Evidence of very delayed clinical reactions to cow's milk in cow's milk-intolerant patients

BACKGROUND: In patients with cow's milk protein intolerance (CMPI), delayed clinical reactions to cow's milk (CM) ingestion may be misdiagnosed if the clinical symptoms are not "classical" and there is a long time lapse between ingestion of CM and the clinical reaction. The aim was to evaluate the clinical outcome of CMPI in a cohort of CM-intolerant children, with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge. METHODS: Eighty-six consecutive patients (44 boys, 42 girls) with new CMPI diagnoses were enrolled; median age at diagnosis was 4 months. Patients were followed up for a mean period of 40 months. In all patients, CMPI diagnosis was made on the observation of symptoms, their disappearance after elimination diet, and their reappearance on double-blind CM challenge. At CMPI diagnosis, immunologic tests to demonstrate IgE-mediated hypersensitivity were performed. After 12 months of CM-free diet, CM tolerance was re-evaluated with a CM challenge continued at home for up to 30 days, according to a double-blind, placebo-controlled method. Patients who did not achieve CM tolerance continued a CM-free diet and subsequently underwent yearly CM challenge. RESULTS: The percentages of CMPI patients who became CM-tolerant after 1, 2, and 3 years of CM-free diet were 30%, 54.5%, and 70%, respectively. At the end of the follow-up period, 26/86 subjects showed persistent CMPI; these patients had a higher percentage of positivity of total serum IgE (P<0.05), RAST (P<0.01), and cutaneous prick tests for CM antigens (P<0.001) than all the others. At CMPI diagnosis, all patients had a clinical reaction within 72 h from the beginning of the CM challenge; at the subsequent "cure" challenges, we observed patients who first reacted to CM more than 72 h after ingestion. In total, 10 out of 86 patients showed "very delayed reactions"; in these patients, the mean time between the beginning of CM challenge and the onset of a clinical symptom was 13.3 days (range 4-26 days). The number of "very late reactors" increased from the first to the third of the "cure" CM challenges, performed at yearly intervals. The "very delayed" CMPI manifestations in these subjects were constipation (five cases), wheezing (two cases), dermatitis plus constipation (two cases), and dermatitis alone (one case); in 6/10 patients, the symptoms observed at the "cure challenge" were different from those at CMPI onset. CONCLUSIONS: Very delayed clinical reactions to reintroduction of CM in the diet can occur in CMPI patients; thus, accurate follow-up and frequent outpatient observation in patients with a long history of CMPI are probably more useful and safer than prolonged CM challenge.     

Physical Similarity and Twin Resemblance for Eating Attitudes and Behaviors: A Test of the Equal Environments Assumption

The Equal Environments Assumption (EEA) in twin studies of eating pathology was investigated by examining the hypothesis that twin resemblance for eating attitudes and behaviors is affected by their degree of physical similarity. Eating attitudes and behaviors were assessed in 338 female adolescent twin pairs with a revised version of the Eating Disorder Inventory (EDI). General physical similarity as well as body size/shape similarity were assessed using ratings of color photographs, ratings of body shape, and body mass index. All physical similarity assessments were conducted blind to twin zygosity. Significant associations between physical similarity and twin similarity for eating attitudes and behaviors were not found. Mean EDI within-twin pair absolute difference scores did not differ significantly among more versus less physically-similar groups. Additionally, correlation and regression analyses failed to find a significant association between EDI absolute difference scores and physical similarity indices. The current findings provide support for the EEA in twin studies of eating attitudes and behaviors.     

Genetic and environmental influences on adolescent substance use and abuse

The inheritance of substance use and abuse among adolescents was investigated in a sample of 626 male and female 17-year-old twin pairs. Both licit (tobacco) and illicit (e.g., marijuana, amphetamines) substance use and abuse was assessed and analyzed using standard biometric methods. The heritability of use and abuse of illicit substances was modest (25% or less), whereas the heritability of tobacco use and nicotine dependence was substantial (40% to 60%). There was no evidence that gender moderated the strength of genetic influences. Shared environmental influences were substantial for all substance use measures. The finding of greater genetic influence on the use and abuse of a licit substance than on the use and abuse of illicit substances suggests that inherited risk to drug abuse is considerably moderated by environmental control, at least in adolescence. The finding of significant environmental influences on all substance use measures underscores the importance of intervention on early adolescent substance use, a known predictor of adult substance abuse and dependence.     

Genetic and Environmental Influences on Parent–Child Conflict and Child Depression Through Late Adolescence

Few studies have investigated potential gender differences in the genetic and environmental influences on the prospective associations between parent–child conflict and later depression, a notable gap given substantial gender differences in rates of depression and suggestive evidence of differences in the etiology of depression among females and males. To fill this gap, we evaluated whether the prospective relationship between parent–child conflict and major depressive disorder symptoms varied as a function of parent–child gender composition. A combined twin and adoption sample was used (53% female; 85% European ancestry), containing 1,627 adolescent sibling pairs (789 monozygotic twin pairs, 594 dizygotic/full-biological pairs, 244 genetically unrelated pairs) with assessments at two time points in adolescence (approximate ages 15 and 18). Prospective associations between parent–child conflict and subsequent adolescent depression were explained predominately through common genetic influences for mother–daughter and mother–son pairs but less so for father–daughter and father–son pairs. Results support the notion that processes of gene–environment correlation involved in the prospective associations between parent–child conflict, and later adolescent depression appear to be less relevant to father–child relationships in comparison to mother–child relationships. Notably, results did not show that parent–child conflict was more relevant to the etiology of major depressive disorder (MDD) for girls than boys; gender differences in depression do not appear to be due to differences in the associations between parent–child conflict and child depression.     

Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK

BRCA1 and BRCA2 are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms (SNPs) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women with BRCA1/BRCA2 mutations. BRCA1/2 mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios (OR) and risk allele frequencies, we calculated an overall breast cancer risk SNP score (OBRS) for each woman. The relationship between OBRS and age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell's C concordance statistic. In BRCA1 mutation carriers we found no association between OBRS and age at breast cancer onset: OR for the lowest risk quintile compared to the highest was 1.20 (95% CI 0.82–1.75, Harrell's C = 0.54), but in BRCA2 mutation carriers the association was significant (OR for the lowest risk quintile relative to the highest was 0.47 (95% CI 0.33–0.69, Harrell's C = 0.59). The 18 validated breast cancer SNPs differentiate breast cancer risks between women with BRCA2 mutations, but not BRCA1. It may now be appropriate to use these SNPs to help women with BRCA2 mutations make maximally informed decisions about management options.     

Human serum antibodies against shared antigens of different stages of<Emphasis Type="Italic"> Trichinella spiralis</Emphasis>: relevance of glycan and protein epitopes

Taking into account that antibodies against the surface antigens of newborn larvae (anti-NBL Abs) present in sera from individuals with chronic trichinellosis recognize antigenic determinants of the excretory-secretory muscle larva products (ML-ESP), and that these products are mainly glycoproteins, the aim of this work was to assess the frequency of anti-NBL Abs in sera from individuals with acute and chronic trichinellosis, to analyse the relevance of glycan and protein epitopes of the ML-ESP in the cross-reactivity phenomenon, and its correlation with the host's serum response towards these products. Anti-NBL surface Abs were determined in sera by indirect immunofluorescence. The degree of recognition by serum and purified anti-NBL Abs was evaluated comparatively before and after chemical deglycosylation of ML-ESP by immunoelectrotransfer blot assay. Results showed that 64% of the sera from individuals with acute trichinellosis and 35% of those belonging to the chronic phase had anti-NBL Abs, and also that the protein epitopes are the major ones responsible for the cross-reactivity phenomenon involving the ML-ESP and the NBL surface during both phases of the infection, while glycan epitopes are immunodominant in the stimulation of the host's immune system. A modulatory phenomenon in the immune response generated towards Trichinella spiralis NBL driven by the ML-ESP is postulated.     

Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients

To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic steatohepatitis, in HCV-infected subjects IFN-alpha and -beta mRNA levels were significantly lower, whereas IFN-gamma, IFNAR-1, STAT1alpha IRF-1, and IL-18 mRNA were upregulated. Moreover, IFN-gamma mRNA steady state levels were correlated positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL-18-specific mRNA, viral load was not related to liver injury. IFN-gamma and IRF-1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN-alpha and -beta mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN-gamma system and a downregulated IFN-alpha and -beta system, probably due to a mixed effect exerted by HCV-specific and inflammatory non-specific factors.     

Enhancing Guided Tissue Regeneration of Periodontal Defects by Using a Novel Perforated Barrier Membrane

Background: The present study was designed to determine whether exclusion of the gingival connective tissue (CT) and periosteum with contained stem cells has a positive or negative effect on periodontal regeneration by comparing the use of a novel modified perforated collagen membrane with a traditional cell occlusive barrier membrane. Methods: Twenty non‐smoking patients with severe chronic periodontitis were included in the study. Single deep intrabony defects from each of the patients were randomly divided into two groups, as follows: occlusive bovine collagen membranes (OM control group, 10 sites) and modified perforated bovine collagen membranes (MPM test group, 10 sites). Plaque index, gingival index, probing depth (PD), clinical attachment level (CAL), defect base level (DBL), and crestal bone level (CBL) were measured at baseline and were reassessed at 6 and 9 months after therapy to evaluate the quantitative changes in the defect. Results: At 6‐ and 9‐month observation periods, the MPM‐treated sites showed a statistically significant improvement in PD reduction and CAL gain compared with the OM control group. DBL was significantly reduced with no significant difference between the two groups at 6‐ and 9‐month observation periods. CBL was significantly higher in the MPM group when compared with that of the OM group at both observation periods. The postoperative differences between the two groups were 2 and 1.7 mm at 6 and 9 months, respectively, in favor of the MPM‐treated sites. Conclusions: The present study demonstrated enhanced clinical outcomes when using novel MPMs compared to OMs in guided tissue regeneration procedures. These results may be affected by the penetration of gingival CT contained stem cells and periosteal cells and their differentiation into components of the attachment apparatus.     

Changes in the orientation of knee functional flexion axis during passive flexion and extension movements in navigated total knee arthroplasty

Purpose

Recently, the functional flexion axis has been considered to provide a proper rotational alignment of the femoral component in total knee arthroplasty. Several factors could influence the identification of the functional flexion axis. The purpose of this study was to analyse the estimation of the functional flexion axis by separately focusing on passive flexion and extension movements and specifically assessing its orientation compared to the transepicondylar axis, in both the axial plane and the frontal plane.

Methods

Anatomical and kinematic acquisitions were performed using a commercial navigation system on 79 patients undergoing total knee arthroplasty with cruciate substituting prosthesis design. The functional flexion axis was estimated from passive movements, between 0° and 120° of flexion and back. Intra-observer agreement and reliability, internal–external rotation and the angle with the surgical transepicondylar axis, in axial and frontal planes, were separately analysed for flexion and extension, in pre- and post-implant conditions.

Results

The analysis of reliability and agreement showed good results. The identification of the functional flexion axis showed statistically significant differences both in relation to flexion and extension and to pre- and post-implant conditions, both in frontal plane and in axial plane. The analysis of internal–external rotation confirmed these differences in kinematics (p < 0.05, between 25° and 35° of flexion).

Conclusions

The identification of the functional flexion axis changed in relation to passive flexion and extension movements, above all in frontal plane, while it resulted more stable and reliable in axial plane. These findings supported the possible clinical application of the functional flexion axis in the surgical practice by implementing navigated procedures. However, further analyses are required to better understand the factors affecting the identification of the functional flexion axis.

Level of evidence

IV.