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.

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.

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.

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.

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.

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.

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.

Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: role of calcium-sensing receptor polymorphisms and vitamin D deficiency.

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.

Perihepatic adipose tissue thickness: a new non-invasive marker of NAFLD?

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: PATT and waist circumference could represent non-invasive markers predicting the severity of liver damage in NAFLD.

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.

Diet, lifestyle and gender in gastro-esophageal reflux disease.

BACKGROUND: Studies indicate that gastro-esophageal reflux disease (GERD) is associated with obesity, smoking, esophagitis, diet, and lifestyle. AIM: To identify risk factors associated with GERD among patients presenting to a tertiary GI clinic in Italy. METHODS: Patients with a first diagnosis of GERD based on heartburn and/or regurgitation and/or esophagitis at the endoscopic examination were enrolled. A control group with neither GERD symptoms nor esophagitis was enrolled from the same hospital. Each subject completed a questionnaire including demographic information, lifestyle (e.g., exercise, alcohol, coffee, chocolate, and soda consumption, smoking, having large meals), and frequency of bowel movement. For each participant the body mass index (BMI) was calculated. RESULTS: Five hundred subjects were enrolled including 300 GERD patients and 200 controls. Females had significantly higher prevalence of GERD than males (66 vs. 48%, P = 0.001, OR = 2.1, 95% CI = 1.5-3.1). There was an inverse relationship between the level of education and presence of GERD (76% of GERD patients has completed only elementary school (OR = 2.1, 95% CI = 1.7-4.9). Obesity (BMI of > or =95th percentile for their age/gender specific) was significantly related to GERD (OR = 1.8, P = 0.01). None of the other variables studied showed significant associations with GERD. Logistic regression analysis showed that BMI > or =95th percentile, gender, and low education level were significant risk factors for GERD. CONCLUSIONS: Understanding the epidemiology and risk factors for GERD in a region is the first step in designing prevention and treatment strategies.

Cryoglobulinemia related to hepatitis C virus infection.

A causal link among hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia, cryoglobulinemic glomerulonephritis, and vasculitis is strongly supported. HCV triggers autoimmune response in predisposed individuals that manifests as organ-specific and non-organ-specific autoantibodies and as polyclonal/monoclonal rheumatoid factor, which has a central role in causing damaging cryoglobulin and immune complex tissue levels. Immunologic events are mainly induced by HCV infection persistence, with excessive immune stimulation. Humoral immune dysfunction leads to autoantibodies and rheumatoid factor production with cryoglobulinemia, glomerulonephritis, vasculitis, neuropathy, and probably thyroiditis, and arthritis in rare cases. Cellular immune dysfunction leads to lymphocytic infiltration, proliferation, and cytokine production. Pegylated (or not) interferon-alpha in combination with ribavirin appears to be the treatment of choice for patients with symptomatic essential mixed cryoglobulinemia with or without glomerulonephritis. Novel treatment with rituximab is promising.