Gastrointestinal symptoms and Helicobacter pylori infection in school-age children residing in Porto Torres, Sardinia, Italy.

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.

Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib.

BACKGROUND: In a multicenter clinical trial in North America and Europe that tested the cathepsin K (catK) inhibitor balicatib for the treatment of osteoporosis, several patients developed hardening of the skin. OBJECTIVE: We sought to characterize these observed adverse events. METHODS: Patients with skin hardening were examined by a local dermatologist. All of those patients except one had at least one biopsy specimen taken from affected skin, which was read by local and two central dermatopathologists. Workup was directed for consideration of systemic scleroderma. RESULTS: Nine patients of 709 treated with balicatib developed skin hardening and were given a diagnosis of morphea-like skin changes. No such events were observed in patients taking placebo or the lowest balicatib dose. After discontinuation of balicatib, skin changes resolved completely in 8 and partially in one patient. LIMITATIONS: Each patient was seen by a different dermatologist in 6 different countries. CONCLUSIONS: These observations are likely dose-related adverse effects of balicatib. Although catK was originally thought to be expressed only in osteoclasts, it has more recently also been found in lung and dermal fibroblasts and been implicated in the degradation of the extracellular matrix in the lung and the skin. It is therefore plausible that the observed dermal fibrosis in balicatib-treated patients is a result of impaired degradation of extracellular matrix proteins and may represent a class effect of catK inhibitors. We recommend that further exploration of catK inhibition for the treatment of osteoporosis or cancer should include monitoring for similar adverse effects.

Health properties of the Italian San Martino® mineral-rich water: A self-controlled pilot study.

The effect of hyper-mineral waters on human health has long been debated. This pilot study evaluated the influence of San Martino® water (Sardinia, Italy), on clinical and biological parameters, following the treatment of 10 hospitalized patients. Crenotherapy consisted of 1-2 L of the water daily for 10 days. A complete blood count, serum electrolytes, liver and kidney function tests, fasting lipid profile and plasma glucose, and abdominal ultrasound imaging were assessed before and at the end of treatment. In addition, body weight, dyspeptic symptoms, bowel movements, diuresis, uricuria and blood pressure were evaluated daily. According to its physico-chemical properties, the water is hyper-mineral (TDS 2808 mg/L) with a high content of bicarbonate and iron. At the end of the study, diuresis increased by 60% (850 vs 1295 ml/24 h, P = 0.009) and uricuria by 41% (362 vs 490 mg/24 h, P = 0.022) respectively, whereas plasma uric acid level decreased by 7% (4.7 vs 4.3 mg/dL, P = 0.043). Compared to the basal values, serum gamma-glutamyl transferase, alkaline phosphatase and total bilirubin levels, showed a reduction of 65% (31 vs 18 U/L, P = 0.022), 15% (96 vs 90 U/L, P = 0.041), and 11% (0.53 vs 0.45 g/dL, P = 0.041), respectively. Bowel movements improved in 62.5% of patients with constipation, and 80% of dyspeptic patients experienced symptoms relief. Compliance to the treatment reached 100%. Mild differences were observed in body weight and blood pressure, although not in ultrasound imaging during crenotherapy. These findings suggest that the San Martino® hyper-mineral water may have some benefits to human health. Additional studies with a larger-sized cohort and for a longer period are needed to confirm these preliminary results.

Split-brain syndrome after hepatic transplantation: a tacrolimus-related vasculitis?

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.

Selection of diagnostic tests for clinical decision making and translation to a problem oriented medical record.

The leading function of the physician is the clinical reasoning, which involves appropriate investigation of the problems of the patient, formulation of a diagnostic suspect based on the patient's symptoms and signs, gathering of additional relevant information, to select necessary tests and administration of the most suitable therapy. The problems of the patient are expressed by symptoms or signs or abnormal test results, requested for a variety of reasons. The entire scientific, as well as diagnostic approach, is based on three steps: to stumble in a problem; to try a solution through a hypothesis; to disprove or to prove the hypothesis by a process of criticism. Clinicians use the information obtained from the history and physical examination to estimate initial (or pre-test) probability and then use the results from tests and other diagnostic procedures to modify this probability until the post-test probability is such that the suspected diagnosis is either confirmed or ruled out. When the pre-test probability of disease is high, tests characterized by high specificity will be preferred, in order to confirm the diagnostic suspect. When the pre-test probability of disease is low, a test with high sensitivity is advisable to exclude the hypothetical disease. The above mentioned process of decision making has been transferred to a problem oriented medical record that is currently employed in our Clinic.

OLGA gastritis staging in young adults and country-specific gastric cancer risk.

Geographical differences have been shown in the clinical outcomes of Helicobacter pylori-associated gastritis phenotypes and in gastric cancer risk. This study tested whether the Operative Link on Gastritis Assessment (OLGA) staging correlated with gastric cancer risk in populations from 3 continents. Mapped gastric biopsies were obtained from 316 dyspeptic adults aged less than 41 years from 8 geographic areas that differed in gastric cancer risk. Gastric atrophy was assessed according to internationally validated criteria. Gastritis stage was established according to the OLGA staging system. The most prevalent gastritis stages were 0 to II, which included all subjects entered from Chile, Germany, India, Italy, and Thailand. Gastritis Stages III and IV were limited to the Chinese and Korean populations. Indians had a high prevalence of H pylori infection without high-stage gastritis. In populations at different cancer risk, the gastritis OLGA stage mirrored the gastric cancer incidence. Gastritis staging identifies a subgroup of higher-risk patients.

Bone disease in primary hypercalciuria.

Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α are high in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH patients. Even if most of the factors involved in this process have been identified, many aspects of this intriguing clinical condition remain to be elucidated.

Tissue transglutaminase activity in human gastric mucosa according to Helicobacter pylori infection.

IMPACT STATEMENT: Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H. pylori infection compared to H. pylori negative chronic gastritis and normal antral mucosa. These findings suggest that t-TG has a role in the natural history of human gastritis, which requires further investigation but may be an avenue for new therapeutic options.

Clinical and genetic profile of patients with seronegative coeliac disease: the natural history and response to gluten-free diet.

OBJECTIVES: Patients with clinical, genetic and histological features of coeliac disease (CD), but negative for serological markers, pose a significant clinical problem. The aim of this study was to outline a specific profile, and to evaluate the natural history and response to gluten-free diet (GFD) of patients with seronegative CD. METHODS: patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA-DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available. RESULTS: 48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA-DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42% vs 22%; p<0.05). After a 1-year GFD trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative CD (25%) experienced the occurrence of autoimmune diseases during a median follow-up of 133 months (range 72-192). CONCLUSIONS: Patients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.

Bisphosphonates decrease telomerase activity and hTERT expression in MCF-7 breast cancer cells.

Bisphosphonates are important in the management of tumours with secondary bone involvement. Recent findings have suggested that these drugs also have an effect on primary tumour burden. Telomerase is a cellular ribonucleoprotein reverse transcriptase responsible for elongation of the telomere. Telomerase expression is increased in many cancers. We studied the direct effects of clodronate, alendronate, and pamidronate (from 10(-6) to 10(-4) M) on MCF-7 human breast cancer cell line. In particular, we investigated their effect on viability, proliferation, apoptosis, human telomerase reverse transcriptase expression (h-TERT) by RT-PCR and telomerase activity. Alendronate and pamidronate showed an inhibition of viability (-63 and -35%, respectively; p < 0.0001) and proliferation of cancer cells, while no effect was observed with clodronate. Amino-bisphosphonates induced a significant increase of apoptosis in MCF-7. In addition, they showed a significant decrease in telomerase expression and activity with respect to control and to clodronate.

[Fungal infections of the gastrointestinal tract]. / Micosi del tratto digestivo.

In immunocompetent subjects fungal infections of the gastrointestinal tract are uncommon. Candida esophagitis remains the single most common fungal infection in immunocompromised hosts or in H. pylori- infected patients who receive antibiotic therapy. Enteric fungal infections are uncommon even in HIV-infected patients. Antifungal agents such as amphotericin B, ketoconazole, fluconazole, and the various formulations of itraconazole are effective for most cases.

Risk Factors Associated with Helicobacter pylori Infection among Children in a Defined Geographic Area.

Factors influencing the pattern of Helicobacter pylori infection among children living in adjacent urban and rural areas of northern Sardinia, Italy, were compared. The seroprevalence of H. pylori infection was 22% (625 of 2810 children) in the study population and was significantly higher among children in rural areas (37%) than in urban areas (13%) (odds ratio [OR], 3.8; 95% confidence interval [CI], 3.2-4.7; P<.005). This difference was consistent within each age group. In rural areas, children who had dogs were at greatest risk for H. pylori infection (OR, 1.8; 95% CI, 1.3-2.6; P<.05). No association was seen between H. pylori seropositivity and a history of breast-feeding. Urban children attending day care centers had a higher prevalence of infection (17%) than did those who never attended (12%) (OR, 1.5; 95% CI, 1.1-2.0; P<.05). The epidemiology of H. pylori infection is complex; even within the same geographic area, different factors influence acquisition of H. pylori infection.

An inter- and intra-laboratory comparison of breath ¹³CO2analysis.

BACKGROUND: ¹³C breath test analysis requires accurate ¹³CO2measurements. AIM: To perform a multicentre study to evaluate the repeatability and reproducibility of breath ¹³CO2analysis. METHODS: Two series of 25 paired randomly coded tubes (each consisting of 23 ¹³CO2-enriched breath samples and two samples of standard reference pure CO2with certified δ ¹³C(PDB)) were sent to participating centres for ¹³CO2measurement. Each series of tubes was analysed 10 days apart. The repeatability and reproducibility of ¹³C measurements was assessed by Mandel's k and h statistics. RESULTS: Twenty-two centres participated in the study: 18 showed good inter- and intra-laboratory variability, whilst four showed abnormally high inter- or intra-laboratory variability. Breath test results were also significantly affected by the accuracy of the ¹³C analytical procedures. CONCLUSIONS: A low accuracy of ¹³C measurements may significantly affect the results of breath tests, leading to inappropriate clinical decisions. Standardization of ¹³C analysis is required to guarantee optimal ¹³C measurements and accurate ¹³C breath test results.

Active peptic ulcer disease in patients with hepatitis C virus-related cirrhosis: the role of Helicobacter pylori infection and portal hypertensive gastropathy.

BACKGROUND & AIM: The relationship between Helicobacter pylori infection and peptic ulcer disease in cirrhosis remains controversial. The purpose of the present study was to investigate the role of H pylori infection and portal hypertension gastropathy in the prevalence of active peptic ulcer among dyspeptic patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: Patients undergoing upper endoscopy with compensated HCV-related cirrhosis were enrolled. Child-Pugh's score was determined at the entry. Variceal size was measured endoscopically and the severity of portal hypertensive gastropathy was graded. H pylori infection status was determined by urea breath testing and/or histology. RESULTS: A total of 178 patients positive for HCV (A and B Child-Pugh's score) were prospectively included. The prevalence of H pylori infection was 43%. An active peptic ulcer was found in 14 patients (8%) and was significantly more common among those with H pylori infection (16% versus 2% in H pylori uninfected patients, odds ratio: 8.0). No association was observed between H pylori infection and variceal size, or hypertensive gastropathy. CONCLUSIONS: Patients with compensated cirrhosis and H pylori infection showed higher risk of developing a peptic ulcer. Clinical relevance of this result would be that dyspeptic patients with HCV-related cirrhosis may benefit from preventive screening and eradication of H pylori, especially those with features of insufficient hemostasis.

[Logical structure of the problem oriented clinical record. A combined Popper-Bayes approach]. / La struttura logica della cartella clinica orientata per problemi. Un approccio combinato Popperiano-Bayesiano.

The problem-oriented medical record is a tool whose correct compilation meets the requirements of the law as well as the need for continuing medical education within the logic of clinical decision making. The reading of the contents of a record allows people to evaluate the correspondence between the "thinking" and the "doing" of a doctor, as well the objectivity of the facts--that is, the truth related to the reasons for a patient's admission to hospital and the nature of his or her illness. To this aim, the authors suggest a structural logical iter in concordance with the lines of hypothetical-deductive epistemology, in contrast to inductive epistemology, as tradition has always suggested. The latter, in fact, proposes to start from singular observations and proceeding, by successive steps, towards a diagnosis. It thus neglects to take error into consideration, and therefore the differential diagnostic process, and ignores the fact that one cannot pass from single descriptions to universal (diagnostic) laws on the basis of logic. The process of falsification therefore plays a central role in the diagnostic procedure and thus in the construction of the medical record. This falsification process is centered, according to the most recent epistemology, on the logical schemes of Popper-Hempel and Bayes. The authors propose an integrated combination of both schemes to enable a correct approach to diagnostic hypothesis and to differential diagnosis, with their relevant legal, didactic and administrative repercussions.

Broken heart in elderly patients: two clinical observations.

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.

Diagnostic pathways of the complex patients: rapid intensive observation in an Acute Medical Unit.

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.

The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.