Eradication of JAK2 V617F mutation after allogeneic transplantation in a patient with myelofibrosis with myeloid metaplasia.
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Hematopoietic Stem Cell Transplantation↗
Biomedical subjects
A Fiorini
Publications and source records attributed to A Fiorini.
Screening of JAK2 V617F mutation in multiple myeloma.
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Genetic Testing↗
Scaffold/Matrix Attachment Regions and intrinsic DNA curvature.
Recent approaches have failed to detect nucleotide sequence motifs in Scaffold/Matrix Attachment Regions (S/MARs). The lack of any known motifs, together with the confirmation that some S/MARs are not associated to any peculiar sequence, indicates that some structural elements, such as DNA curvature, have a role in chromatin organization and on their efficiency in protein binding. Similar to DNA curvature, S/MARs are located close to promoters, replication origins, and multiple nuclear processes like recombination and breakpoint sites. The chromatin structure in these regulatory regions is important to chromosome organization for accurate regulation of nuclear processes. In this article we review the biological importance of the co-localization between bent DNA sites and S/MARs.
Animals↗
Imatinib for secondary Ph+ acute lymphoblastic leukemia induces response in concomitant GBM.
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Adult↗
[Hepato-pulmonary syndrome and porto-pulmonary hypertension. Nosologic features and etiopathogenic considerations].
The liver controls pulmonary vascular tone by releasing vasoactive substances. In severe liver failure, the imbalance between vasodilator and vasoconstrictive mediators may lead to alteration of the respiratory function, called as hepatopulmonary syndrome (HPS, when a significant decrease of the vascular pulmonary resistance occurs, with development of intrapulmonary vascular dilatations) and portopulmonarv hypertension (PPH, when the vasoconstrictive prevalence, with an increase of the pulmonary vascular resistances). The clinical symptoms consist of various degree of dyspnea and hypoxemia. An overt "cor pulmonale" syndrome with right-side heart failure may be present in the most severe forms of PPH. The alteration of pulmonary vascularization may be diagnosed by means of pulmonary angiography, contrast-enhanced echocardiography and perfusion lung nuclear scanning of the lungs. Both clinical syndromes respond poorly to medical treatment, the unique therapeutical possibilities being represented by orthotopic liver transplantation (or combined heart-lung-liver or lung-liver transplantation in patients with severe PPH).
Hepatopulmonary Syndrome↗
Self-expandable metal coil stents in the treatment of benign esophageal strictures refractory to conventional therapy: a case series.
BACKGROUND: Benign, refractory esophageal strictures are an important therapeutic challenge. Metallic self-expandable stents developed to treat malignant strictures have occasionally been used in the treatment of benign stenoses. This is a report of the use of 14 esophageal metallic stents in 10 patients with severe benign strictures. METHODS: Ten patients with peptic, post-surgical, or post-radiation esophageal strictures were treated with metallic stents. All patients had previously been treated, unsuccessfully, by endoscopic dilatation. Their strictures, although benign, gave rise to the same problems as malignant ones. RESULTS: In all patients, marked improvement of dysphagia was achieved with the use of metallic stents. They were inserted without early complications except for chest pain in one patient. Late complications were proximal and distal migration (in three patients) and a proximal stricture in one other patient. The best results were achieved in post-radiation strictures. CONCLUSIONS: Metallic stents can be considered as a therapeutic alternative in selected patients with severe benign esophageal strictures refractory to conventional treatment.
Aged↗
The natural history of gluten sensitivity: report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives.
OBJECTIVE: Early studies revealed that up to 50% of non-atrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment. METHODS: After a median time of 86 months (range: 42-102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy. RESULTS: At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype. CONCLUSIONS: Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.
Adolescent↗
Characterization of gastric mucosal lesions in patients with celiac disease: a prospective controlled study.
OBJECTIVE: Several studies have demonstrated that chronic exposure to gluten may damage the structure and function of the gastric mucosa in gluten-sensitive patients. However, until now, these abnormalities have been incompletely studied. Our purpose in the present study was to characterize, in a prospective controlled study, the endoscopic and histological appearance of the gastric mucosa in a large cohort of patients with celiac disease with and without Helicobacter pylori (H. pylori) infection. METHODS: We evaluated biopsy specimens taken from the gastric body and antrum of 218 individuals who underwent upper endoscopy for small bowel biopsy. One hundred-four patients had celiac disease (80 of them at the time of diagnosis-untreated). In 114 subjects celiac disease was excluded. RESULTS: Endoscopic findings did not show a difference between the groups. The prevalence of cases with normal gastric mucosa, chronic superficial gastritis, and atrophic gastritis was similar in patients and controls. Similarly, presence of metaplasia, inflammatory activity, and lymphoid follicles and aggregates did not show differences between the groups. Histological or serological evidence of H. pylori infection was detected in 86% of patients (82% of untreated celiacs and 95% of those on those taking treatment). The infection was highly prevalent in patients (89%) and controls (97%) diagnosed with chronic gastritis. Untreated patients had a significant greater IEL count in the antrum and corpus than controls (p < 0.0001 and p < 0.001, respectively). A global analysis of the data on intraepithelial lymphocyte (IEL) counts in the different populations suggest that the inflammatory state may represent the cumulative effect of H. pylori infection and gluten sensitivity. Only three patients had IEL infiltration compatible with diagnosis of lymphocytic gastritis (count >25%) and three other patients had borderline counts. CONCLUSIONS: According to our results, celiac disease patients presented a similar prevalence of gastric mucosal abnormalities compared with the control population. Evidence of H. pylori infection was very high compared with the prevalence in the general Argentine population. As a particular observation in our celiac population, the disease was rarely associated with lymphocytic gastritis. We suggest that the chronic inflammatory state evidenced by a gastric mucosal lymphocyte infiltration may be secondary to the combination of H. pylori infection and chronic gluten ingestion in gluten-sensitive subjects.
Adolescent↗
Sugar tests detect celiac disease among first-degree relatives.
OBJECTIVES: First-degree relatives of patients with celiac disease are at high risk for developing the disease themselves. Detection of serum antibodies and intestinal permeability tests have been useful to identify candidates for intestinal biopsies. Recently it was demonstrated that abnormal sucrose permeability is a very sensitive marker of active disease. Our objectives in this prospective study were (1) to assess the screening value of permeability tests, and (2) to compare the usefulness of these markers with that of the celiac disease-related serology in screening for celiac disease in a cohort of first-degree relatives of well-known patients. METHODS: We performed sugar tests in 66 first-degree relatives of probands. Subjects ingested 450 ml of a solution containing sucrose (100 g), lactulose (5 g), and mannitol (2 g). Subsequently, a complete overnight urine collection was obtained. Measurement of sugars was performed by high-performance liquid chromatography. All relatives were evaluated for antigliadin (type IgA and IgG) and endomysial antibodies and subjects positive for any test underwent intestinal biopsy. RESULTS: Twelve relatives were diagnosed as having small intestinal mucosal atrophy. Increased sucrose permeability was detected in 9 (75%) of these patients. Four false-positive determinations were found but all had gastric erosions, which is known to increase sucrose permeability independently of duodenal damage. Increased lactulose/mannitol ratios were observed in all new celiac patients. An additional nine relatives had positive results; however, four of them did not accept intestinal biopsy and the remaining five did not seem to have histological evidence of disease. Endomysial antibodies were detected in 11 of 12 patients and no false-positive cases were observed. Antigliadin antibodies were 75% sensitive and 88% specific. CONCLUSIONS: Our study demonstrated that screening using the endomysial antibody test is highly sensitive and specific for detecting celiac disease; however, almost 10% can be missed. The addition of lactulose/mannitol permeability testing to the screening protocol allowed us to detect all relatives who actually presented with evidence of gluten sensitivity. Sucrose permeability exhibited a lower sensitivity; however, it did detect other endoscopically visible lesions.
Adolescent↗
EsophaCoil: long-term results in 81 patients.
BACKGROUND: Cancer of the esophagus and gastric cardia cause progressive dysphagia. Half of patients are not amenable to surgical resection; of those who are, about 20% will suffer either from local recurrence or anastomotic strictures. Self-expandable metallic stents of diverse characteristics have been used in these clinical conditions. However, expandable metallic stents have several drawbacks: low radial force, migration, epithelial trauma, and tumor ingrowth. We herein report our long-term experience with EsophaCoil, a self-expandable esophageal metallic coil, in 81 patients. METHODS: From January 1993 to July 1996, 84 stents were placed in 81 consecutive patients (53 men and 28 women, mean age 69.8 years (range 40 to 90 years). 41 patients had esophageal squamous cell carcinoma, 32 adenocarcinoma of the esophagus and cardia, 5 mediastinal metastasis, 1 sarcoma, and 2 had benign esophageal strictures. Five patients had bronchoesophageal fistulas. Mean dysphagia score before treatment was 3.5, mean stricture length 6 cm. Most patients were hospitalized for at least 24 hours after stent implantation. Patients were followed and early and late complications were recorded. RESULTS: Stents were successfully placed in all patients. Dysphagia improved in 96% of patients (score dropped from 3.5 to 1.2). Mean patient survival after stent insertion was 4 months (range 0.5 to 20 months). Bronchoesophageal fistulas were closed in all 5 cases. Early complications occurred in 11 patients. These were severe in 3 (esophageal perforation) and mild in 8 patients (precordial pain lasting 24 to 48 hours). Late complications occurred in 18 patients and included migration to the stomach (5 patients), stent breakage (5 among the first 20 cases), food impaction (5), tumor overgrowth (2), and bleeding (1). CONCLUSIONS: In a long-term follow-up, EsophaCoil was effective in the palliative treatment of dysphagia caused by malignant esophageal strictures, including cases of fistulas, having low malfunction and migration rates. No tumor ingrowth was seen.
Adenocarcinoma↗
Usefulness of videoduodenoscopy and vital dye staining as indicators of mucosal atrophy of celiac disease: assessment of interobserver agreement.
BACKGROUND: The present study was designed to determine the diagnostic usefulness of videoduodenoscopic inspection alone and the addition of vital dye staining in the detection of celiac disease. We additionally sought to evaluate interobserver agreement for specific duodenoscopic markers of mucosal atrophy. METHODS: One hundred sixty-seven consecutive subjects who underwent duodenoscopy for intestinal biopsy were included in a prospective controlled study. Endoscopic examination was performed by experienced endoscopists according to a set protocol using methylene blue (1%) dye. All procedures were recorded on videotape, but only 20 (10 with atrophy and 10 normal) were used in a blinded, independent, randomized analysis by five reviewers to evaluate interobserver agreement. Endoscopic signs indicative of mucosal atrophy were as follows: reduction in the number or loss of Kerkring's folds, "scalloped" folds, "mosaic pattern," and visualization of the underlying blood vessels. RESULTS: Eighty-seven patients had celiac disease (57 newly diagnosed, 30 when treated). Seven treated patients had nonatrophic mucosa. In 80 patients the final diagnosis excluded celiac disease. Videoendoscopic inspection alone correctly identified 75 of 80 patients with complete mucosal atrophy and 86 of 87 with normal mucosa. False-negative diagnoses occurred in treated celiac patients with mild atrophy. Mosaic pattern (89%) and scalloped folds (86%) were the most useful endoscopic signs. Vital dye staining, as assessed by experienced endoscopists, provided identical results to those obtained by inspection alone. Sensitivity, specificity, and positive and negative predictive values for the presence of one or more than one feature were 94%, 100%, 100%, and 96%, respectively. The agreement (kappa statistics) among observers was excellent for the mosaic pattern (kappa: 0.76 for both the videoendoscopic inspection alone and dye staining) and the scalloped folds (kappa: 0.83 and 0.76, respectively) and was fair (kappa: 0.41 and 0.59, respectively) for the reduction in the number or loss of duodenal folds. CONCLUSION: This study confirms that videoduodenoscopy is useful in the detection of intestinal atrophy. Dye staining produces a better delineation of scalloped folds and mosaic pattern in the atrophic mucosa, but did not provide additional information to the expert endoscopist. Finally, interobserver agreement was excellent for the most prevalent signs.
Adult↗
Hb Setif [alpha 94(G1)Asp-->Tyr] in Malta.
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Aged↗
Deficits of spatial learning and working memory in spontaneously hypertensive rats.
It is possible that behavioral dysfunction, including cognitive, perceptual and psychomotor impairments in hypertensive subjects, can be the result of the high blood pressure. The aim of this study was to evaluate the performance of the spontaneously hypertensive rats (SHR) in the acquisition and execution of tasks in an 8-arm radial maze. Male Wistar normotensive rats (CON, n = 11) and SHR (n = 12), 3 months old, were first submitted to a series of training sessions to enter each of the 8 arms once in a given session (task acquisition), and errors (revisiting an arm in the same session) were computed. Errors before and after two delay intervals (5 s and 1 h, introduced between the fourth and fifth arm choice) were measured. These delayed tests allowed us to evaluate the working memory in different terms. It was observed that the SHR group made slightly more errors during the acquisition sessions and in the execution of the post-delay of 5-s interval tests, and significantly in the execution of the post-delay of 1-h interval tests compared to the CON. These results show that the SHR has a deficiency in the performance of the radial maze, suggestive of impairment of learning and working memory, mainly for a long-term memory, corroborating the hypothesis about the possible behavioral consequences of hypertension.
Animals↗
Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer.
From January 1990 to April 1993, 60 oesophageal cancer patients were enrolled in a protocol of non-surgical treatment that consisted of induction chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy consisted of cisplatin 40 mg/m2 intravenous bolus days 1, 2, 14, 15; 24 h continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2 days 1 and 14; leucovorin 20 mg/m2 days 1 and 14 given before and with 5-FU; bleomycin 30 UI days 1 and 14; mitomycin C 10 mg/m2 day 14. Concurrent chemoradiotherapy consisted of 60 Gy (6 weeks) from day 21 and cisplatin 70 mg/m2 days 28, 42 and 56; leucovorin 20 mg/m2 followed by 5-FU 425 mg/m2 days 28, 35, 42, 49 and 56. Complete response occurred in 44 of 55 evaluable patients (80%). The median survival is 32 months; the actuarial survival at 40 months is 35% (CI 18-53). These results appear improved over those reported with surgery or radiation alone, and suggest that organ preservation as a secondary treatment goal should be vigorously investigated.
Adult↗
Serological markers identify histologically latent coeliac disease among first-degree relatives.
BACKGROUND AND AIM: Serological markers detect asymptomatic coeliac disease among first-degree relatives of patients with sprue. However, some relatives with coeliac disease-related antibodies have 'normal' jejunal mucosa by conventional histology. Whether these serological abnormalities represent false-positives or are consequences of gluten sensitivity is not known. Our aim was to evaluate, through quantitative histology, intestinal biopsies of asymptomatic relatives of probands seeking abnormalities consistent with latent coeliac disease. MATERIALS: Fifty-nine intestinal biopsies obtained from asymptomatic relatives were evaluated; 40 samples were suitable for histological quantification. Seven samples showed severe mucosal atrophy (coeliac disease) and 33 were considered as 'normals'. In the 'normal' group, nine samples were obtained from patients with one or more positive serological tests and 24 from those with negative tests. Morphometry was compared for samples obtained from healthy control individuals (n = 10) and for those from coeliac patients (n = 7). METHODS: Serological tests used were: antigliadin antibodies type immunoglobulin (Ig)A and IgG (enzyme-linked immunosorbent assay), antirrecticulin antibody (immuno-fluorescence) and endomysial antibody (immunofluorescence). Biopsy samples were obtained with endoscopic forceps from the distal duodenum (second portion). Quantitative histology of duodenal biopsies was performed with a computerized image analysis system. RESULTS: Relatives with positive serology showed shorter villi (P < 0.05) and higher number (P < 0.01) and numerical density (P < 0.01) of intraepithelial lymphocytes in crypts than healthy controls. Numerical density of intraepithelial lymphocytes in crypts in antibody-positive patients was significantly higher than that observed in relatives with negative serology (P < 0.03). Four of nine (44%) relatives with positive serology had a number of intraepithelial lymphocytes in crypts within the range of coeliac disease patients. However, only one patient with negative serology (4%) was in this range. CONCLUSION: Our study shows quantitative histological evidence that relatives of probands with positive coeliac disease-related serology are not false-positives, and that they should be considered as individuals with latent coeliac sprue.
Adolescent↗
[Botulinum toxin is effective in the short-term treatment of esophageal achalasia. Preliminary results of a randomized trial].
UNLABELLED: Botulinum toxin (BoTox) is a potent inhibitor of the release of acetylcholine from terminal nerves and has been used successfully in spastic disorders of skeletal muscle. Its used for the treatment of disorders of gastrointestinal smooth muscle has recently been explored. In this study we evaluated the efficacy of transendoscopic injection of BoTox in 13 symptomatic patients with achalasia G II (Siewert classification) without previous treatment of an ongoing randomized-controlled trial. Patients were blindly randomized to administrate: a) 8OU of BoTox were injected in four quadrants (1 ml in each quadrant-20 U/ml) (n = 8), b) normal saline solution as placebo injected in the same way (n = 5). Patients who did not respond were retreated in an open design with the same schedule of BoTox. BoTox or placebo were injected directly into the lower esophageal sphincter (LES), located by manometric and endoscopic procedures, via sclerotherapy injector. Response to treatment was assessed by changes in symptoms score, weight, LES pressure, barium esophagograms and endoscopy. All determinations were repeated at basal and after 7-30-60 and 90 days of treatment. Post treatment response was considered positive if at one month, 3 of 4 parameters were improved. No evidence of response to BoTox were assessed in 3 patients. At 90 days, 10 patients remain well and data are as follows: (mean +/- SD) symptoms score: (Pre: 3.23 +/- 0.44) (Post: 1.31 +/- 0.95); LES pressure (mmHg) (Pre: 53, 15 +/- 66.31 +/- 7.49); % reduction of esophageal diameter 55% (p < 0.0001) (pair T-test). Relaxation of LES did not change after treatment. There were no side effects related to BoTox injection. CONCLUSIONS: Endoscopic intrasphincteric BoTox injection is safe, simple and effective in the short term treatment for achalasia. Further studies are necessary for evaluation of long term effects.
Adult↗
Teaching medical gerontology in Europe.
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Aged↗
[Esophageal involvement in progressive systemic sclerosis].
Systemic sclerosis is a collagen disease with high frequency of oesophageal affection, specially if we use manometry as an evaluation method that has a high rate of clinic complication in high rate of patients. The aim of the study was to evaluate the prevalence of the oesophageal affection through the clinical, radiological, endoscopical and manometrical studies and to compare the results with other authors. Between January 1978 and February 1993, we evaluated 101 patients with different clinical types of scleroderma 89 females and 12 males with ages between 16-83 (mean: 49, 19 years). In order to determine systemic sclerosis diagnosis following Masi Rodman criterion's we found from 101 cases 83 had dysphagia (82.2%) motor 66 (65%) organic 17 (34.7%) GER was seem in 41 cases (40.5%). According to Heitz's radiological classification: I: 26 patients (25%) II: 58 patients (52.4%) III: 19 patients (18.8%) IV: 17 patients (16.9%). In reference to Neschis manometric classification we found II 88 (76%) III 77 (76%) In accordance with endoscopical classification we found I: 16 (15.8%); II: 49 (48.5%); III: 19 (18.8%); IV: 17 (16.9%); Although this motor and organic oesophageal alterations have an evident diagnostic value, they have also been referred in another metabolic and collagen diseases but with lesser frequency than was found in the systemic sclerosis by us.
Adolescent↗