Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease.

OBJECTIVE: Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening. METHODS: We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam. RESULTS: PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed. CONCLUSION: In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.

In irritable bowel syndrome, postprandial abdominal distention is associated with a reduction of intestinal tone.

BACKGROUND: The pathophysiology of abdominal distention in irritable bowel syndrome (IBS) is still a matter of debate, but the relationship between modifications of intestinal tone and abdominal volume has never been analyzed. METHODS: Eighty-four patients affected by IBS and reporting moderate to severe abdominal distention were enrolled. Thirty-nine presented abdominal distention immediately after and forty-five presented abdominal distention independently of meal intake. Twenty healthy volunteers (HV), comparable for gender and age, were also enrolled. All the subjects underwent fasting and postprandial recto-sigmoid volume monitoring with barostat and abdominal girth measurement to evaluate abdominal distention. KEY RESULTS: In comparison with HV (75±13 mL) and with patients with meal-unrelated abdominal distention (135±56 mL), in the subgroup of patients with severe meal-related abdominal distention recto-sigmoid tone response to the meal was significantly reduced (mean increase of balloon volume 184±89 mL; P<.001), paralleling abdominal girth increase and occurring immediately after test meal intake. Meal-induced abdominal girth modification was significantly correlated with meal-related modification of recto-sigmoid tone (r=.71) and abdominal symptoms. CONCLUSIONS: In patients with IBS suffering from severe postprandial abdominal distention, a postprandial reduction of intestinal tone is associated with this bothersome symptom. Further studies are needed to evaluate whether drugs acting on the modification of intestinal tone could be useful in the treatment of these patients.

Rational design of dendritic thermoresponsive nanogels that undergo phase transition under endolysosomal conditions.

In the last few decades, the synthesis of nanodevices has become a very active research field with many applications in biochemistry, biotechnology, and biomedicine. However, there is still a great need for smart nanomaterials that can sense and respond to environmental changes. Temperature- and pH-responsive nanogels (NGs), which are prepared in a one-pot synthesis from N-isopropylacrylamide (NiPAm) and a Newkome-type dendron (ABC) bearing carboxylic acid groups, are being investigated as multi-responsive drug carriers. As a result, NGs have been developed that are able to undergo a reversible volume phase transition triggered by acidic conditions, like the ones found in endolysosomal compartments of cancer cells. The NGs have been thoroughly characterized using dynamic light scattering and spectroscopies, such as infrared, nuclear magnetic resonance, UV-visible, and stimulated Raman. Strong hydrogen bonds have been detected when the ABC moieties are deprotonated, which has led to changes in the transition temperatures of the NGs and a reversible, pH-dependent aggregation. This pH-dependent phase change was exploited for the effective encapsulation and sustained release of the anticancer drug cisplatin and resulted in a faster release of the drug at endolysosomal pH values. The cisplatin-loaded NGs have exhibited high toxicities against A549 cells in vitro, while the unloaded NGs have been found to be not cytotoxic and hemocompatible.

Hydrogen breath test in patients with severe constipation: the interference of the mixing of intestinal content.

BACKGROUND: The diagnostic accuracy of the hydrogen (H2 ) breath test might be reduced by the release of preformed H2 , trapped in hard stools. Test solution ingestion might induce the mixing of colonic content and a false positive result. We studied severely constipated patients, at diagnosis and after the normalization of bowel function, to clarify whether this mechanism affects test results. METHODS: Twenty functional constipated patients, 10 consecutive patients with functional diarrhea and 10 healthy volunteers underwent (i) a H2 breath test after lactulose, to exclude differences among the groups in fermenting capacity; (ii) breath H2 excretion monitoring after non-absorbable, non-fermentable PEG-electrolyte solution, to exclude the role of the delivery to the colon of preexisting fermentable substrates or of the release of preformed H2 entrapped in the feces; (iii) H2 measurement during a 7-h fasting period, to exclude the role of spontaneous variations of breath gas excretion; and (iv) breath H2 excretion monitoring after PEG, after normalization of bowel function. KEY RESULTS: All the subjects excreted similar amounts of H2 after lactulose. After PEG, only severely constipated patients showed significant breath H2 excretion, theoretically able to induce a false positivity of the lactose breath test in 70% of patients and a false positivity of glucose breath tests in 50% of patients. Breath H2 excretion after PEG disappeared if fecal consistency improved after therapy. CONCLUSIONS & INFERENCES: Severely constipated patients may harbor preformed gas in hard stools which can be released when mixing of the intestinal content is induced. This mechanism may interfere with breath test results.

Usefulness of abdominal ultrasonography with studies of the intestinal loops in Turner syndrome patients.

Turner syndrome, a chromosomal disorder caused by partial or complete absence of one of the two X chromosomes, is characterized by an increased incidence (compared with that in the normal population) of either autoimmune disorders, including chronic inflammatory bowel diseases, or angiodysplasia of the small intestine. Because ultrasonography and color Doppler ultrasound are widely used to investigate gastrointestinal disorders, we decided to carry out an ultrasound-based screening study in patients with Turner syndrome to determine whether this method might be useful in the follow-up of this population.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Visceral hypersensitivity and intolerance symptoms in lactose malabsorption.

Lactose malabsorption is not always associated with intolerance symptoms. The factors responsible for symptom onset are not yet completely known. As differences in visceral sensitivity may play a role in the pathogenesis of functional symptoms, we evaluated whether an alteration of visceral sensitivity is present in subjects with lactose intolerance. Thirty subjects, recruited regardless of whether they were aware of their capacity to absorb lactose, underwent an evaluation of intestinal hydrogen production capacity by lactulose breath test, followed by an evaluation of lactose absorption by hydrogen breath test after lactose administration and subsequently an evaluation of recto-sigmoid sensitivity threshold during fasting and after lactulose administration, to ascertain whether fermentation modifies intestinal sensitivity. The role of differences in gastrointestinal transit was excluded by gastric emptying and mouth-to-caecum transit time by (13)C-octanoic and lactulose breath tests. Lactulose administration induced a significant reduction of discomfort threshold in subjects with lactose intolerance but not in malabsorbers without intolerance symptoms or in subjects with normal lactose absorption. Perception threshold showed no changes after lactulose administration. Severity of symptoms in intolerant subjects was significantly correlated with the reduction of discomfort thresholds. Visceral hypersensitivity should be considered in the induction of intolerance symptoms in subjects with lactose malabsorption.

Meal induced rectosigmoid tone modification: a low caloric meal accurately separates functional and organic gastrointestinal disease patients.

BACKGROUND AND AIMS: Diagnosis of irritable bowel syndrome (IBS) is based on arbitrary criteria due to the lack of an accurate diagnostic test. The aim of this study was to evaluate whether rectosigmoid tone modification after a meal represents an accurate diagnostic approach. METHODS: In a secondary care setting, 32 constipation predominant and 24 diarrhoea predominant IBS patients, 10 functional diarrhoea and 10 functional constipation patients, 29 organic gastrointestinal disease patients, and 10 healthy volunteers underwent a rectal barostat test to measure fasting and postprandial rectosigmoid tone. Rectosigmoid response was assessed following three meals containing different amounts of calories: 200 kcal, 400 kcal and 1000 kcal. RESULTS: After 200 kcal, healthy volunteers and patients with organic diseases showed a reduction in rectosigmoid volume of at least 28% of fasting volume, indicating a meal induced increase in muscle tone. In contrast, patients with diarrhoea predominant IBS showed dilation of the rectosigmoid colon, indicative of reduced tone, and patients with constipation predominant IBS showed a mild volume reduction or no modification. Functional diarrhoea and constipation patients showed rectosigmoid tone modification resembling that of the corresponding IBS subtype. A 400 kcal meal normalised rectosigmoid tone in more than half of the constipation predominant IBS patients but none of the diarrhoea predominant IBS patients. In contrast, a 1000 kcal meal normalised tone response in all IBS patients. Sensitivity of the test was 100%, specificity 93%, positive predictive value 96%, and negative predictive value 100%. CONCLUSION: A postprandial reduction in rectosigmoid tone of at least 28% of fasting value after a low caloric meal accurately separates organic and functional gastrointestinal disease patients. This parameter may therefore be used in the positive diagnosis of IBS.

Treatment of small intestine bacterial overgrowth.

Removal of the predisposing condition, appropriate nutritional support to reintegrate both caloric and vitamin requirements and suppression of the contaminating bacterial flora represent the main of goals of the treatment of small intestine bacterial overgrowth. Generally, the polymicrobic nature of contaminating flora requires the administration of wide-spectrum antibiotics, but as yet we don't know which is the best pharmacological approach, in terms of drug, dosage and duration of therapy. There is no conclusive information regarding the most effective therapy that should be used. This paper reviews the efficacy of the different therapeutic approaches used.

Absorbable vs. non-absorbable antibiotics in the treatment of small intestine bacterial overgrowth in patients with blind-loop syndrome.

BACKGROUND: Small intestine bacterial overgrowth is associated with the presence of predisposing conditions, acting through different mechanisms. Therefore, the failure to define a standardized therapy may be due to a methodological bias: to treat a condition characterized by different pathophysiological mechanisms with the same pharmacological approach. Non-absorbable antibiotics could have a lower efficacy than absorbable drugs in patients with blind loops which exclude a portion of the intestine from the transit. AIM: To evaluate the efficacy of absorbable vs. non-absorbable antibiotics in this subgroup of patients. METHODS: A group of small intestine bacterial overgrowth patients with total gastrectomy or gastrojejunostomy and blind loop underwent a therapeutic trial comparing rifaximin to metronidazole. Seven patients underwent a course of rifaximin followed by a course of metronidazole on recurrence of symptoms. To compare the effect of the drugs, another two groups of patients underwent two consecutive courses of rifaximin or metronidazole. Hydrogen breath test after glucose administration and symptom severity measurement were performed. RESULTS: Both drugs reduced breath H(2) excretion but a much better improvement was achieved after metronidazole. Symptom improvement was higher after metronidazole. CONCLUSION: Metronidazole is more effective than rifaximin for the treatment of small intestine bacterial overgrowth associated with the presence of a blind loop.

The role of gastric accommodation in the pathophysiology of functional dyspepsia.

BACKGROUND AND OBJECTIVES: The pathophysiology of functional dyspepsia is not yet completely known. Several mechanisms have been suggested as having a role in symptom onset and impaired gastric accommodation to meal is one of the most frequent. This review will focus on the pathophysiological and clinical aspects of this abnormality. EVIDENCE AND INFORMATION SOURCES: Medical peer-reviewed literature was considered to elucidate the role of gastric accommodation in the pathophysiology of functional dyspepsia. STATE OF THE ART: Impaired gastric accommodation to meal is present in around 40% of patients with functional dyspepsia and it was shown to be associated with the presence of early satiety. Unfortunately, a definitive treatment of this abnormality with fundus-relaxing drugs is not yet available. PERSPECTIVES: Further studies are needed to better clarify the role of each single pathophysiological mechanism on clinical manifestations of functional dyspepsia. Research is still ongoing to offer a valid therapeutic approach.

Probiotics and functional abdominal bloating.

Functional abdominal bloating is a condition dominated by a feeling of abdominal fullness or bloating and without sufficient criteria for another functional gastrointestinal disorder. The currently used therapeutic approaches aim to reduce the volume of intestinal gas, thus increasing intestinal gas elimination or reducing its production. Some promising results have been obtained by the use of prokinetics, such as tegaserod and Prostigmine, and by the use of nonabsorbable antibiotics, such as rifaximin. Another therapeutic approach is represented by the administration of probiotics to modify the composition of colonic flora and thus the production of intestinal gas. The authors recently studied the effect of LGG, which proved to be more effective than placebo in reducing the severity of symptoms.

Endometrial carcinoma. Clinical and pathological correlations with survival and surgical treatment.

From 1978 to 1985 a total of 151 patients were treated for endometrial carcinoma. Of these, 25 patients underwent extrafascial abdominal hysterectomy and pelvic lymphadenectomy, 25 were treated according to Wertheim procedure and pelvic lymphadenectomy and 32 underwent intrafascial abdominal hysterectomy; 62 women underwent vaginal surgery, 7 of whom according to Shauta. A correlation between the degree of myometrial invasion, histological grading, hystological type and stage of the tumor showed no statistically significant difference. The 5-year actuarial survival rate was found to be 76.5%. A comparison between survival and age of patients showed a significant difference in the survival (p less than .01) of the group less than 55 years as compared to the older age group. As far as the surgical treatment instituted is concerned, no statistical difference in survival was found between patients operated vaginally and those operated abdominally (p greater than .05). The site of recurrences were then analyzed in 22 patients, 50% were local recurrences, and the remaining distant metastases. Of these only one patient was cured and is still free of disease 5 years after recurrence. The criteria used to select patients for vaginal surgery are also indicated.