Children with celiac disease and high tTGA are genetically and phenotypically different

AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD     

In vitro osteoclast resorption of bone substitute biomaterials used for implant site augmentation: a pilot study

PURPOSE: This observational study examined the resorptive behavior of normal neonatal rabbit osteoclasts grown on slices of bovine cortical bone as compared to samples of commercially available bone substitute biomaterials. It also examined the surface characteristics of these materials. MATERIALS AND METHODS: The 11 materials tested fell into 3 groups: (1) bone-derived, including freeze-dried human rib block, human demineralized freeze-dried bone, and deproteinated bovine bone; (2) synthetic hydroxyapatites (HA); and (3) synthetic non-HA, including coated methacrylates and coated silica glass. After 4 days in culture, 1 group of samples of each material underwent scanning electron microscopy (SEM) to evaluate resorptive pitting versus controls, while another group underwent tartrate-resistant acid phosphatase staining and light microscopy to examine osteoclast numbers and morphology. The 2 bovine-derived HA materials also underwent immunohistochemical staining and surface chemistry analysis. RESULTS: While most of these materials supported osteoclast attachment, some spreading, and survival in culture, only the bone-derived materials, with the exception of sintered deproteinated bovine bone, showed large scalloped-edged resorption pits with trails and exposed collagen when examined by SEM, although not to the same extent as unprocessed natural bone material. The HA materials and the sintered deproteinated bovine bone showed evidence of etching with smaller pits but no evidence of resorptive trail formation. The non-HA materials showed no evidence of pit formation or trails. Under immunohistochemical staining, Bio-Oss appeared to be positive for type I collagen after osteoclast activity on its surface, while Osteograf/N showed no positive staining. Surface chemistry analysis revealed nitrogen present in Bio-Oss specimens (0.17% to 0.47%), while there was no nitrogen detected in the Osteograf/N (0.00%); the percent nitrogen observed in normal bovine bone controls was 6.01% to 9.25%. DISCUSSION: The bone-derived materials supported osteoclast activity on the material surface in a way that facilitated formation of the more complex resorption pits in vitro. Assuming the rate of pit formation observed in vitro mimics that observed in vivo, the quantity and type of osteoclastic remodeling seen on non-bone-derived materials--and perhaps sintered bone-derived materials--would be extremely slow to negligible. Physiologic removal of non-bone-derived bone substitutes in vivo may occur by methods other than osteoclast resorption. CONCLUSIONS: Allogenous and xenogenous bone-derived materials that undergo delayed physiologic resorption may be more appropriately used with a staged surgical approach when used in sites intended to support osseointegrated dental implants. The combination of collagen staining and the presence of nitrogen suggest that there may be residual protein in Bio-Oss.     

Predictive factors associated with complete pathological response after neoadjuvant treatment for rectal cancer

PurposeA proportion of 10 to 30% of patients treated by chemoradiotherapy followed by total mesorectal excision surgery for a locally advanced rectal cancer can achieve a complete pathological response. We aimed to identify predictive factors associated with complete pathological response or no response and to assess the impact of each response on survival rates.Patients and methodsPatients treated with long course chemoradiotherapy for locally advanced and/or node positive rectal cancer from 2010 to 2016 were retrospectively reviewed. Statistical analysis was carried out to determine predictors of tumor regression and treatment outcomes.ResultsRecords were available on 70 patients. In the univariate analysis, clinical factors associated with complete tumor response were tumor mobility in digital rectal examination (P = 0.047), a limited parietal invasion (P = 0.001), clinically negative lymph node (P < 0.001) and a circumferential extent greater than 50% (P = 0.001). On the other hand, a T4 classification and an endoscopic tumor size greater than 6 cm were associated with no response to treatment (P = 0.049 and P = 0.017 respectively). On multivariate analysis, T2 clinical classification and N0 statement before treatment were independent predictive factors of pathologic complete response (P < 0.001 and P = 0.001) and a delayed surgery after 12 weeks was associated with no response to treatment (P = 0.001).ConclusionThe identification of predictive factors of histological response may help clinicians to predict the prognosis and to propose organ preservation for good responders.     

Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction in Tunisian patients

BACKGROUND: Numerous polymorphisms of the apolipoprotein B (APOB) gene have been described. Particularly, the insertion/deletion (Ins/Del) polymorphism located in the coding part of the signal peptide of apoB, associated with modification of lipid concentrations and the risk of coronary artery disease and/or myocardial infarction (MI), has been reported in the general population. Moreover, conflicting results emerge from the literature and suggest that the effect is context-dependent. In the present study, the first investigation of the Ins/Del polymorphism of the APOB gene in Tunisian patients with MI, we examined a possible association between this polymorphism and MI in a subgroup of the Tunisian population. METHODS: A total of 318 Tunisian patients with MI and 368 healthy controls were included in the study. Genomic DNA was extracted from white blood cells, and the Ins/Del polymorphism was determined by electrophoresis in polyacrylamide gels after PCR amplification. A binary logistic regression analysis was performed to test how the association between MI and Ins/Del polymorphism is independent from confounding factors. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 7.2% for the Del/Del genotype, 39.6% for the Ins/Del genotype, and 53.1% for the Ins/Ins genotype. Controls had a frequency of 3.0% for the Del/Del, 32.1% for the Ins/Del and 64.9% for the Ins/Ins genotype (chi2=12.93, p=0.002). The MI patient group showed a significantly higher frequency of the Del allele compared to controls (27.1% vs. 19.1%; chi2=12.50, p=0.0004). In comparison to the Ins/Ins homozygotes, the odds ratio (95% confidence interval) for MI was 1.51 (1.09-2.07) for Ins/Del heterozygotes and 2.95 (1.40-6.22) for Del/Del homozygotes. In multivariate analysis, age (p=0.001), smoking (p<0.001), hypertension (p=0.001), diabetes mellitus (p<0.001), and dyslipidemia (p=0.01) were independent correlates of the presence of MI, whereas the Ins/Del polymorphism (p=0.330) was not an independent predictor of MI. CONCLUSIONS: The present study shows a significant but not independent association between the Ins/Del polymorphism of the APOB gene and MI in the Tunisian population.     

Treatment of diabetic foot lesions in hospital: results of 2 successive five-year periods, 1989-1993 and 1994-1998

OBJECTIVES: To assess the impact of an educational training program we initiated in 1994 for GPs about diabetic foot ulcer (DFU) management, we compared the rate and level of lower limb amputation (LLA) in diabetic patients performed in our unit between two consecutive five-year periods, 1989-1993 and 1994-1998. PATIENTS AND METHODS: During the first period, 132 patients with 163 lesions (9.2% of the total admissions for diabetes) were compared with 176 with 183 lesions (10.5%) during the second period. Patients' mean age was the same in both periods: 59.6 +/- 11.7 in 1989-1993 and 58.3 +/- 13.1 in 1994-1998 [Not statistically significant, NS]. RESULTS: Patients age, sex ratio, type of diabetes and severity of the lesion (as assessed according to Wagner classification) were essentially the same during the two periods. Most of the foot lesions ( approximately 90%) were purely neuropathic or neuro-ischaemic, with no change in repartition between the two periods. Primary healing was 59.1% in the 1st period and 56.8% in the second. No change in minor and major amputation rate was observed between the 1st period (14.4 and 15.9%, respectively) and the second (11.4 and 16.5%, respectively). The in-hospital mortality rate was unchanged (9.1 vs 8.5%, NS), while the percentage of patients who left hospital against medical advice and dropped out of follow up increased from 1.5 to 6.8% (p<0.04). Mean length of hospitalisation was identical, about 43 days. CONCLUSIONS: In spite of implementing educational program for GPs, no improvement in the DFU management was noted as emphasised by absence of any significant change in amputation rate before (1st period) and after initiating the program (2nd period). These disappointing results can be explained by several factors: weakness of our educational program, lack of motivation from GPs, absence of a structured multidisciplinary prevention approach. The main problem, common to developing countries, remains the insufficiency of financial resources. Moreover, civil disturbances can make the problem more difficult to manage, as in Algeria since 1991.     

P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of l-carnitine

Amethopterin (methotrexate, MTX) is an antimetabolite and antifolate drug with antiflammatory properities and is used to treat autoimmune diseases, such as psoriasis, rheumatoid arthritis and certain types of cancer, such as breast, lymphoma and lung. The present study aimed to study the changes in P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating the role of l-carnitine. A total of 36 male albino rats were equally divided into six groups: the first and second groups were the control and l-carnitine groups respectively while the 3rd group was amethopterin rat group; the 4th and 5th groups were co- and post-treated amethopterin rat with l-carnitine respectively and the 6th group was self treated amethopterin rat group. Our results shows that lung in amethopterin-treated rats showed many of histopathological alterations as severe to strong alveolar damage in the form of collapsed alveoli and strong thickened interalveolar septa with heavy infiltration of inflammatory cells. This damage was increased or remaining in self-amethopterin-treated group. Treatment (co- and post) with l-carnitine were improved in the lung structure that was treated with amethopterin. A significant increase in p53 and CD68 and decrease in Bc1-2 immunoreactivity in the lung in amethopterin group is observed when compared with the control group. However, treatment of rats with l-carnitine decreased the intensity of P53-ir and CD68-ir and increased the intensity of Bcl-2 in lung when compared with amethopterin rat group. Co-treatment with l-carnitine improved lung damage induced with amethopterin.     

Interobserver variability in ultrasound assessment of thyroid nodules

The first diagnostic tool for thyroid disease management is ultrasound. Despite its importance, ultrasound is an extremely subjective procedure that requires a high level of performance skill. Few studies have assessed thyroid ultrasound performance and its effectiveness, particularly the variability between observers in the assessment of ultrasound images. This study evaluated the variability in ultrasound assessments and diagnoses of thyroid nodules between 2 radiologists. In this retrospective study, 75 thyroid nodules in 39 patients were reviewed by 2 experienced radiologists. The nodule composition, margin, shape, calcification, and vasculitis were determined using echogenicity. The study evaluation included these 5 assessments and the final diagnosis. Interobserver variation was determined using Cohen kappa statistics. The interobserver agreements in the interpretation of echogenicity, shape, and margin were fair (κ = 0.21–0.40), whereas there were substantial agreements for vascularity and calcification (κ = 0.62–0.78). The agreements between the observers for individual ultrasound features in this study were the highest for vascularity and the presence/absence of calcification. The interobserver reproducibility for thyroid nodule ultrasound reporting was adequate, but the diagnostic evaluation ability of the observers was inconsistent. The variability in the interpretation of sonographic features could influence the level of suspicion of thyroid malignancy. This study emphasizes the need for consistency in the training of sonographic interpretation of thyroid nodules, particularly for echogenicity, shape, and margin.