Quality control study of H2 breath testing for the diagnosis of carbohydrate malabsorption in Italy. The "Tenue Club" Group.

BACKGROUND AND AIMS: H2 breath testing is increasingly used in Italy. The aim of this multicenter study was to assess the accuracy of this technique in the diagnosis of carbohydrate malabsorption. METHODS: An anonymous questionnaire was used to collect information about H2 breath testing methods and to design the quality control study. Fifteen out of 23 laboratories responded to the questionnaire and 12/23 completed the entire study. RESULTS: The survey revealed that a large variety of H2 testing methods are employed in Italy, but none have been previously tested for accuracy. This prospective study showed that these tests fail to identify > 20% of patients with malabsorption. In contrast, a new method based on single H2 breath measurement at 6 hours after lactulose ingestion and a cutoff value of greater than 5 ppm, had a sensitivity of 92% +/- 4% and a specificity of 94% +/- 0.5%. Increasing the cut-off to 10 ppm resulted in a sensitivity of 88% +/- 9% and a specificity of 100%. This improved accuracy was obtained with a much simpler testing procedure in which only one breath sample is analyzed, in contrast to the baseline and multiple subsequent samples that are analyzed using the currently employed techniques. CONCLUSIONS: A great improvement in the accuracy of the H2 breath test, as well as a considerable saving in terms of time and costs, may be possible through the use of a new, simplified H2 breath test followed by careful H2 analysis.

Magnetic transcranial stimulation in healthy humans: influence on the behavior of upper limb motor units.

Aim of the study was to analyze the characteristics of motor action potentials recruitment during magnetic trans-cranial stimulation (TCS) of the brain. Coaxial needle recordings from hand and upper limb musculature, as well as surface electrodes were employed in 20 healthy controls during magnetic TCS with regular and figure-of-8 coil in different experimental protocols including: (a) simple reaction time paradigm during which TCS at subthreshold intensity for eliciting MEPs in relaxation was delivered at various intervals between the signal to move and the onset of the voluntary EMG burst; (b) suprathreshold TCS was randomly delivered while the subject was voluntarily firing at a regular rate one 'low' and/or 'high threshold' motor unit action potential (MUAP). The pre- and post-TCS MUAPs recruitment as well as their firing rates were compared; (c) recordings with two separate needles picking up individual MUAPs from the same or from two different muscles were obtained in order to test 'synchrony' of MUAP's discharge before and after TCS; (d) the influence of the time-interval separating the last discharged MUAP from TCS was evaluated. (e) differences between simultaneous surface and depth recordings were examined. The following results were obtained. (a) The same low-amplitude MUAP which is first voluntarily recruited at the onset of the EMG burst is the one initially fired by TCS in the pre-movement period. Latency shortenings and amplitude enlargement of surface MEPs were observed with faster reaction times. Such changes were coupled to the recruitment of high-threshold MUAPs being larger in amplitude and briefer in latency than the initial one. (b) When using suprathreshold TCS, MEPs followed by silent periods were found. The SP was followed by a rebound acceleration of the MUAPs firing rate compared with pre-TCS levels. Besides rebound acceleration, new MUAPs of larger amplitude than the original (= pre-stimulus) ones were recruited beyond the voluntary control. This phenomenon-together with longer SPs- was progressively more pronounced with stronger stimuli. (c) TCS was affecting the 'synchrony' of MUAPs. (d) If the latency difference between the last pre-stimulus spike and the TCS was exceeding the half-cycle of the MUAP 'natural' firing, the SP was longer in duration. (e) SPs not preceded by MEPs were clearly present in depth recordings. Surface recordings mainly reflected the behavior of high-threshold and large MUAPs.

Lactulose hydrogen breath test in orocecal transit assessment. Critical evaluation by means of scintigraphic method.

Orocecal transit time can be studied easily using the hydrogen breath test with lactulose, but the method has some important limitations. The orocecal transit time of 10 patients suffering from irritable bowel syndrome was measured twice, at a one-week interval, by breath test and scintigraphy simultaneously using an aqueous solution of 20 g lactulose containing 74 MBq of [99mTc]DTPA. Abdominal radioactivity and alveolar hydrogen values obtained every 5 min were noted and used to obtain the following: orocecal transit time by the two methods; ileocecal lactulose flow; total and per gram of lactulose hydrogen production; mean hydrogen concentration during the right colon filling; and measurement error of the breath test with respect to the scintigraphy. In the case of the breath test, the orocecal transit time intrapatient reproducibility was better (coefficient of variation = 13.5%) when a hydrogen threshold increment of 5 ppm was used; the best correlation with the scintigraphic measurement was observed at this threshold (r = 0.90, P < 0.001). The breath test overestimated orocecal transit time with the error correlating negatively and significantly with the total hydrogen production and, particularly, the mean hydrogen concentration (r = 0.79, P < 0.01): for a mean hydrogen concentration of more than 15 ppm, the error was negligible, while within this value there was a noticeable overestimation. To conclude, the lactulose hydrogen breath test is capable of giving an accurate measurement of orocecal transit time if a hydrogen threshold increment of 5 ppm is chosen and if the mean hydrogen concentration in the first 30 min of the right colon filling is taken into account.

Absence of histopathological changes of ileum and colon in functional chronic diarrhea associated with bile acid malabsorption, assessed by SeHCAT test: a prospective study.

OBJECTIVES: Chronic diarrhea of unknown origin is often associated with bile acid malabsorption, the pathogenetic role of which is uncertain. The aim of this study was to identify morphological abnormalities in the ileal and colonic mucosa in patients with this disorder. METHODS: We performed a prospective and blinded histopathological study (between June 1991 and November 1992) of endoscopic biopsies of the distal ileum and colon of 23 patients suffering from chronic diarrhea of unknown origin. In 14, the SeHCAT (75-selena-homo-cholic acid taurine) test was abnormal owing to bile acid malabsorption; in the other nine, the diarrhea control group, the test results were normal. A detailed evaluation of surface epithelium, immune response and inflammatory changes was made. RESULTS: in two patients and two controls, mild villous atrophy was observed; there was also slight inflammation of the ileal and colonic mucosa occurring with the same frequency in both groups. A slight replacement of goblet cells was more evident in the diarrhea control group. CONCLUSIONS: Chronic diarrhea of unknown origin associated with bile acid malabsorption does not involve specific morphological changes of ileal or colonic mucosa, and its pathogenesis must be looked for in dysfunction of the ileum and/or colon.

Bile acid malabsorption in AIDS-associated chronic diarrhea: a prospective 1-year study.

OBJECTIVES: In patients with chronic diarrhea associated with acquired immunodeficiency syndrome, bile acid malabsorption, very rarely investigated, may have an important pathogenetic role. METHODS: In this 1-yr prospective study, 15 patients with AIDS-associated chronic diarrhea and 10 AIDS-controls were studied for bile acid malabsorption by means of the SeHCAT abdominal retention test. The patients with diarrhea underwent the glucose hydrogen breath test to identify any bacterial proliferation in the small bowel. RESULTS: In the chronic diarrhea group, only one case of small bowel bacterial overgrowth, and seven cases (47%) with generally severe bile acid malabsorption, were observed. Among the controls, only one had an abnormal low SeHCAT retention. In both cases with Cryptosporidium infection, the SeHCAT test was pathological. CONCLUSIONS: These data are of clinical importance for the pathogenetic study of AIDS-associated chronic diarrhea and for specific treatment with cholestyramine.

Technetium-99m hexamethyl propylene amine oxime granulocyte scintigraphy in Crohn's disease: diagnostic and clinical relevance.

Scintigraphy with autologous granulocytes labelled by technetium-99m hexamethyl, propylene amine oxime (99mTc-HMPAO) was performed in 103 Crohn's disease patients and 52 healthy controls. In 31 patients endoscopic and histologic activity was compared with scan activity index. In the 98 patients with a positive scan, the extent of Crohn's disease, assessed by scintigraphy, was compared with that evaluated by small bowel x ray or colonoscopy with biopsies. In 48 patients, Crohn's disease activity index, activity index, simple index, erythrocyte sedimentation rate, C-reactive protein were correlated with the scan results. In 16 patients the five parameters and scan were repeated after treatment with methyl-prednisolone (10 cases), enteral nutrition (3), and 5-acetylsalicylic acid (3). The results showed that 99mTc-HMPAO granulocyte scan had a 95% sensitivity and 100% specificity to detect active inflammation; it correctly showed an abscess or a fistula in all the 24 cases found. The correlation between histological inflammatory activity and scan activity index was highly significant (r = 0.85; p < 0.01), less significant (r = 0.65; p < 0.01) between endoscopy and scan activity index. The evaluation for the extent of Crohn's disease by scan was completely correct in the small bowel (100%) and 93% correct in the large bowel. No correlation was seen between the three clinical activity parameters and scanning; in more than 80% of the cases in remission on the basis of a clinical or laboratory index, scintigraphy remained positive. Medical treatment was effective on the clinical indices but not on the active inflammation in the ileum, whereas it led to a negative scan in 5/11 cases in the large intestine. Scintigraphy with 99mTc-HMPAO granulocyte plays an important part in Crohn's disease for the diagnosis of complications, for activity and assessment of the extent, and for the treatment results evaluation.

Scintigraphic study of gastrointestinal transit and disintegration sites of mesalazine tablets labeled with technetium-99m.

Tablets of mesalazine covered with a pH-dependent coating (Pentacol), labeled by an original technique with technetium-99m, were administered to 12 patients, 9 with Crohn's disease, 3 of which recurrent, 1 with ulcerative colitis, and 2 with irritable bowel syndrome, with the aim of verifying in vivo the intestinal site of disintegration and how the contents spread throughout the intestine. In all cases the tablet was broken down in the distal ileum at extremely variable intervals, from 5 to 27 h, and the contents spread into the nearby loops and into the colon. The notable differences in the residence time of the whole tablet in the ileum can be explained by differences in adhesion to the inflamed mucosa and by a lower pH in the part of the ileum affected by the disease.

Post-cholecystectomy diarrhea: evidence of bile acid malabsorption assessed by SeHCAT test.

Although bile acid malabsorption (BAM) in post-cholecystectomy diarrhea (PCD) is a well-known clinical condition, its true etiopathogenetic role is not entirely clear. The SeHCAT (23-selena-25-homotaurocholic acid) test, a simple and reliable BAM test, was performed in 33 cholecystectomized patients, 26 with chronic diarrhea. The test revealed a marked degree of BAM in 25/26 cases. Cholestyramine in doses of 2-12 g/day was effective in 23/25, ineffective in two, and was not tolerated in one patient. When treatment was suspended, diarrhea recurred in nine, whereas bowel habit remained regular in 60%, with brief sporadic episodes of diarrhea in the other cases. The SeHCAT test was repeated in 11 cases after cholestyramine treatment interruption, and revealed the normalization of parameters in two patients and an improvement in three. We conclude that BAM is an important etiopathogenetic factor in PCD that responds favorably to cholestyramine. In 60% of the cases, it resolved diarrhea definitively, although without eliminating BAM in all cases: this suggests that existence of other factors associated with BAM. The SeHCAT test is essential for a differential diagnosis between PCD and the irritable bowel syndrome.

Dynorphin B-like immunoreactivity in gastroduodenal biopsy specimens from gallstone patients.

Dynorphin B-like immunoreactivity (ir-dyn B) was measured by a validated radio-immunoassay in gastroduodenal biopsy specimens from control and gallstone patients. Levels were significantly lower in acetic acid extracts of specimens of the transverse portion of the duodenum from gallstone patients. Gel permeation chromatography showed that almost all ir-dyn B in duodenal samples corresponded to a molecular form co-eluting with authentic dyn B. Duodenal extracts from gallstone patients had less of this form. Reverse-phase high performance liquid chromatography of the pooled gel chromatography fractions showed up a molecular form with the same retention time as synthetic dyn B which was significantly less in fractions from duodenal extracts of gallstone patients. These results indicate the occurrence of dyn B in the human gastrointestinal tract; however, at this stage of our understanding, no causal relationship can be demonstrated with functional alterations of the biliary tree.

[Primary intrahepatic lithiasis]. / La lithiase intra-hépatique primitive.

Isolated intrahepatic lithiasis is a very rare condition in western countries; the reported case has to be added to the 29 cases described to date in the literature. The pathogenesis of this disease is unknown; physical and chemical bile alterations favouring lithogenesis is the most reliable hypothesis. In this case the Roux-en-Y hepaticojejunostomy with cutaneous stoma allowed us to perform periodic cleaning of intrahepatic bile ducts until complete elimination of all stones.

[Primary intrahepatic lithiasis]. / La lithiase intra-hépatique primitive.

Isolated intrahepatic lithiasis is a very rare condition in western countries; the reported case has to be added to the 29 cases described to date in the literature. The pathogenesis of this disease is unknown; physical and chemical bile alterations favouring lithogenesis is the most reliable hypothesis. In this case the Roux-en-Y hepaticojejunostomy with cutaneous stoma allowed us to perform periodic cleaning of intrahepatic bile ducts until complete elimination of all stones.

Description and evaluation of a method for computer analysis of the exercise electrocardiogram.

The new approach to computer processing of exercise electrocardiography has been made easier by the development of microcomputers. Studies are necessary to validate analyzed electrocardiographic data for the diagnosis of ischemia. We describe and assess in this paper a new program for the analysis "on line" of 12 leads during effort. The program detects "normal QRS" and ectopic beats. Amplitude of R wave, length of QRS, ST level after a programmable delay from J point, ST maximal slope and amplitude of T wave are calculated and recorded every 15 sec in the 12 leads. In 200 exercise stress tests quantitative data provided by the processor were compared with visual analysis and with clinical data. ST level less than or equal to -0.8 mm and ST slope less than or equal to 1.2 mV/sec or ST level greater than or equal to +2.0 mm and ST slope less than or equal to 0.6 mV/sec were the best analyzed criteria for ischemia. Using these criteria, sensitivity increased from 86.6% by visual reading to 92% by computer analysis, without change in specificity (94%).

75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit.

The purpose of this study was to evaluate whether bile acid malabsorption assessed by the 75SeHCAT test, had a pathogenetic role in functional chronic diarrhoea and to ascertain whether the small bowel transit time (SBTT) could be correlated with the 75SeHCAT test results. The test was based on the counting of the abdominal retention of a 75-selenium labelled homotaurocholic acid. The 75SeHCAT test was carried out in a control group of 23 healthy adults and in 46 patients, 38 of whom were suffering from irritable bowel syndrome (IBS) of diarrhoeic form and eight patients who had undergone cholecystectomy and were suffering from chronic diarrhoea. Faecal bile acid loss was determined in nine patients, and in 14, serum bile acid increase after a standard meal was measured. In 17, SBTT was studied by hydrogen breath test after lactulose administration (21 g in 300 ml water). In 15 patients, choledochocaecal transit time was estimated by Tc99m-HIDA (111 MBq) cholescintigraphy. In 20 of 46 subjects, 75SeHCAT retention was below normal level, and in 19 cholestyramine administration relieved diarrhoea. 75SeHCAT results were related to faecal bile acid loss, while no correlation was found with serum bile acids and SBTT. The data suggest a possible wider use of the 75SeHCAT test in chronic diarrhoea to estimate bile acid malabsorption in irritable bowel syndrome, diarrhoeic form, and provide an effective treatment. In our patients small bowel transit velocity does not seem to be a pathogenetic factor of bile acid malabsorption.

Scintigraphic evaluation of enterogastric reflux using 75Se-HCAT: methodology and first clinical observations.

The aim of this study was to assess the possibility of detecting enterogastric reflux (EGR) by 75Se-HCAT cholescintigraphy. The lowest detectable activity in the gastric area at different concentrations of the radiotracer in the gallbladder was preliminary measured both in a plastic phantom and in an in vivo model. Ten patients were studied after a single oral administration of 1480 KBq 75Se-HCAT. Gamma camera imaging was carried out for five consecutive days during both fasting and after meal ingestion. In our in vivo model an EGR corresponding to 1% of gallbladder content on day one and 8% on day five was detected. In three out of five patients in whom bile was present in the stomach at endoscopy, 75Se-HCAT cholescintigraphy demonstrated an EGR, while in three out of five patients in whom endoscopy was negative, 75Se-HCAT cholescintigraphy detected EGR either during fasting or after meal ingestion. As EGR is not constant, 75Se-HCAT may be a useful tracer of bile to detect EGR over a prolonged period of time and in different physiological conditions.

Use of 23-selena-25-homocholyltaurine to detect bile acid malabsorption in patients with illeal dysfunction or diarrhea.

Abdominal gamma-counting after oral administration of 23-selena-25-homocholyltaurine (75SeHCAT) was carried out on 23 healthy volunteers and 66 patients: 33 with distal ileum resections, 3 with Crohn's disease of the ileum, 17 suffering from various intestinal diseases but with normal ileum, and 13 with chronic diarrhea syndrome but without evident intestinal or extraintestinal pathology. The percentage value of 75SeHCAT abdominal retention was assessed by analysis of the activity versus time curve, obtained by single exponential least-squares fit in five consecutive measurements (time zero and 1, 3, 5, and 7 days after 75SeHCAT administration) and directly by the gamma-camera countings on days 3, 5, and 7. The percentage values obtained from the curve on the third day were found to be the most suitable for differentiating between the groups, giving the 75SeHCAT test a 94% sensitivity and a 100% specificity. Our data show that this test is a valid indicator of bile acid loss: actually, it gave evidence of idiopathic malabsorption of bile salts in 6 patients with diarrhea of unknown origin who responded to cholestyramine and showed a correlation (correlation index = 0.585) with the residual ileum of the last meter in resected patients. Moreover, the 75SeHCAT test is easy to perform in any hospital with gamma-counting facilities and has negligible radiation risk.

ERCP pneumatic injector. A new tool in radiation exposure prevention for personnel.

A new tool to aid radiation exposure prevention is presented. The ERCP pneumatic injector, which may be used by the endoscopist by actuating a foot-operated starting system, is capable of injecting the contrast medium at the desired flow and pressure, which can be adjusted during the examination. In this way, personnel radiation risk is eliminated.

Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis.

Lactose malabsorption was studied, by hydrogen breath test, in 72 adults suffering from irritable bowel syndrome, in 20 ulcerative colitis patients, and in 69 healthy subjects. The minimum dose of lactose required to cause a positive breath test was determined, and the symptoms caused and the resulting hydrogen eliminated quantified. A high incidence of lactose malabsorption was shown at standard doses (up to 50 g) in both the healthy subjects (70%) and the patients (86% and 85%, respectively). In the irritable bowel syndrome and the ulcerative colitis groups, symptoms occurred with a smaller quantity of breath hydrogen, presumably in association with a greater individual sensitivity of the colon to distension. The threshold lactose dose was notably lower in the diseased subjects who registered as evidence a prevalence of malabsorption at a 20-g lactose load. The pathogenetic role of lactose malabsorption in the irritable bowel syndrome is emphasized, as is the importance of the personal lactose tolerance.