[Show abstract][Hide abstract] ABSTRACT: Background: Helicobacter pylori infection is typically acquired in childhood, and following the acute event, it is thought that most infections remain asymptomatic. H. pylori has been suggested to protect against diarrhea in childhood. Aim: To examine the role of H. pylori in gastrointestinal symptoms in children. Materials and Methods: A cross-sectional sero-epidemiologic study was conducted in Porto Torres, Sardinia, Italy. Demographic information, socioeconomic factors, and the frequency of upper gastrointestinal symptoms during the previous 3 months (e.g., abdominal pain, diarrhea, nausea, heartburn, halitosis, slow digestion, belching, and weight loss) were evaluated by a questionnaire. H. pylori status was determined by ELISA. Results: Approximately 95% (N = 1741) of school children between the age of 6 and 15 years from Porto Torres participated. The sero-prevalence of H. pylori infection was 13.3% (229/1727) and similar in boys (13%) and girls (14%) (p = .57). Nausea/vomiting (odds ratio (OR) = 2.2 (95% CI = 1.2-5.1)) and diarrhea (OR = 2.1 (95% CI = 1.3-2.8)) were each significantly associated with H. pylori infection, and these associations remained significant after controlling for other study variables. There was no significant association between H. pylori and abdominal pain or heartburn (p > .25). Conclusions: The study does not support either a role of H. pylori infection in abdominal pain in children or a protective role against diarrheal illnesses or nausea/vomiting.
[Show abstract][Hide abstract] ABSTRACT: Background Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autoso-mal dominant disorder, characterized by recurrent, potentially life-threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1-INH) isolated from human plasma. Objectives This open-label extension to a European, Israeli and Argentinean randomized study (NCT00262301) aimed to investigate the efficacy and safety of recombinant human C1 inhibitor (rhC1-INH) as a first-line treatment following an HAE attack, together with its effect on subsequent attacks. Methods An HAE-specific visual analogue scale (VAS) 0–100 mm was used by patients to assess the severity of attack at four anatomical locations. Patients were treated with one, single-vial, fixed-dose of rhC1-INH (2100 U), followed by up to two further vials at the investigators discretion. The primary end-point was the time from first rhC1-INH injection to first onset of relief of symptoms (20 mm decrease on VAS). Response to treatment was defined as the onset of relief within 4 h. Results A total of 57 patients were treated for 194 HAE attacks. Overall, sustained relief of symptoms was achieved in 87% of rhC1-INH-treated patients within 4 h of treatment, with 57% of attacks requiring only one vial of rhC1-INH. When categorized by successive attacks experienced by individual patients, the response rate to rhC1-INH treatment was 96%, 83%, 87%, 80% and 80% for attacks 1–5 respectively. Treatment with rhC1-INH was well tolerated, with no discontinuations owing to treatment-emergent adverse events and no adverse events relating to immunogenicity. Conclusions and Clinical Relevance Treatment with rhC1-INH provides fast-onset relief for an HAE attack, with a high rate of therapeutic response maintained throughout subsequent attacks.
Clinical and Exprimental Allergy. 06/2012; 42:2012--929.
[Show abstract][Hide abstract] ABSTRACT: Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autosomal dominant disorder, characterized by recurrent, potentially life-threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1-INH) isolated from human plasma.
This open-label extension to a European, Israeli and Argentinean randomized study (NCT00262301) aimed to investigate the efficacy and safety of recombinant human C1 inhibitor (rhC1-INH) as a first-line treatment following an HAE attack, together with its effect on subsequent attacks.
An HAE-specific visual analogue scale (VAS) 0-100 mm was used by patients to assess the severity of attack at four anatomical locations. Patients were treated with one, single-vial, fixed-dose of rhC1-INH (2100 U), followed by up to two further vials at the investigators discretion. The primary end-point was the time from first rhC1-INH injection to first onset of relief of symptoms (≥ 20 mm decrease on VAS). Response to treatment was defined as the onset of relief within 4 h.
A total of 57 patients were treated for 194 HAE attacks. Overall, sustained relief of symptoms was achieved in 87% of rhC1-INH-treated patients within 4 h of treatment, with 57% of attacks requiring only one vial of rhC1-INH. When categorized by successive attacks experienced by individual patients, the response rate to rhC1-INH treatment was 96%, 83%, 87%, 80% and 80% for attacks 1-5 respectively. Treatment with rhC1-INH was well tolerated, with no discontinuations owing to treatment-emergent adverse events and no adverse events relating to immunogenicity.
Treatment with rhC1-INH provides fast-onset relief for an HAE attack, with a high rate of therapeutic response maintained throughout subsequent attacks.
[Show abstract][Hide abstract] ABSTRACT: Tako-tsubo cardiomyopathy (idiopathic or transient left ventricular apical ballooning syndrome [ABS]) is a reversible condition frequently precipitated by a stressful trigger that clinically mimics an acute ST-elevation myocardial infarction. Characteristically, hypokinesis or akinesis occurs in the mid- and apical segments of the left ventricle in the absence of epicardial coronary lesions. Preserved or hyperdynamic function of the basal myocardial segments results in apical ballooning, assuming the shape of a Japanese pot used to catch octopus (a takotsubo). We report on 2 well over 70 years old women (78 and 82 years) admitted to the emergency room with chest pain. Clinical signs, ECG alterations and high troponin I in both patients imposed urgent diagnostic testing and management. The electrocardiographic findings were consistent with acute myocardial infarction and transthoracic echocardiography showed in both simultaneous apical akinesia and a hyperkinetic basal area with a moderately reduced left ventricular ejection fraction. Coronary angiography, performed on an emergency basis, in both cases revealed minimal luminal irregularities, with no evidence of plaque rupture or thrombus. The wall motion abnormality extended beyond the distribution of any single coronary artery, making it less likely that an occlusive thrombus had spontaneously dissolved or that intermittent vasospasm had occurred. Taken together, these findings were consistent with ABS, and critical observations on coronary angiography indicated the diagnosis by exclusion. The patients were seen in the clinic 4 weeks after discharge. They had had no recurrent chest pain, and had returned to the normal life they had had before the cardiovascular event. A repeat echocardiography showed a normalized estimated ejection fraction in both patients. ABS is a diagnosis of exclusion and its incidence is probably underestimated in elderly patients in whom coronary angiography is not common.
Aging clinical and experimental research 02/2012; 24(1):97-103. · 1.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present-day patients have complex diseases that are responsible for the great increase of medical interventions, overcrowding in emergency departments and access to the wards, increased waiting times and length of stay, difficult discharge, increased readmission rate and finally increased mortality. By breaking the steps of the patients pathways it allows us to simplify the problems and to face the individual aspects of the complexity related to the management of patients in the hospital. One solution that has been growing in popularity is the rapid intensive observation of the patients in acute hospital setting within Internal Medicine wards. This model has been otherwise defined with different terminology, but the most widely used name is Acute Medical Unit (AMU). We describe the model of an AMU within an Internal Medicine department as proposed and adopted in Anglo-Saxon countries, the methods of clinical approach and the practical organisation of the units in close collaboration with the ED ward. Finally we report our experience at an Internal Medicine department in Padova and the initial results obtained during the first 4 months of the project. Our approach of intensive rapid observation of intermediate risk patients admitted from the ED led to a significant reduction in the duration of hospitalization, without increasing readmission rate after discharge and fatality rate. Factors significantly associated to a short hospital stay were a preserved function and a lower number of previous admissions to the hospital. Several gray zones in the realisation and management of the project were identified and the possible solutions are still matter of discussion and debate.
Internal and Emergency Medicine 10/2011; 6 Suppl 1:85-92. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Differential diagnosis of dyspnea is vital for the management of respiratory failure, where routine parameters can now be integrated with thoracic ultrasound data. The objective of this study was to evaluate the validity and accuracy of this approach in a department of internal medicine.
We enrolled 152 patients consecutively hospitalized with a diagnosis of dyspnea. After clinical evaluation, chest radiography, biochemical assays (NT-proBNP), and emergency treatment, patients underwent ultrasound examination of the lungs. Results were considered positive if the total number of lines B was higher than 8. The ultrasound examination and NT-proBNP assay were repeated after 48 h. The gold standard was the clinical diagnosis of heart failure made by medical experts in accordance with AHA guidelines.
The group of patients with positive ultrasound findings had a higher frequency of heart failure diagnoses (X(2) 92.5, p < 0.005) and significantly higher values of NT-proBNP (10,384 ng/l vs 3889 ng/l, p < 0.05). Moreover, the decrease in the number of B lines at 48 h was significantly greater (p < 0.005) among patients treated for heart failure. There were no significant changes in the values of NT-proBNP (p = 0.37).
In conclusion we have shown that even in a department of internal medicine, lung ultrasonography is a useful tool for diagnosing respiratory insufficiency and monitoring its response to therapy.
[Show abstract][Hide abstract] ABSTRACT: US (US) examination of the abdomen has acquired a growing role in the investigation of abdominal pain; however its role in the diagnosis of some important causes of abdominal pain is still under investigation. The aim of this study was to evaluate the role of US of the abdomen in the diagnosis of abdominal pain in patients referred to a department of internal medicine.
A retrospective analysis was carried out on 248 US examinations performed in our department due to abdominal pain. For each examination the data written on the request form were registered as well as US findings which could be correlated with abdominal pain.
In 105 patients (42%), US examination of the abdomen resulted in a relevant clinical finding and was thus considered positive. A high percentage of patients were elderly (>65 years; 52%) and very elderly (>80 years; 24%); these patients showed a significantly higher percentage of positive US scans. The proportion of positive scans was not significantly different between localized and non-localized pain. Specific pain location was associated with US findings such as hepatic masses, ovarian masses and renal stones, whereas non-localized pain was associated with abdominal free fluid and fluid-distended bowel loops.
A high percentage of US examinations identified conditions that could possibly cause abdominal pain. Diagnostic yield of abdominal US was higher in elderly and very elderly patients. When a US examination is requested, it should always be evaluated within the clinical context. The physician should be aware of the great value of abdominal US in the diagnosis of the various causes of abdominal pain, but also of its possible limitations.
[Show abstract][Hide abstract] ABSTRACT: An unusual case of inter-haemispheric disconnection syndrome occurring in a patient who had undergone hepatic transplantation is presented. The underlying disorder, at first wrongly interpreted as encephalitis, was found to be severe, diffuse cerebral vasculitis. The hypothesis that treatment with tacrolimus might have caused, or at least favoured the vascular damage is discussed.
[Show abstract][Hide abstract] ABSTRACT: The clinical evaluation of patients with chronic diarrhea and/or abdominal pain requires a complex work-up. The aim of the study was to evaluate whether routine duodenal biopsy sampling of macroscopically normal mucosa of patients with irritable bowel syndrome-like symptoms undergoing upper endoscopy assists in diagnosis and management.
Consecutive adults scheduled for upper endoscopy for evaluation of uninvestigated dyspepsia and abdominal pain and/or chronic diarrhea based upon the history, were enrolled. Gastric biopsies and 3 duodenal biopsies were taken for histological evaluation.
A total of 786 sets of biopsies from 262 consecutive patients (200 females and 62 males, mean age 46 years; range: 15-82), were analyzed. Microscopic damage was observed in 212 of 262 patients (81%) with normal mucosa. Mild to moderate and severe duodenitis or villi atrophy was histologically confirmed in 65%, 26% and 8% of 212 patients respectively. The negative predictive value of a normal appearing duodenal mucosa was 19%. Additional tests confirmed celiac disease in 12 patients. Lactose malabsorption was present in 42%, bacterial overgrowth in 14%, and H. pylori infection in 28%. Colonoscopy performed in 92 patients revealed non specific colitis (25%), microscopic colitis (28%), Crohn's disease (1%), and diverticulosis (15%).
Duodenal biopsies revealed abnormalities in the majority of adults with chronic diarrhea and/or abdominal pain despite macroscopically normal gross findings. These results suggest that duodenal biopsies could be helpful in patients with chronic diarrhea and/or abdominal pain for the following work up.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the effects of risedronate (Ris) in the modulation of bone formation in rats with glucocorticoid (GC)-induced osteoporosis by histomorphometric, immunohistochemical and gene expression analyses.
We analyzed structure, turnover and microarchitecture, cyclooxygenase 2 (COX-2) levels and osteocyte apoptosis in 40 female rats divided as follows: 1) vehicle of methylprednisolone (vGC) + vehicle of risedronate (vRis); 2) Ris 5 μg/Kg + vGC; 3) methylprednisolone (GC) 7 mg/Kg + vRis; 4) GC 7 mg/Kg +Ris 5 μg/Kg. In addition, we evaluated cell proliferation and expression of COX-2 and bone alkaline phosphatase (b-ALP) genes in bone marrow cells and MLO-y4 osteocytes treated with Ris alone or in co-treatment with the selective COX-2 inhibitor NS-398 or with dexametasone.
Ris reduced apoptosis induced by GC of osteocytes (41% vs 86%, P < 0.0001) and increased COX-2 expression with respect to controls (Immuno-Hystochemical Score (IHS): 8.75 vs 1.00, P < 0.0001). These positive effects of Ris in bone formation were confirmed by in vitro data as the viability and expression of b-ALP gene in bone marrow cells resulted increased in a dose dependent manner.
These findings suggest a positive effect of Ris in bone formation and support the hypothesis that the up-regulation of COX-2 could be an additional mechanism of anabolic effect of Ris.
Arthritis research & therapy 01/2010; 12(4):R163. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zoledronic acid (Zol) is used successfully to inhibit bone resorption in tumor bone disease of various human cancer. Zol inhibits the mevalonate pathway and other potential targets include the inhibition of tyrosine phosphatase activity, disruption of metalloproteinase, secretion and down-regulation of the catalytic subunit of telomerase (hTERT). The six-transmembrane epithelial antigen of prostate protein (STEAP) is a new marker highly expressed at all phases of prostate cancer.
Here, we analyzed for the first time the effect of Zol on STEAP gene expression in prostate cancer cells.
We evaluated the effects of Zol in STEAP gene expression by RT real time PCR in androgen-sensitive (LNCaP) and androgen-non-sensitive (PC3 and DU145) cell lines. To confirm the pro-apoptotic effect of Zol, we also analyzed the caspase-3 gene expression, that resulted up-regulated in cancer cell apoptosis.
Zol strongly decreased cell viability and lowered STEAP gene expression in a dose-dependent manner. In addition, this effect was accompanied by an increase of apoptotic index and an up-regulation of caspase-3 gene expression.
Zol may affect cancer cells also by targeting the gene expression of STEAP.
Journal of endocrinological investigation 11/2009; 33(4):244-9. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone morbidity remains a major problem even after successful renal transplantation. We investigated the role of calcium-sensing receptor (CaSR) polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx) in 125 renal allograft recipients transplanted 44 +/- 23 months before. All patients underwent evaluation of the main biochemical parameters of calcium metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the lateral spine were obtained in 102 subjects to perform vertebral morphometry. High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were found in 54% and 97% of patients, respectively, with 40% of these showing vitamin D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but not CaSR polymorphisms, were found to be significant predictors of high PTH, whereas age and time since transplant were positively related with lower 25-hydroxyvitamin D values. PTH and time since transplant were significantly associated with VFx. Patients with two or more VFx showed serum PTH levels 50% higher than patients without fractures. We therefore conclude that persistent SHPT is a very common feature after renal transplantation and that, unlike CaSR polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2009; 25(4):841-8. · 6.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several non-invasive markers have been proposed to assess liver damage in NAFLD. We measured by ultrasound (US) the perihepatic adipose tissue thickness (PATT), i.e. the thickness of the fat between the abdominal muscular layer and the hepatic surface, in addition to waist circumference, BMI, biochemistry and serum adipokines, to predict the severity of liver damage in NAFLD.
63 NAFLD patients and 45 controls were studied. PATT and US steatosis score were assessed in all patients. Histology was obtained in those with an US steatosis score greater or equal to 2.
PATT was 13.5 + or - 4.1 mm in NAFLD vs 8.0 + or - 4.1 in controls (p less than 0.001). A PATT value of 11.2 mm seems to represent a cut-off below which NAFLD is unlikely. Test sensitivity, specificity and the area under the ROC curve were 100%, 50% and 75%, respectively, suggesting a good discrimination between patients with non-NASH and those with NASH or borderline NASH. In addition, PATT strongly correlated with waist circumference (p less than 0.001). Both PATT and waist circumference correlated with US steatosis, HOMA-IR, TNF-alpha, IL-6 and leptin. Based on a multiple logistic regression analysis, waist circumferences greater or equal to 110, 113 and 122 cm were associated with a probability over or equal to 50% of abnormal HOMA-IR, TNF-alpha and leptin values, respectively.
PATT and waist circumference could represent non-invasive markers predicting the severity of liver damage in NAFLD.
Journal of gastrointestinal and liver diseases: JGLD 03/2009; 18(1):61-6. · 1.85 Impact Factor