Journal of Pediatric Gastroenterology and Nutrition, 1990
Protein-losing enteropathy (PLE) and edema are usually the most prominent clinical features in ch... more Protein-losing enteropathy (PLE) and edema are usually the most prominent clinical features in children with Ménétrier's disease. However, the changes in gastrointestinal mucosa that can cause PLE have not been described yet in children. We studied by electron microscopy the mucosa of the gastric fundus, which is the site where macroscopic changes are most prominent, in two children with Ménétrier's disease. We found that tight junction width was increased to 10.5 +/- 0.94 nm (mean +/- 1 SD) in one child and to 9.7 +/- 0.7 in the other. Tight junction width returned to normal when PLE and edema subsided. These ultrastructural changes were similar to those described in adults with the disease, although the clinical course of Ménétrier's disease is very different in adults and in children. Both patients showed evidence of cytomegalovirus (CMV) infection, as indicated by increasing IgG antibodies against the virus or recovery of the virus in the urine. Although Helicobacter pylori was found in the antral mucosa of one patient, the clinical course of the disease was not related to this microorganism. We conclude that increased tight junction width plays a role in PLE seen in Ménétrier's disease in children and that CMV, rather than Helicobacter pylori, is associated with the disease.
RATIONALE Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but ... more RATIONALE Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. OBJECTIVES To investigate evolution of static lung volumes with ultrastructural defects, gene mutations, BMI, and specific infections in PCD. METHODS Prospective, longitudinal, single-center study in children and adults evaluated twice yearly for up to 10 years. Linear mixed effects models were used to assess associations between ciliary morphology, genetic mutations, and clinical features. RESULTS 122 patients had 1096 visits. At enrollment, almost all spirometric and, especially in adults, plethysmographic parameters were significantly worse in absent inner dynein arms, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) compared with Normal Electron Microscopy (EM) patients. Mean trend increase with time for residual volume (RV) was significantly higher in IDA/CA/MTD compared to outer dynein arms (ODA) defect an...
Cilia have multiple functions including olfaction. We hypothesised that olfactory function could ... more Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.
International journal of immunopathology and pharmacology
The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrela... more The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrelated to cystic fibrosis or primary ciliary dyskinesia. In 51 children with recurrent pneumonia, high resolution computed tomography (HRCT) was carried out to detect and score bronchiectasis. Moreover, ciliary ultrastructure, beat frequency and motion pattern were evaluated and compared to those observed in 30 healthy children. Bronchiectasis at HRCT was found in 31/51 children. Ciliary dysmotility was found in 20/31 children with bronchiectasis (64.5%). Overall, ciliary dysmotility was found in 39/51 patients (76.5%). Ciliary dysmotility showed a significant correlation with the HRCT score (p=0.02). Absent motion in some fields was found in 44/51 patients (86.3%) and this also showed significant correlation with the HRCT score (p=0.005). The specificity and sensitivity of ciliary dysmotility as an indicator of bronchiectasis was 74.3% and 83.3% respectively. The positive predictive value ...
Virchows Archiv : an international journal of pathology, 2006
Microvillous Inclusion Disease (MID) is an inherited disorder characterized by intractable diarrh... more Microvillous Inclusion Disease (MID) is an inherited disorder characterized by intractable diarrhea in infancy. Ultrastructural detection of pathognomonic microvillous inclusions in the enterocytes is essential for diagnosis. The aim of this research is to contribute to the knowledge of MID studying enterocytes and goblet cells (gc). Samples of duodenal mucosa from two young infants with MID (aged 75 days and 3 months, respectively) were studied by light and electron microscopy. Detection in the intestinal villi of immature gc (with microvilli) in one of the cases led us to seek them in control samples. The total number of gc with microvilli (immature) and without microvilli (mature) were counted. In both MID specimens, light microscopy showed atrophy of villi and PAS-positive material in the enterocyte cytoplasm. The ultrastructure of villous enterocytes was characterized by brush-border abnormalities, microvillous inclusions, dense apical granules, and lysosomes. Intermediate stru...
Minerva urologica e nefrologica = The Italian journal of urology and nephrology, 1996
Percutaneous renal biopsies were performed on native kidneys in 40 children and adolescent, aged ... more Percutaneous renal biopsies were performed on native kidneys in 40 children and adolescent, aged 1.7-13 (mean 6.7) years. Bleeding diatheses were excluded by the determination of Hb, blood platelets, PT, PTI and fibrinogen. Biopsies were performed under ultrasound imaging, using a semiautomated and thin needle (20 gauge in children with age under 5 years and 18 gauge for those over 5 years). All the patients were lightly sedated, except for 3 ones who received a general anesthesia. Diagnostically adequate tissue was retrieved in 38 of 40 biopsy procedures (95%). A macro-haematuria was observed with elimination of haematic coagula in 3 children (7.5%) and 24-h post-biopsy ultrasonography disciosed a small haematoma of the biopsied kidney in 2 one (5%). No mayor complications occurred. We conclude that the use of ultrasound imaging and a semiautomated needle is a safe and efficient method for performing renal biopsies in paediatric patients. The use of smaller (18 or 20-gauge) cutting...
The aim of the study was to assess Torquetenovirus (TTV) loads within respiratory ciliated cells ... more The aim of the study was to assess Torquetenovirus (TTV) loads within respiratory ciliated cells and to verify the existence of a correlation between TTV loads and functional or structural ciliary abnormalities, in a group of children with recurrent or persistent pneumonia. Nasal brushing samples of 55 children (28 male) were evaluated for ciliary motion and ultrastructural assessment, as well as for detection and quantification of TTV. Moreover, presence and load of TTV within ciliated cells, obtained from 5 patients by laser capture microdissection, were determined. The nasal samples of 47 (85%) children with persistent or recurrent pneumonia resulted positive for TTV (loads = 2.1-7.3 log10 copies/microg total DNA). TTV were demonstrated also within microdissected ciliated cells. No significant difference between primary (11 subjects) and secondary ciliary dyskinesia (44 subjects) for TTV prevalence and mean loads were found. A significant correlation was observed between nasal TTV loads and ciliary beat frequency score (r = 0.305; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), but not between TTV loads and presence of abnormal motion patterns, in patients with secondary ciliary abnormalities. As expected no correlations were found between nasal TTV loads and ciliary motion analysis in primary ciliary dyskinesia. The presence of TTV in nasal samples demonstrates TTV ability to infect respiratory ciliated cells and suggests that these cells are potentially able to support virus replication. Moreover, TTV may behave in respiratory cells in a similar way to other viruses, that is, they disrupt the mucociliary escalator.
Ribosome-lamella complexes (RLCs) are mainly observed in a variety of hematological disorders and... more Ribosome-lamella complexes (RLCs) are mainly observed in a variety of hematological disorders and occasionally in solid neoplasms and in nonneoplastic diseases. These intracytoplasmic organelles are held to arise from rough endoplasmic reticulum, but, in agreement with more recent literature data, their function is still unclear. Ultrastructural analysis of glomeruli from a patient with focal segmental glomerulosclerosis secondary to metabolic syndrome disclosed significant foot process loss and abundant cytoskeletal proteins in major podocyte processes; two of the latter also displayed RLCs. This is the second report of RLCs in human renal glomerulus. Their close association with cytoskeletal proteins and lysosomes suggests a relationship with abnormal protein biosynthesis.
Journal of Pediatric Gastroenterology and Nutrition, 1990
Protein-losing enteropathy (PLE) and edema are usually the most prominent clinical features in ch... more Protein-losing enteropathy (PLE) and edema are usually the most prominent clinical features in children with Ménétrier&#39;s disease. However, the changes in gastrointestinal mucosa that can cause PLE have not been described yet in children. We studied by electron microscopy the mucosa of the gastric fundus, which is the site where macroscopic changes are most prominent, in two children with Ménétrier&#39;s disease. We found that tight junction width was increased to 10.5 +/- 0.94 nm (mean +/- 1 SD) in one child and to 9.7 +/- 0.7 in the other. Tight junction width returned to normal when PLE and edema subsided. These ultrastructural changes were similar to those described in adults with the disease, although the clinical course of Ménétrier&#39;s disease is very different in adults and in children. Both patients showed evidence of cytomegalovirus (CMV) infection, as indicated by increasing IgG antibodies against the virus or recovery of the virus in the urine. Although Helicobacter pylori was found in the antral mucosa of one patient, the clinical course of the disease was not related to this microorganism. We conclude that increased tight junction width plays a role in PLE seen in Ménétrier&#39;s disease in children and that CMV, rather than Helicobacter pylori, is associated with the disease.
RATIONALE Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but ... more RATIONALE Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. OBJECTIVES To investigate evolution of static lung volumes with ultrastructural defects, gene mutations, BMI, and specific infections in PCD. METHODS Prospective, longitudinal, single-center study in children and adults evaluated twice yearly for up to 10 years. Linear mixed effects models were used to assess associations between ciliary morphology, genetic mutations, and clinical features. RESULTS 122 patients had 1096 visits. At enrollment, almost all spirometric and, especially in adults, plethysmographic parameters were significantly worse in absent inner dynein arms, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) compared with Normal Electron Microscopy (EM) patients. Mean trend increase with time for residual volume (RV) was significantly higher in IDA/CA/MTD compared to outer dynein arms (ODA) defect an...
Cilia have multiple functions including olfaction. We hypothesised that olfactory function could ... more Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.
International journal of immunopathology and pharmacology
The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrela... more The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrelated to cystic fibrosis or primary ciliary dyskinesia. In 51 children with recurrent pneumonia, high resolution computed tomography (HRCT) was carried out to detect and score bronchiectasis. Moreover, ciliary ultrastructure, beat frequency and motion pattern were evaluated and compared to those observed in 30 healthy children. Bronchiectasis at HRCT was found in 31/51 children. Ciliary dysmotility was found in 20/31 children with bronchiectasis (64.5%). Overall, ciliary dysmotility was found in 39/51 patients (76.5%). Ciliary dysmotility showed a significant correlation with the HRCT score (p=0.02). Absent motion in some fields was found in 44/51 patients (86.3%) and this also showed significant correlation with the HRCT score (p=0.005). The specificity and sensitivity of ciliary dysmotility as an indicator of bronchiectasis was 74.3% and 83.3% respectively. The positive predictive value ...
Virchows Archiv : an international journal of pathology, 2006
Microvillous Inclusion Disease (MID) is an inherited disorder characterized by intractable diarrh... more Microvillous Inclusion Disease (MID) is an inherited disorder characterized by intractable diarrhea in infancy. Ultrastructural detection of pathognomonic microvillous inclusions in the enterocytes is essential for diagnosis. The aim of this research is to contribute to the knowledge of MID studying enterocytes and goblet cells (gc). Samples of duodenal mucosa from two young infants with MID (aged 75 days and 3 months, respectively) were studied by light and electron microscopy. Detection in the intestinal villi of immature gc (with microvilli) in one of the cases led us to seek them in control samples. The total number of gc with microvilli (immature) and without microvilli (mature) were counted. In both MID specimens, light microscopy showed atrophy of villi and PAS-positive material in the enterocyte cytoplasm. The ultrastructure of villous enterocytes was characterized by brush-border abnormalities, microvillous inclusions, dense apical granules, and lysosomes. Intermediate stru...
Minerva urologica e nefrologica = The Italian journal of urology and nephrology, 1996
Percutaneous renal biopsies were performed on native kidneys in 40 children and adolescent, aged ... more Percutaneous renal biopsies were performed on native kidneys in 40 children and adolescent, aged 1.7-13 (mean 6.7) years. Bleeding diatheses were excluded by the determination of Hb, blood platelets, PT, PTI and fibrinogen. Biopsies were performed under ultrasound imaging, using a semiautomated and thin needle (20 gauge in children with age under 5 years and 18 gauge for those over 5 years). All the patients were lightly sedated, except for 3 ones who received a general anesthesia. Diagnostically adequate tissue was retrieved in 38 of 40 biopsy procedures (95%). A macro-haematuria was observed with elimination of haematic coagula in 3 children (7.5%) and 24-h post-biopsy ultrasonography disciosed a small haematoma of the biopsied kidney in 2 one (5%). No mayor complications occurred. We conclude that the use of ultrasound imaging and a semiautomated needle is a safe and efficient method for performing renal biopsies in paediatric patients. The use of smaller (18 or 20-gauge) cutting...
The aim of the study was to assess Torquetenovirus (TTV) loads within respiratory ciliated cells ... more The aim of the study was to assess Torquetenovirus (TTV) loads within respiratory ciliated cells and to verify the existence of a correlation between TTV loads and functional or structural ciliary abnormalities, in a group of children with recurrent or persistent pneumonia. Nasal brushing samples of 55 children (28 male) were evaluated for ciliary motion and ultrastructural assessment, as well as for detection and quantification of TTV. Moreover, presence and load of TTV within ciliated cells, obtained from 5 patients by laser capture microdissection, were determined. The nasal samples of 47 (85%) children with persistent or recurrent pneumonia resulted positive for TTV (loads = 2.1-7.3 log10 copies/microg total DNA). TTV were demonstrated also within microdissected ciliated cells. No significant difference between primary (11 subjects) and secondary ciliary dyskinesia (44 subjects) for TTV prevalence and mean loads were found. A significant correlation was observed between nasal TTV loads and ciliary beat frequency score (r = 0.305; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), but not between TTV loads and presence of abnormal motion patterns, in patients with secondary ciliary abnormalities. As expected no correlations were found between nasal TTV loads and ciliary motion analysis in primary ciliary dyskinesia. The presence of TTV in nasal samples demonstrates TTV ability to infect respiratory ciliated cells and suggests that these cells are potentially able to support virus replication. Moreover, TTV may behave in respiratory cells in a similar way to other viruses, that is, they disrupt the mucociliary escalator.
Ribosome-lamella complexes (RLCs) are mainly observed in a variety of hematological disorders and... more Ribosome-lamella complexes (RLCs) are mainly observed in a variety of hematological disorders and occasionally in solid neoplasms and in nonneoplastic diseases. These intracytoplasmic organelles are held to arise from rough endoplasmic reticulum, but, in agreement with more recent literature data, their function is still unclear. Ultrastructural analysis of glomeruli from a patient with focal segmental glomerulosclerosis secondary to metabolic syndrome disclosed significant foot process loss and abundant cytoskeletal proteins in major podocyte processes; two of the latter also displayed RLCs. This is the second report of RLCs in human renal glomerulus. Their close association with cytoskeletal proteins and lysosomes suggests a relationship with abnormal protein biosynthesis.
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Papers by Angela Cangiotti