Emiliano Maresi

Chronic constipation and food intolerance: A model of proctitis causing constipation

Objective Chronic constipation in children can be linked to cows milk intolerance (CMI) but the existence of a food intolerance-dependent proctitis is still debated. The aim of this study was to evaluate the histologic data in patients with food intolerance-related constipation. Material and methods Fifty-two consecutive patients (22 M, median age 4 years) with chronic constipation unresponsive to common treatment were enrolled. All patients were put on a cows milk-free diet for 4 weeks and those uncured on this diet underwent a subsequent 4-week period of oligoantigenic diet. In the patients cured on elimination diet, a subsequent double-blind food challenge was performed to confirm the diagnosis of food intolerance. At entry to the study, routine hemato-chemical and immunologic assays, rectoscopy, and histologic study of the rectal mucosa were performed. In the patients cured on elimination diet, rectal histology was repeated when they were cured. Results Twenty-four patients were found to be suffering from CMI and 6 from multiple food intolerance. These patients had a normal stool frequency on elimination diet, while constipation reappeared on food challenge. The condition of the remaining 22 patients did not improve on elimination diet. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, number of intraepithelial lymphocytes and eosinophils, and number of eosinophils in the lamina propria. Study of the rectal mucus gel layer showed that the food-intolerant patients had a significantly lower thickness than the other subjects studied. In the food intolerant patients, histologic abnormalities disappeared on elimination diet, when the patients were well. Conclusions Food intolerance-related constipation is characterized by proctitis with eosinophil infiltrate of the rectal mucosa. A reduced mucus gel layer can be considered a contributory factor in the pathogenesis of the constipation.

Histological and genetic studies in patients with bicuspid aortic valve and ascending aorta complications

OBJECTIVES Aneurysm diameter and growing rate does not represent a definite parameter for operation in bicuspid aortic valve (BAV), ascending aortic aneurysm and normal root patients. Thus, we investigated histological and immunohistochemical aspects of different segments of ascending aorta (precisely, aortic root without dilatation, aneurysmatic tubular portion, dissected ascending aorta) and genetic features of patients with BAV and ascending aorta complication (aneurysm or dissection). METHODS Aorta tissue samples of 24 BAV patients were examined. The patients comprised of 18 men and 6 women; the mean age was 54.2 ± 14.3 years. All patients underwent composite aortic root replacement (button Bentall operation). Multiple histological sections were prepared from each aortic specimen. The evaluated features included elastic fibre fragmentation, cystic medial change, smooth muscle cell necrosis, medial fibrosis, and the markers of medial apoptosis and the metalloproteinases. Furthermore, genetic risk factors were also investigated. RESULTS The same medial degenerative lesions in tissue samples of different aorta segments (precisely of aortic root without dilatation, and aneurysmatic ascending aorta portion) were observed. More significant associations between single nucleotide polymorphisms (-786T/C endothelial nitric oxide synthase enzyme, D/I angiotensin-converting enzyme, -1562C/T metalloproteinase-9 and -735C/T metalloproteinase-2) and aneurysm risk were detected in BAV patients than in controls. CONCLUSIONS Based on our histological and genetic data, we underline that a surgical approach in patients with BAV, ascending aortic aneurysm and normal root, should consider not only the diameter of the aneurysmatic aortic portion but also the histological features of the whole ascending aorta and the genetic risk profile.

Abnormalities of the umbilico-portal venous system in Down syndrome: A report of two new patients

Congenital anomalies of the umbilical and portal venous system are rare vascular malformations which are often associated with anomalies of the heart and gastrointestinal tract. Association with chromosomal disorders has been sporadically reported. We now report on two patients with trisomy 21 and congenital anomalies of the umbilico‐portal system. A male fetus showed absence of the intrahepatic portal vein (PV) and ductus venosus with a direct communication between portal sinus and inferior vena cava exhibiting an umbilicosystemic total shunt during the fetal life and a portosystemic total shunt after birth. A female infant showed absence of the intrahepatic PV and a total portocaval shunt. Both patients also had heart defects. As previously documented in other reports, our cases demonstrated that this association may be causally‐related to the chromosomal aberration. In addition, the umbilico‐portal venous system abnormalities seems to be the most frequent congenital vascular malformation in Down syndrome. A presumptive pathogenetic mechanism could be a trisomy 21‐related altered angiogenesis of the vitelloumbilical plexus.

Focus on the unique mechanisms involved in thoracic aortic aneurysm formation in bicuspid aortic valve versus tricuspid aortic valve patients: clinical implications of a pilot study

OBJECTIVES The involvement of different factors in the onset of thoracic aortic aneurysm (TAA) in patients with a bicuspid aortic valve (BAV) vs those with a tricuspid aortic valve (TAV) is well recognized. However, the molecular, genetic and cellular mechanisms driving TAA remain unclear. The aim of this study was to identify the different mechanisms involved in TAA development in patients with BAV vs TAV. METHODS Aorta specimens and DNA samples were collected from 24 BAV (18 men and 6 women; mean age: 54.2 ± 14.39 years) and 110 TAV (79 men and 31 women, mean age: 66 ± 9.8 years) patients. A control group of 128 subjects (61 men and 67 woman, mean age: 61.1 ± 5.8 years) was also enrolled. Histopathological and immunohistochemical analyses were performed, as well as genotyping of 10 polymorphisms. RESULTS In BAV-associated ascending aortas, significant severe plurifocal apoptosis of smooth muscle cells and matrix metalloproteinase-9 (MMP-9) amounts were detected. In contrast, TAV-associated ascending aortas were characterized by a significant severity of elastic fragmentation, cystic medial necrosis, medial fibrosis and inflammation. In addition, in BAV cases, the -1562TMMP-9 and -735TMMP-2 alleles represent independent risk factors for TAA. The effects of these genotypes combined with hypertension and smoking in BAV cases result in an increase in both the apoptosis (P = 0.0001) and levels of MMP-9 (P = 0.001). In TAV cases, the D angiotensin-converting enzyme and +896A Toll-like receptor-4 alleles seem to be the predictive factors for TAA risk. They, combined with hypertension and age, significantly increase both the microscopic lesions and inflammation. CONCLUSIONS Our data seem to suggest that TAA in BAV and TAV patients arises from different molecular, cellular and genetic mechanisms. They might help to identify the potential molecular and genetic biomarkers that are useful to detect BAV subjects at high TAA risk, to monitor and treat them differently from those with TAV, with approaches such as the complete removal of the ascending aorta, including the aortic root with or without dilatation.

Can the TLR-4-Mediated Signaling Pathway Be “A Key Inflammatory Promoter for Sporadic TAA”?

Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

Comparison of iodinated contrast media for the assessment of atherosclerotic plaque attenuation values by CT coronary angiography: observations in an ex vivo model

OBJECTIVE To compare the influence of different iodinated contrast media with several dilutions on plaque attenuation in an ex vivo coronary model studied by multislice CT coronary angiography. METHODS In six ex vivo left anterior descending coronary arteries immersed in oil, CT (slices/collimation 64×0.625 mm, temporal resolution 210 ms, pitch 0.2) was performed after intracoronary injection of a saline solution, and solutions of a dimeric isosmolar contrast medium (Iodixanol 320 mgI ml(-1)) and a monomeric high-iodinated contrast medium (Iomeprol 400 mgI ml(-1)) with dilutions of 1/80 (low concentration), 1/50 (medium concentration), 1/40 (high concentration) and 1/20 (very high concentration). Two radiologists drew regions of interest in the lumen and in calcified and non-calcified plaques for each solution. 29 cross-sections with non-calcified plaques and 32 cross-sections with calcified plaques were evaluated. RESULTS Both contrast media showed different attenuation values within lumen and plaque (p<0.0001). The correlation between lumen and non-calcified plaque values was good (Iodixanol r=0.793, Iomeprol r=0.647). Clustered medium- and high-concentration solutions showed similar plaque attenuation values, signal-to-noise ratios (SNRs) (non-calcified plaque: medium solution SNR 31.3±15 vs 31.4±20, high solution SNR 39.4±17 vs 37.4±22; calcified plaque: medium solution SNR 305.2±133 vs 298.8±132, high solution SNR 323.9±138 vs 293±123) and derived contrast-to-noise ratios (p>0.05). CONCLUSION Differently iodinated contrast media have a similar influence on plaque attenuation profiles. ADVANCES IN KNOWLEDGE Since iodine load affects coronary plaque attenuation linearly, different contrast media may be equally employed for coronary atherosclerotic plaque imaging.

Noncompaction of the Right Ventricle

Noncompaction of the ventricular myocardium is a disease characterized by an increase of the ventricular trabecular meshwork caused by arrest of the normal endomyocardial morphogenesis (Figs. 1, 2, 3). In accordance with the normal human anatomy, the left ventricular wall is well compacted with a few thin trabeculae; on the contrary, the normal right ventricular wall is furrowed by many trabeculae (the trabecula of the marginal septum as well as other ones). For this reason, the term ‘‘noncompaction’’ usually refers to an exclusive or prevalent disease of the left ventricle [1–16]. Recently Song and Aragona et al. [1–3] reported two cases of isolated right-ventricular noncompaction. According to the data coming from scientific literature and from our own experience, in some patients noncompaction is biventricular [5, 6], and an increase of the right ventricular meshwork is often evident in such cases, even more so than on the left side. The main diagnostic criterion of noncompaction, that is, the only one that is accepted and recognized, is evaluation of the ratio between the spongiosus and the compact thickness of the ventricular wall, which must be [2 [6–16]. This ratio is easy to calculate for the left ventricle; on the contrary, it is more difficult to calculate for the right ventricle. Only one case of right-ventricular noncompaction has been reported in the literature [7, 8]. In our personal clinical experience, we have found that many cases of biventricular noncompaction are reported in the register of Italian Society of Cardiovascular Echocardiography. Recently two patients with an inexplicable dilatation of the right ventricle caught our attention: Both of them showed a more prominent trabecular meshwork on

Sudden death in adolescence caused by cardiac haemangioma

Primary tumors of the heart in infants and children are rare. The types of heart tumors in pediatric age groups are generally different from those in adults. Cardiac myxoma is by far the most common tumor in adults, but in infants and adolescents the prevalent tumor of the heart is rhabdomyoma. Among benign cardiac tumors, cardiac hemangiomas are rare and often diagnosed post-mortem due to the lack of specific clinical symptoms and signs. We report a case of sudden death due to cardiac hemangioma in an apparently healthy 15-year-old adolescent. The autopsy revealed a cardiac hemangioma located at the apex of the heart; the histopathological examination showed the tumor was a mixed capillary and arteriolar hemangioma, a very rare type of primary tumor in adolescents.

Oligo-Antigenic Diet in the Treatment of Chronic Anal Fissures. Evidence for a Relationship Between Food Hypersensitivity and Anal Fissures

OBJECTIVES:Patients with chronic constipation due to food hypersensitivity (FH) had an elevated anal sphincter resting pressure. No studies have investigated a possible role of FH in anal fissures (AFs). We aimed to evaluate (1) the effectiveness of diet in curing AFs and to evaluate (2) the clinical effects of a double-blind placebo-controlled (DBPC) challenge, using cows milk protein or wheat.METHODS:One hundred and sixty-one patients with AFs were randomized to receive a “true-elimination diet” or a “sham-elimination diet” for 8 weeks; both groups also received topical nifedipine and lidocaine. Sixty patients who were cured with the “true-elimination diet” underwent DBPC challenge in which cows milk and wheat were used.RESULTS:At the end of the study, 69% of the “true-diet group” and 45% of the “sham-diet group” showed complete healing of AFs (P<0.0002). Thirteen of the 60 patients had AF recurrence during the 2-week cows milk DBPC challenge and 7 patients had AF recurrence on wheat challenge. At the end of the challenge, anal sphincter resting pressure significantly increased in the patients who showed AF reappearance (P<0.0001), compared with the baseline values. The patients who reacted to the challenges had a significantly higher number of eosinophils in the lamina propria and intraepithelial lymphocytes than those who did not react to the challenges.CONCLUSIONS:An oligo-antigenic diet combined with medical treatment improved the rate of chronic AF healing. In more than 20% of the patients receiving medical and dietary treatment, AFs recurred on DBPC food challenge.

A particular phenotype of ascending aorta aneurysms as precursor of type A aortic dissection

OBJECTIVES We aimed to identify a phenotype of ascending thoracic aortic aneurysm (TAA), which, more than others, evolves into type A dissection (TAD). METHODS Aortic specimens were obtained from patients undergoing surgical repair of TAA and TAD (108 and 26, respectively). Histopathological and immunohistochemical analyses were performed by using adequate tissue specimens, appropriate techniques and criteria. RESULTS We identified the three following TAA phenotypes: phenotype I (cystic medial degeneration balanced by a substitutive fibrosis, in absence of medial apoptosis and with a faint collagenase concentration), phenotype II (cystic medial degeneration of higher grade, respectively, than substitutive fibrosis, with focal medial apoptosis and moderate collagenase concentration), and phenotype III (elevated cystic medial degeneration without substitutive fibrosis, with plurifocal medial apoptosis and severe collagenase concentration). The same medial degenerative lesions of TAA phenotype III were observed in TAD tissue samples. CONCLUSIONS The morphological identity of medial lesions observed in both the TAA phenotype III and in TAD aortas might be assumed to be the precursor-and consequently the optimal biomarker- of dissection, independently of aneurysm diameter or valvular disorder. Identification of genetic risk factors, useful both in diagnostics and in developing more targeted treatment for individual patients, might also be needed.