Identification of familial colorectal cancer and hereditary colorectal cancer syndromes through the Dutch population-screening program: results ofa pilot study

Objectives: In 2014, a population-screening program using immuno-faecal occult blood testing (I-FOBT) has started in the Netherlands. The aims of this study were to evaluate the proportion of individuals in the Dutch screening program with a positive I-FOBT that fulfill the criteria for familial colorectal cancer (FCC) and to evaluate the proportion of participants that needs genetic counseling or colonoscopic surveillance.

Material and methods: This retrospective observational study was performed in two large hospitals. Individuals aged between 55 and 75 years with a positive I-FOBT that underwent colonoscopy were included. A detailed family history was obtained in all individuals.

Results: A total of 657 individuals with a positive I-FOBT test underwent colonoscopy. A total of 120 (18.3%) participants were found to have a positive family history for CRC, 20 (3.0%) fulfilled the FCC criteria, 4 (0.6%) the Bethesda guidelines and 1 (0.2%) participant the Amsterdam criteria. Multiple adenomas (>10) were found in 21 (3.2%) participants. No cases of serrated polyposis were identified. Based on these criteria and guidelines, a total of 35 (5.3%) required referral to the clinical geneticist and the relatives of 20 (3.0%) participants should be referred for surveillance colonoscopy.

Conclusion: Obtaining a detailed family history at the time of intake of participants with a positive I-FOBT in the Dutch surveillance program increased the identification of participants with familial CRC.     

Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs

Background

The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need.

Purpose

In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed.

Methods

Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays.

Results and Conclusion

Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P_app for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P_app for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at ‘the door step’ of absorption sites.

     

Left ventricular function and left atrial volumes in rheumatoid arthritis patients: Subclinical cardiac involvement and relation to seropositivity

BackgroundLeft ventricular (LV) dyfunction with preserved ejection fraction has been associated with increased mortality. Left atrium (LA) modulates LV filling and plays a role in maintaining cardiac function. Cardiovascular disease is a leading cause of death in rheumatoid arthritis (RA).Aim of the workTo study the left atrium modulating the left ventricular filling and to investigate its relation with disease activity to detect subclinical early cardiac affection in RA patients.Patients and methods45 RA patients and 30 control were studied. The disease activity score (DAS28) was calculated. Conventional and tissue Doppler imaging (TDI) and strain (S) and strain rate (SR) analysis by two-dimensional speckle tracking of LA were conducted.ResultsThe 45 female patients mean age was 38.8 ± 8.7 years, disease duration was 7.3 ± 6.2 years and mean DAS28 was 4.1 ± 0.9. Regarding the LA emptying fractions, only the 2 LA passive emptying fraction (PEF) and total emptying fraction (TEF) were significantly lower in patients compared to control (p = 0.01 and p = 0.025 respectively). The LA expansion index (EI) was significantly reduced in patients compared to control (p = 0.009). Regarding TDI-derived mitral annular velocities, lateral e’ and s as well as SRe (l/s) were significantly slower in patients compared to control (p = 0.001, p = 0.02 and p < 0.0001 respectively). Rheumatoid factor (RF) was significantly inversely related to TDI laterale, TDI laterals, and strain rate e, LA-PEF, LA-EI and LA-TEF.ConclusionRA patients had alteration in LV longitudinal myocardial function and more LA stiffness. Cardiac affection is more in seropositive patients.     

The anti-inflammatory effect of milk and dairy products on periodontal cells: an in vitro approach

Clinical Oral Investigations - Milk can reduce intestinal tissue damage in colitis models, and protects infants against necrotizing enterocolitis. However, whether milk can decrease inflammation...     

A new series of Schiff base derivatives bearing 1,2,3‐triazole: Design,synthesis, molecular docking,and α‐glucosidase inhibition

A series of new Schiff bases bearing 1,2,3‐triazole 12a ? o was designed, synthesized, and evaluated as α‐glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α‐glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α‐glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α‐glucosidase.     

Blood bezoar causing obstruction after laparoscopic Roux-en-Y gastric bypass

INTRODUCTION

Bowel obstruction is a known complication after bariatric surgery especially Roux-en-Y gastric bypass. The known etiologies include internal hernia, jejunojejunostomy stricture, ileus, intussusceptions, superior mesenteric artery syndrome, incarcerated port site hernia, and adhesions. Blood bezoar is a rare cause of small intestinal obstruction after Roux-en-Y gastric bypass.

PRESENTATION OF CASE

We are going to present two cases of small bowel obstruction after Roux-en-Y gastric bypass due to blood bezoar.

DISCUSSION

Blood clot as the etiology of small bowel obstruction after Roux-en-Y gastric bypass is an unusual event. In the presence of postoperative small intestinal obstruction an obstructive blood bezoar should be in differential diagnosis. As any other etiology of postoperative obstruction it should be treated immediately to prevent its adverse lethal complications.

CONCLUSION

The best way for prevention of blood bezoar is prevention of bleeding at staple line and doing hemostasis at stapler line.     

Bone regeneration performance of surface-treated porous titanium

The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid–alkali (AcAl), alkali–acid–heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.     

Clinical and histological significance of atypical glandular cell on Pap smear

BACKGROUND: Atypical glandular cell (AGC) on Pap smear is uncommon but may represent a variety of benign and malignant lesions. AIM: The aim of this study was to evaluate the association between AGC on Pap smear and significant pathological finding to tailor management protocols. METHODS: Between 2002 and 2005, 60 women with AGC on Pap smears were referred to our colposcopy clinic. Forty-one women underwent colposcopy-directed biopsy, endocervical curettage, endometrial sampling and cervical conisation to determine the cytological and histological correlations of AGC on Pap smears. RESULTS: The mean age of the patients was 46.9 +/- 11.5 years (range, 23-80 years). Of these patients 13 patients (31.7%) were postmenopause and 28 patients (68.2%) were in reproductive age. We found eight (19.5%) significant pathological findings including four (9.7%) high-grade squamous intraepithelial lesion, one (2.4%) adenocarcinoma of uterus, one (2.4%) adenocarcinoma of cervix, one (2.4%) squamous cell carcinoma of cervix and one (2.4%) papillary serous tumour of ovary. CONCLUSION: AGC on Pap smear was associated with a clinically significant diagnosis in approximately 20% of our cases. The women with a diagnosis of AGC on cervicovaginal smear are needed to be evaluated at least with colposcopy, endocervical and endometrial curettage. Clinicians should be careful about the significance of AGC on Pap smears.