Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

BACKGROUND The adenoma detection rate(ADR) is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy. However, adenoma miss rates reach up to 26% and studies have shown that a second inspection of the right colon in retroflected view(RFV) can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV) can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms. In RFV arm colonoscopy was initially performed with SFV, followed by a second inspection of the whole colon in RFV. In the SFV arm first withdrawal was performed with SFV, followed by a second inspection of the whole colon again with SFV. Number, size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n = 101) and SFV(n = 104) arm. In the RFV arm, both polyp detection rate(PDR) and ADR were increased under second inspection in RFV(PDR 1~(st) SFV: 39.8%, PDR 2~(nd)RFV: 46.6%; ADR 1~(st) SFV: 35.2%, ADR 2~(nd) RFV: 42%). Likewise, in the SFV arm,PDR and ADR were increased under second inspection(PDR 1~(st) SFV: 37.5%, PDR 2~(nd) SFV: 46.6%; ADR 1~(st) SFV: 34.1%, ADR 2~(nd)SFV: 44.3%) with no significant differences in ADR and PDR between the SFV and RFV arm. Mean number of adenomas per patient(APP) was increased in the RFV and SFV(APP RFV arm: 1~(st) SFV: 1.71; 2~(nd) RFV: 2.38; APP SFV arm: 1~(st) SFV: 1.83, 2~(nd)SFV:2.2). The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were 5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV. Hence, increased detection is most likely a feature of the second inspection itself but not of the inspection mode.     

Age determines memory for face identity and expression

Background: The recognition of facial expressions is an important component of emotion processing which contributes to interactional behavior. One of the factors highly associated with potential decline of ability in behavioral tasks is age. Methods: We have investigated age‐related changes in facial identity and expression memory of healthy subjects in three age groups: young adults (20–40 years), elderly adults (60–80 years) and, for the first time in the literature, very old adults (over 80 years of age). Using a picture test, photographs of faces with happy or angry expressions were presented to study participants during the encoding task, and the memory for identity and emotional facial expression was investigated in a subsequent recognition task showing emotionally neutral faces. Half of the faces presented in the recognition task were initially shown in the encoding task. Results: Age interacted with the memory process: the ability to recognize both facial identity and emotional expression declined with advanced age. Happy facial expressions were better recognized in all age groups. Although there was a continuous overall decrease in recognition of both happy and angry expressions with advanced age, the effect favoring happy facial expressions was stable also in very old adults. Other factors such as gender or educational level did not affect the memory process for facial expressions. Conclusions: Our findings suggest that age is a significant determinant of memory for facial identity and emotional expression, and that, similar to younger adults, the recognition process of the elderly favors happy emotional facial expressions.     

Comparison of fecal microflora in children with atopic eczema/dermatitis syndrome according to IgE sensitization to food

Atopic eczema/dermatitis syndrome (AEDS) commonly often arises during early infancy. In several intervention studies a beneficial influence on AEDS course of certain intestinal bacteria, administered as 'probiotics', has been described. To evaluate the possible role of the natural intestinal microflora in children with allergic eczema/dermatitis syndrome regarding immediate type hypersensitivity to food allergens, children with food allergy (AAEDS, n = 68) have been compared with children without detectable food allergy (NAEDS, n = 25). All children (n = 93) in preschool age, mean age of 2.6 (+/-1.8) years, diagnosed with AEDS who were treated as inpatients in 2003 in a dermatological hospital were included. The correlation between fecal microflora, parasites and specific immunoglobulin E (IgE) antibodies against common food allergens was analyzed. A similar composition of intestinal microflora in children with AAEDS and NAAEDS was found. The food allergens that were most frequently detected were egg white, cow milk, casein, peanut and hazelnut. Furthermore, a significant association between IgE sensitization against important food allergens and components of the fecal microflora could not be demonstrated. With aging changes occur in the intestinal microbiota [Proteus/Klebsiella and age (rho = -0.607) and Enterococcus and age (rho = -0.428)]. In two subjects of the AAEDS group Blastocystis hominis was found. The composition of natural intestinal microflora in children with AAEDS and NAAEDS was similar. Hence, there is no evidence of a role of the intestinal microflora with regard to the development of infant (food) allergy in children with AEDS. The possible consequences for allergic diseases later in life require further investigation.     

Circadian rhythm and pulsatility of parathyroid hormone secretion in man

OBJECTIVE: We wished to investigate the circadian rhythm and pulsatility of parathyroid hormone (PTH) secretion in man, as conflicting results have been published. DESIGN AND PATIENTS: To investigate the circadian rhythm during daytime, we sampled (a) peripheral blood at hourly intervals in 12 healthy young men from 0900 h until 1700 h. For observation of pulsatility, we sampled (b) peripheral blood at 1-minute intervals for 1 hour in three healthy men and three healthy women (mean 27.7 years, range 21-56 years) and (c) at 1-minute intervals for 30 minutes in 21 patients with surgically confirmed primary hyperparathyroidism (pHPT). MEASUREMENTS: The serum levels of intact PTH were measured by two-site immunoradiometric assay and special care was taken to reduce intra-assay variability, especially at the normal PTH concentration. In series (a), ionized calcium, total calcium and phosphate were also determined. RESULTS: A circadian rhythm during daytime was found for intact PTH in healthy men and women with a nadir at 0930 h and a peak in the afternoon. Ionized calcium and total calcium (protein-adjusted) decreased and phosphate increased in the afternoon. These changes were all statistically significant (P < 0.02). Pulsatility of PTH: Statistical cluster analysis of the data showed no pulsatility either in healthy persons or in patients with primary hyperparathyroidism. In two healthy women and one healthy man slight changes of longer duration were discovered, but no complete pulses. In five patients with primary hyperparathyroidism, larger differences between the highest and lowest concentrations of intact PTH were found, but no complete pulses. CONCLUSIONS: Our data show a significant circadian rhythm during daytime of intact PTH and only minor changes from minute to minute. The alterations in PTH-levels occurred at longer time intervals in healthy persons. In some patients with primary hyperparathyroidism, decreases of PTH-levels were found. The circadian rhythm of PTH may be due to slight changes in calcium or phosphate concentration.     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

The Role of Donor Bone Marrow Infusions in Withdrawal of Immunosuppression in Adult Liver Allotransplantation

We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post-transplantation, with stable graft function. Forty-five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year. Patient and graft survival were similar between the two groups. Although rejection episodes were significantly less in G1 the first 2 years of the study (35% vs. 57%, p = 0.016), there was no significant difference overall (74% vs. 81%, p = 0.14). Until February 2004, 20 patients, 10 in each group, were immunosuppression free for 1-3 years. Approximately 20% of long-term survivors of liver transplantation can successfully discontinue their immunosuppression. DBMC infusions, do not increase this likelihood.     

Association of EGFR Gene Amplification and CDKN2 (p16/MTS1) Gene Deletion in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) can be divided into genetic subsets: approximately one-third of GBM, primarily in older adults, have EGFR amplification; another one-third, primarily in younger adults, have TP53 mutation. The majority of GBM also have homozygous deletions of the CDKN2 (p16/MTS1) gene, resulting in cell cycle deregulation and elevated proliferation indices. We evaluated the relationship between CDKN2 deletions and the GBM subsets as defined by EGFR amplification or TP53 mutation in 70 GBM. Twenty-eight cases (40%) had EGFR amplification, 21 (30%) had TP53 mutation, and 21 (30%) had neither change. CDKN2 deletions were present in 36 (51%) GBM. Of the 28 GBM with EGFR amplification, 20 (71%) had CDKN2 deletion (p = 0.0078). The remaining 16 cases with CDKN2 loss were divided between GBM with TP53 mutations (6 cases) and GBM with neither EGFR amplification nor TP53 mutation (10 cases). Thus, CDKN2 deletions occur twice as commonly in GBM with EGFR amplification (71%) than in GBM with TP53 mutation (29%). CDKN2 deletions occurred in GBM from patients somewhat older than those patients with GBM lacking CDKN2 deletion (mean age 53 vs. 48 years). Specifically among GBM with EGFR amplification, those with CDKN2 deletions also occurred in patients slightly older than those few GBM without CDKN2 deletions (mean age 55 vs. 51 years). The presence of CDKN2 deletions in most GBM with EGFR amplification and in generally older patients may provide one explanation for the potentially more aggressive nature of such tumors.