Genetic test for lactase non-persistence and hydrogen breath test: is genotype better than phenotype to diagnose lactose malabsorption?

BACKGROUND: Adult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. The lactose breath test is a simple tool for diagnosis but the need for prolonged monitoring of hydrogen excretion has led to a genetic test proposal. The aim of this study was to compare the genetic test with the lactose breath test in order to give some insights into the clinical value of genetic testing. METHODS: Thirty-two consecutive functional patients underwent lactose breath test and lactase genetic polymorphism analysis (C/T 13910 and G/A 22018). Intolerance symptoms after lactose load were also monitored. RESULTS: All patients with positive lactose breath test showed homozygosis for both polymorphisms. Among the nine patients with a negative breath test result, six showed heterozygosis while three showed homozygosis. Intolerance symptoms were present in 16 homozygotic patients but also in one heterozygotic patient. The k value for the agreement between the genetic test and the lactose breath test was 0.74. CONCLUSION: A positive genetic test for lactase non-persistence indicates whether lactase activity decline may represent a clinical problem for the patient, but does not give information on actual patient symptoms. On the contrary, this information is already available by combining the lactose breath test with intolerance symptom evaluation. Lactose absorption phenotype may be not yet evident until young adult age.

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.

Reduced number and function of peripheral dendritic cells in coeliac disease.

Dendritic cells (DC) play a pivotal role in shaping the immune response in both physiological and pathological conditions. In peripheral blood at least two subsets, the myeloid and plasmacytoid, have been described as having different T stimulatory functions and a variable degree of maturation. Certainly, antigen presentation plays a crucial role in the pathogenesis of coeliac disease and circulating immune cells are thought to reflect the state of immune response within the gut. Therefore, we aimed to investigate the quantitative and phenotypical modifications of peripheral blood DC, together with their functional properties, in this pathological condition. Blood samples from 11 untreated patients before and after a course of gluten-free diet, 27 treated patients and 14 controls underwent flow-cytometric analysis, while immunomagnetically sorted DC from the CD patients and eight human leucocyte antigen (HLA)-DQ2/8(+) bone marrow donors were used to evaluate maturation status through the CD83 expression, cytokine profile for interleukin (IL)-6, IL-10, IL-12 and interferon (IFN)-alpha by enzyme-linked immunosorbent assay (ELISA), and functional properties by mixed leucocyte reaction before and after pulsing with digested gliadin. We found that in both untreated and treated patients, a significant reduction of the entire DC population, mainly the plasmacytoid subset, in comparison to healthy controls was observed. In active disease, an impaired allogenic lymphocyte reaction and a significant reduction of IFN-alpha production, paralleled by the presence of a more immature status, were also demonstrated. All the latter modifications have been reverted by pulsing DC with digested gliadin.

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.

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.

AEC set-up optimisation with computed radiography imaging.

Phototimer set-up is a critical procedure for dose and image quality optimisation in computed radiography (CR) systems. While a conventional radiography automatic exposure control device (AEC) can be calibrated in order to gain a constant optical density on the film independent of beam quality and patient size, CR detectors present a high dynamic range which allows a much larger dose interval, but with different image quality levels. CR leads to a less frequent exam repetition, but may produce quite noisy images if the exposure level on the plate is not correct. The aim of this work is to evaluate the performance of a CR plate (Agfa MD40) in order to optimally calibrate an AEC device. The plate response has been characterised in terms of digital signal, exposure on the plate and signal-to-noise ratio for different beam qualities, in a patient of standard size.

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.

Diamond detector versus silicon diode and ion chamber in photon beams of different energy and field size.

The aim of this work was to test the suitability of a PTW diamond detector for nonreference condition dosimetry in photon beams of different energy (6 and 25 MV) and field size (from 2.6 cm x 2.6 cm to 10 cm x 10 cm). Diamond behavior was compared to that of a Scanditronix p-type silicon diode and a Scanditronix RK ionization chamber. Measurements included output factors (OF). percentage depth doses (PDD) and dose profiles. OFs measured with diamond detector agreed within 1% with those measured with diode and RK chamber. Only at 25 MV, for the smallest field size, RK chamber underestimated OFs due to averaging effects in a pointed shaped beam profile. Agreement was found between PDDs measured with diamond detector and RK chamber for both 6 MV and 25 MV photons and down to 5 cm x 5 cm field size. For the 2.6 cm x 2.6 cm field size, at 25 MV, RK chamber underestimated doses at shallow depth and the difference progressively went to zero in the distal region. PDD curves measured with silicon diode and diamond detector agreed well for the 25 MV beam at all the field sizes. Conversely, the nontissue equivalence of silicon led, for the 6 MV beam, to a slight overestimation of the diode doses in the distal region, at all the field sizes. Penumbra and field width measurements gave values in agreement for all the detectors but with a systematic overestimate by RK measurements. The results obtained confirm that ion chamber is not a suitable detector when high spatial resolution is required. On the other hand, the small differences in the studied parameters, between diamond and silicon systems, do not lead to a significant advantage in the use of diamond detector for routine clinical dosimetry.

Use of TLD in evaluating diagnostic reference levels for some radiological examinations.

The European Council Directive 97/43 introduces diagnostic reference levels (DRL) for all medical examinations involving ionising radiation. Each department has to evaluate patient dose and to compare that value with the DRL adopted by its member state. Italian law, applying the Directive, states that reference levels must be measured every 2 years. Quantities that must be measured are entrance surface dose or air kerma, or other dosimetric quantities. In our work, clinical measurements on patients were made by positioning a thermoluminescence dosemeter (TLD) over the skin of a statistically significant number of patients for each projection of each examination. As there is no national guideline for these measurements in Italy, the aim of this work was to establish a method based both on European publications and on clinical experience. Three different modalities were considered: conventional radiography, computed radiography and mammography. Accordingly, differently shaped types of TLD were required, especially for mammography where the beam energy is lower.

The use of thermoluminescent detectors for measurements of proton dose distribution.

The aim of this work was to investigate the use of TLD-100 detectors in the field of relative dosimetry in proton eye facilities. These dosemeters, of different sizes, were used to measure transverse and longitudinal distributions of 62 MeV unmodulated proton beams at INFN-LNS in Catania. Comparison with other detectors, such as ionisation chambers, GAF and radiographic film, is extensively discussed.

An investigation of the operating characteristics of two PTW diamond detectors in photon and electron beams.

The dosimetric properties of two PTW Riga diamond detectors type 60003 were studied in high-energy photon and electron therapy beam. Properties under study were current-voltage characteristic, polarization effect, time stability of response, dose response, dose-rate dependence, temperature stability, and beam quality dependence of the sensitivity factor. Differences were shown between the two detectors for most of the previous properties. Also, the observed behavior was, to some extent, different from what was reported in the PTW technical specifications. The necessity to characterize each diamond detector individually was addressed.