroenteritis was 11 cases/100,000 child-years (95% CI [9.43-12.57]). This infection affected predominantly children aged under 24 months, and occurred mainly in winter (55.3%). Vomiting, fever and dehydration were observed in 79.6%, 69.5% and 57% respectively. Genotype analysis identified four G types (G1, G2, G3 and G4) and 4 P types (P[4], P[6], P[8] and P[9]). The most common G/P combination was G3P[8] (24.4%), followed by G4P[8] (13.3%) and G1P[8] (6.5%). CONCLUSION: These results highlight the frequency and potential severity of rotavirus acute gastroenteritis in pediatric hospital settings. The present study could provide a sufficient database to make a decision related to the introduction of rotavirus vaccine in Tunisian national immunization program.

La(0.7)Sr(0.3)MnO3 nanoparticles based ultra-high sensitive ammonia chemical sensor.

A facile, reliable, reproducible and ultra-high sensitive aqueous ammonia chemical sensor has been fabricated based on the utilization of La(0.7)Sr(0.3)MnO3 nanoparticles (LSMO NPs), as efficient electron mediators, and reported in this paper. The LSMO NPs were prepared by hydrothermal protocol followed by the annealing process and characterized in detail in terms of their mophological, structural and compositional properties. The I-V technique based aqueous ammonia sensor exhibits an ultra-high sensitivity of 494.68 +/- 0.01 microA cm(-2)mM(-1) and very low-detection limit of 0.2 microM with a response time less than 10 s. To the best of our knowledge, this is the first report in which LSMO is used as an efficient electron mediator for the fabrication of aqueous ammonia chemical sensor. Moreover, by comparing the literature, it is confirmed that the fabricated sensor exhibits highest sensitivity towards the detection of aqueous ammonia. This LSMO nanomaterial based research broadens the range of efficient electron mediators utilized for the fabrication of ultra-high sensitive chemical sensors.

Digestive malacoplakia in children: case report.

Malacoplakia is a form of chronic granulomatous inflammatory reaction that rarely affects the pediatric age group. The gastrointestinal system is the second most common site for the occurrence of malacoplakia. We report the case of a 9-year-old girl who was hospitalized for abdominal pain, chronic diarrhea, and rectal hemorrhage. The endoscopic examinations and histopathology confirmed the diagnosis of intestinal malacoplakia. We successfully treated her with oral levofloxacin. This disease does not have any specific clinical or biological signs, and the diagnosis is exclusively based on histology.

[Evolution of group A Rotavirus strains circulating in Tunisia over a 3-year period (2005-2007)]. / Évolution des souches de Rotavirus du groupe A en circulation en Tunisie sur une période de trois ans (2005-2007).

BACKGROUND: Rotaviruses are the most frequent agents associated with diarrhoea in children worldwide. Analysis of mobility of the 11 segments of genomic RNA by polyacrylamide gel electrophoresis (PAGE) yields a pattern which is characteristic for a particular rotavirus isolate. The group A rotaviruses can be further characterized by analysis of VP7 and VP4 genes specificities, responsible for rotavirus classification into G and P genotypes, respectively. The aim of the present study was to determine the evolution of group A Rotavirus strains circulating in Tunisia over a 3-year period (2005-2007). MATERIAL AND METHODS: A total of 1503 stool samples collected from children less than five years old, consulting or hospitalised in Tunisia for diarrhoea between 2005 and 2007, were screened for the presence of group A Rotaviruses. Rotavirus-positive specimens were further analyzed by PAGE and G/P-genotyped by multiplex semi-nested RT-PCR. RESULTS: Rotaviruses were detected in 323 stool samples over 1503 (21 %). Long electropherotypes predominated in Tunisia during the whole period of study (N=158 vs N=82 short electropherotypes). VP7 genotyping showed the cocirculation of five different genotypes: G1, G2, G3, G4 and G9. VP4 typing detected four different P-genotypes: P[8], P[4], P[6] and P[11]. Rotavirus strains with G3P[8] specificity were predominating in Tunisia in 2005 and 2006, replaced by G2P[4] strains in 2007.

Relationship between electropherotypes and VP7/VP4 genotypes of group A rotaviruses detected between 2000 and 2007 in Tunisian children.

BACKGROUND: Rotaviruses are the most frequent agents associated with diarrhoea in children worldwide. Analysis of mobility of the 11 segments of genomic RNA by polyacrylamide gel electrophoresis (PAGE) yields a pattern which is characteristic for a particular rotavirus isolate. The group A rotaviruses can be further characterized by analysis of VP7 and VP4 genes specificities, responsible for rotavirus classification into G and P genotypes, respectively. The aim of the present study was to detect a relationship between electropherotype pattern and molecular characteristics of the rotavirus strains. MATERIAL AND METHODS: Were analyzed 278 rotavirus-positive specimens by PAGE and G/P-genotyped by multiplex semi-nested RT-PCR. Pearson's correlation tests were used for statistical analysis. RESULTS: Twelve different electropherotypes were visualized, eight with a long profile (186 cases) and four with a short one (87 cases). Concerning VP7 types, G2 viral strains were found to be predominant and were detected in 91 specimens (32.7%). Strains with G1, G3, G4, G8 and G9 specificities were detected in 62 (22.3%), 82 (29.5%), 13 (4.7%), two (0.7%) and seven cases (2.5%), respectively. The results of VP4 genotyping showed a predominance of P[8] genotype which comprised half of the strains identified (139 cases, 50%). VP4 P[4], P[6] and P[11] were found in 83 (29.9%), 31 (11.1%) and 11 (4.0%) specimens, respectively. A high rate of mixed strains was also found (1.8% mixed electropherotypes, 7.6% G-mixed and 5% P-mixed strains). Electropherotype pattern of rotavirus strains was significantly correlated with VP7 genotype (p=0.018) and with VP4 genotype specificities (p<0.001).

[Herpetic meningoencephalitis and acute disseminated encephalomyelitis: magnetic resonance imaging sequence]. / Méningo-encéphalite herpétique et encéphalomyélite aiguë disséminée : séquence en imagerie par résonance magnétique.

We report a case of herpetic encephalitis in a 2-year-old girl. Diagnosis was made at 1st by clinical symptoms and MRI and confirmed by lumbar puncture. Forty days later, new neurologic symptoms appeared and MRI diagnosed acute disseminated encephalomyelitis. MRI better demonstrates CNS abnormalities in herpetic encephalitis and may play a major role as a 1st step in early diagnosis, in particular for acute disseminated encephalomyelitis.

IgA anti-actin antibodies in celiac disease.

AIMS: The purpose of this study was to determine the sensitivity and specificity of IgA anti-actin antibodies (IgA-AAA) for celiac disease (CD), to investigate their usefulness as a marker of compliance in CD patients to the gluten-free diet (GFD), and to assess the relationship between their presence in the sera of CD patients and severity of intestinal mucosal damage. PATIENTS AND METHODS: A total of 182 patients with CD were studied: 63 patients were untreated; 50 patients were following a strict GFD; and 69 patients were non-compliant with a GFD. IgA-AAA was detected using a homemade enzyme-linked immunosorbent assay (ELISA). RESULTS: IgA-AAA showed a sensitivity of 41.3% and a specificity of 71.4% for a diagnosis of CD. In children, the frequency of IgA-AAA detection was lower in those following a strict GFD (23.1%) compared with untreated patients (39.4%) and those not complying with a GFD (32.5%). In patients following a strict GFD, IgA-AAA detection was significantly less frequent in children than in adults (23.1% vs. 58.3%, respectively; P<0.001). IgA-AAA was found in 17 out of 52 CD patients with total villous atrophy (32.7%), and in one out of 11 patients with subtotal villous atrophy (9%). CONCLUSION: IgA-AAA cannot replace anti-endomysium and anti-tissue transglutaminase antibodies in the diagnosis algorithm of CD, but it can serve as a reliable marker of severe intestinal mucosal damage in CD patients.

Frequency of Mediterranean mutation among a group of Saudi G6PD patients in Western region-Jeddah.

Glucose-6-phosphate dehydrogenase deficiency (G6PD), a common human enzymatic defects characterized by extreme molecular and biochemical heterogeneity is found to have a variable frequency in different regions. The molecular basis of polymorphic variants in Saudi Arabia have yet to be fully addressed to. Accordingly, a study was designed to determine the frequency of G6PD gene mutations in G6PD deficient cases. From forty-seven unrelated G6PD-deficient subjects, DNA was extracted individually from peripheral blood samples and exons 6 and 7 of the G6PD gene were amplified by PCR. Mutation analysis was carried out by using conformation sensitive gel electrophoresis (CSGE), followed by direct DNA sequencing. The results showed definite altered CSGE patterns. Two mutations were resolved in exon 6 of G6PD gene; Mediterranean mutation and Sibari mutation, not previously reported so far; while no mutation was detected in exon 7. The frequency of exons 6 mutations responsible for G6PD deficiency (Mediterranean type) is reported for the first time from this region, with a figure of 50.1%. The absence of other mutations in exon 7 causing G6PD deficiency points to the low genetic diversity in the studied population.

[Treatment of steroid-resistant idiopathic nephrotic syndrome]. / Traitement du syndrome néphrotique idiopathique corticorésistant.

Idiopathic nephrotic syndrome (INS) is the most frequent glomerular nephropathy in children. The response to corticoids distinguishes steroid-sensitive nephrotic syndrome (SSINS), by far the most frequent (90% of cases), from steroid-resistant nephrotic syndrome (SRINS). The steroid resistance of nephrotic syndrome is defined by the absence of remission after a full dose of oral corticosteroid therapy for 1 month followed by 3 pulses of intravenous methylprednisolone. Actually, INS constitutes a heterogeneous nosologic entity. Currently, within the SRINS, there are 2 forms that vary greatly in their physiopathology and prognostics: immunologic or sporadic forms, which can be improved by immunosuppressive agents and the genetic or familial forms, which do not respond to any immunosuppressive therapy and usually evolve to end-stage renal insufficiency. In these genetic forms, renal transplantation is the only therapeutic alternative. The aim of this article is to review treatment of SRINS and to propose a management strategy.