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Glycogenosis type II or Pompe disease is an inherited autosomal recessive disorder known in 3 different clinical forms (infantile, juvenile and adult). We report on a case diagnosed as a classic infantile form with the worst outcome of all 3 described, if we had followed and executed a correct and complete diagnostic pathway. A 7 months old female child was admitted for fever and dyspnoea. At chest auscultation weepings and weezings were found; on the cardiac apex a murmur due to mitralic failure was retrieved. The thorax X-ray showed a greatly increased heart shadow with a cardiothoracic index of 0.75. ECG showed high voltages and signs of bilateral ventricular hypertrophy. Cardiac ultrasonography confirmed the presence of a big heart with an enormous swollen left ventricle and a severe mitralic failure. The clinical diagnosis of infantile Pompe disease was confirmed by the almost total absence of cellular acid a-glucosidase activity but we couldn't perform the assay because of the rapid exitus of our patient, which occurred before glycogen storage disease II was suspected. So, we tried to compare our case with others reported in the literature in order to ratify our diagnostic hypothesis. The contribution of genetic counseling practiced on all the couples at risk remains useful every time that a certain diagnosis is made.

BACKGROUND: Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown. AIMS: To evaluate the histology and manometry pattern in patients with food intolerance-related constipation. PATIENTS AND METHODS: Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry. RESULTS: A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucus than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation.

OBJECTIVE: Chronic constipation in children can be linked to cow''s 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 cow''s 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.

Aging has a striking impact on the heart and the vascular system, particularly on the large elastic arteries (i.e., aorta), resulting in a multitude of changes at different structural and functional levels. As result, medial degeneration (MD) occurs. A characteristic example of MD is sporadic thoracic aortic aneurysm (S-TAA), whose patho-physiological mechanisms remain unclear. In this study, typical MD morphological phenotypes were researched in S-TAA cases and control aorta specimens by histopathological and immunohistochemical analyses. Three phenotypes (I, II, and III) were detected, but mainly the phenotype III was observed. Elevated cystic MD, plurifocal medial apoptosis, and increased metalloproteinase-9 amount characterize it. In addition, it was significantly correlated with the severity of elastic fragmentation, hypertension, and smoking, and particularly with advancing age. Thus, phenotype III might represent the typical MD phenotype associated with S-TAA in old people that have a major risk of aorta rupture and dissection independently on aneurysm diameter. This might permit the assumption that phenotype III with its typical histological abnormalities is an optimal biomarker of rupture and/or dissection in aged individuals and is useful both for applying different surgical approaches and providing appropriate surgical indications

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.

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 cow's 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 cow's 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

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 immunoistochemical 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.

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.

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.

Oral lichen planus (OLP) is an autoimmune disease with an inflammatory pathogenesis. The angiogenetic phenomenon is a mechanism at the base of the pathogenesis of chronic inflammatory processes. The aim of this research is to evaluate the angiogenetic phenomenon, comparing an in vitro method with an in vivo one. Thirty OLP patients and 30 healthy subjects were enrolled in the study. Immunohistochemical analysis of the vascular-endothelial growth factor (VEGF) and vascular-endothelial adhesion molecules were carried out by the means of primary antibodies and anti-CD34, anti-VEGF, anti-CD106 antigen (VCAM-1) and anti-CD54 antigen (ICAM-1). Capillary density and others capillaroscopic parameters were tested in vivo using oral videocapillaroscopy. The results reveal the presence of a significant angiogenesis in OLP patients through the immunoexpression of VEGF, CD34, CD106 and CD54 (p

Objective: Oral Lichen Planus (OLP) is a chronic inflammatory disease with an autoimmune inflammatory pathogenesis. The aim of the research is to compare the vascular endothelial growth factor (VEGF) and adhesion of molecules in the biopsy samples of patients affected by OLP, in order to research the presence of the angiogenetic phenomenon and to understand its pathogenetic mechanism. Materials and Methods: Thirty OLP patients and thirty healthy subjects were enrolled in a study. The immunohistochemical analysis of the VEGF and vascularendothelial adhesion molecules was carried out by means of primary antibodies and anti-CD34, anti-VEGF, antiCD106 antigen (VCAM-1) and anti-CD54 antigen (ICAM-1). The statistical significance of the differences was checked with the Mann-Whitney test (MW test). The level of significance was set to P

Hemangiopericytoma (HPC) is a mesenchymal tumour that may be benign, malignant, or occur in an intermediate form. We report an unusual case of hemangiopericytoma located in the buccal mucosal region. The histopathologic features showed increased cellularity, necrosis, hemorrhage, low proliferation index, and 4 or less mitotic figures per 10 high-power fields. Since this histological pattern suggests an intermediate form characterized by unpredictable clinical behavior, life-long follow-up is essential. In this patient no recurrences or distant metastases were evident at 10-yr follow-up.

The main aims of this cross-sectional study were: (i) to assess the frequency of genital (vulval) lichen planus (VLP) and vulval lichen sclerosus (VLS) in women affected with oral lichen planus (OLP), regardless of the genital symptoms reported; and (ii) to verify whether any demographic, clinical, or histological features of OLP are associated with a higher risk of vulvo-vaginal involvement. Fifty-five women, presenting OLP, consecutively underwent gynaecological examination and, if they demonstrated positive clinical signs of VLP, underwent biopsy. After a drop-out of 14 subjects, 31/41 (75.6%) were found to have signs of genital involvement, of which 13/31 (44.0%) were asymptomatic. Following genital biopsy, 27/31 (87.1%) had histologically confirmed VLP or VLS. Following both univariate and multivariate statistical analyses, no significant association was found between gynaecological concomitance and demographic, clinical, histological features of OLP. This unpredictably common genital involvement in females with OLP emphasizes the importance of routinely performing both oral and gynaecological examinations, to facilitate an early and correct therapeutic approach. © 2006 Acta Dermato-Venereologica.

The aim of our 10-year study was to test the effectiveness of topical therapy based on 0. 18% isotretinoin, comparing it with that most frequently used, i.e. at 0.05% concentration. Seventy patients with an established diagnosis of oral lichen planus were involved in the study. The patients were randomly divided into two groups, and the drug was administered topically at 0.05% and 0. 18% concentrations. The drug at the higher concentration, according to the same protocol, was administered to the patients who did not benefit from the therapy at the lower concentration. None of the cases of reticular lichen planus showed clinical or histological improvement. In contrast, the atrophic-erosive forms showed a significant improvement, both clinical and histological: in 26 patients (at 0.18% concentration) and in nine patients (at 0.05% concentration), the symptoms, as well as the erosions or ulcers observed, disappeared. The disappearance of dysplasic phenomena was observed at 0. 18% concentration. Topical application of the drug was accompanied by an increase in soreness and pain, as well as greater sensitivity to hot foods. However, these side effects were transitory, and considered acceptable by the patients. The proposed therapeutic protocol was effective towards highly active atrophic-erosive oral lichen planus with dysplasic phenomena, which is the form of the disease at higher risk of malignant evolution.

A newborn with an unusual association of hepatic mesenchymal hamartoma and mesenchymal stem villous hyperplasia of the placenta is presented. At birth, the large hepatic mass caused severe respiratory distress necessitating early surgical intervention. This report on the association of hepatic mesenchymal hamartoma and mesenchymal stem villous hyperplasia of the placenta strongly suggests a common pathogenetic origin of the 2 lesions.

Various studies have evaluated the therapeutic effectiveness of vitamin A derivatives in the treatment of oral leukoplakia (OL). Not all the studies have shown concordant results. The aim of our study, which has a 10-year follow-up, was to test the effectiveness of topical therapy based on 0.18% isotretinoin by comparing it with that most frequently used, i.e., at 0.05% concentration. Forty patients with an established diagnosis of OL were involved in the study. The patients were randomly divided into two groups and the drug was administered topically at 0.05% and 0.18% concentrations. The drug was applied twice a day for 3 consecutive months; then it was suspended for 1 month, and the biopsy sample was repeated for the histological follow-up. The higher concentration of the drug, according to the same protocol, was administered to patients who did not benefit from the lower concentration. The results showed a significant reduction in lesions (85%), with no documented topical or systemic adverse reactions at 0.18% concentration. A significant reduction of the aggressiveness of the disease and the disappearance of dysplastic phenomena were observed histologically. The proposed therapeutic protocol was effective toward highly active oral leukoplakia with dysplastic phenomena, and therefore at higher risk of malignant progression.

The aim of this report was to evaluate the effectiveness of the endoscopic treatment of colonic polyps to allow secondary prophylaxis in order to prevent the onset of cancer arising from adenomas. From October 2002 to January 2004 we performed 487 colonoscopies on a patient group with the following indications: screening prior to kidney transplant; screening for colorectal cancer (patients positive at faecal occult blood testing); follow-up of patients who had undergone colonic resections for colorectal cancer; patients with other diseases. Colorectal polyps were diagnosed in 15 males and 15 females, with a mean age of 63 years. All the neoplasms were resected during colonoscopy and specimens sent for histological study. The histological examinations yielded the following results: 4 hyperplastic polyps; 9 tubular adenomas (6 with mild, 2 with mild-to-moderate, and 1 with severe dysplasia); 8 tubulo-villous adenomas (3 with mild, 1 with mild-to-moderate, and 4 with moderate dysplasia); 4 villous adenomas (3 with mild and 1 with severe dysplasia); 1 adenocarcinoma; 1 inflammatory polyp; in 3 cases we were unable to retrieve the polyps after polypectomy. Colonoscopic detection of a neoplasm allows us to remove it and send to the pathology laboratory for definitive histological diagnosis. Moreover, snare polypectomy can be a radical treatment for dysplastic polyps without stromal axis and basal membrane infiltration. We therefore conclude that colonoscopy allows not only early diagnosis of colonic neoplasms, but also radical curative treatment in the early stages. The aim of this report was to evaluate the effectiveness of the endoscopic treatment of colonic polyps to allow secondary prophylaxis in order to prevent the onset of cancer arising from adenomas. From October 2002 to January 2004 we performed 487 colonoscopies on a patient group with the following indications: screening prior to kidney transplant; screening for colorectal cancer (patients positive at faecal occult blood testing); follow-up of patients who had undergone colonic resections for colorectal cancer; patients with other diseases. Colorectal polyps were diagnosed in 15 males and 15 females, with a mean age of 63 years. All the neoplasms were resected during colonoscopy and specimens sent for histological study. The histological examinations yielded the following results: 4 hyperplastic polyps; 9 tubular adenomas (6 with mild, 2 with mild-to-moderate, and 1 with severe dysplasia); 8 tubulo-villous adenomas (3 with mild, 1 with mild-to-moderate, and 4 with moderate dysplasia); 4 villous adenomas (3 with mild and 1 with severe dysplasia); 1 adenocarcinoma; 1 inflammatory polyp; in 3 cases we were unable to retrieve the polyps after polypectomy. Colonoscopic detection of a neoplasm allows us to remove it and send to the pathology laboratory for definitive histological diagnosis. Moreover, snare polypectomy can be a radical treatment for dysplastic polyps without stromal axis and basal membrane infiltration. We therefore conclude that colonoscopy allows not only early diagnosis of colonic neoplasms, but also radical curative treatment in the early stages.