Anna Kasicka-Jonderko

Feasibility of a breath test with a substrate of natural 13C-abundance and isotope-selective non-dispersive infrared spectrometry: A preliminary study

Background and Aims:  Isotope‐selective non‐dispersive infrared spectrometry (NDIRS) is a cheaper alternative to isotope ratio mass spectrometry (IRMS). We checked on the efficiency of NDIRS to perform a breath test with naturally 13C‐enriched maize starch.

How reproducible is cutaneous electrogastrography? An in-depth evidence-based study1

Abstract  Aim:  To check on reproducibility of parameters of the cutaneous electrogastrogram registered at a close or a distant time span.

Effect of nifedipine on interdigestive gallbladder volume and postprandial gallbladder emptying in man

The effect of two oral doses (10 and 20 mg) of nifedipine versus placebo on the fasted gallbladder volume and on the meal-induced gallbladder emptying was assessed according to a double-blind study protocol in 12 healthy volunteers. Eight subjects underwent three studies (with placebo and with both nifedipine doses), whereas in two subjects the effect of a 10-mg nifedipine dose, vs placebo and in two others the effect of a 20-mg nifedipine dose vs placebo was examined. The studies were performed on separate days, and the gallbladder volume was measured by means of real-time ultrasonography. Neither placebo nor 20 mg nifedipine per os elicited any significant change in the fasted gallbladder vlume. With 10 mg nifedipine per os a significant increase in the interdigestive gallbladder volume was observed: 22.9±2.9 cm3 before and 26.2±3.2 cm3 after the drug receipt (P<0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipineper os without, however, reaching the level of statistical significance. Following 20 mg nifedipineper os, a marked delay in the meal-stimulated gallbladder emptying occurred as reflected by a decrease in the gallbladder ejection fraction from 48.1±4.5% (placebo) to 26.4±5.0% (nifedipine) (P<0.02) at 30 min and from 54.0±3.6% (placebo) to 33.2±4.6% (nifedipine) (P<0.02) at 40 min after the test meal. We conclude that a therapeutic oral dosage of nifedipine has a significant relaxing effect on the human gallbladder.

13C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

AIM To find the most reproducible quantitative parameter of a standard (13)C-methacetin breath test ((13)C-MBT). METHODS Twenty healthy volunteers (10 female, 10 male) underwent the (13)C-MBT after intake of 75 mg (13)C-methacetin p.o. on three occasions. Short- and medium-term reproducibility was assessed with paired examinations taken at an interval of 2 and 18 d (medians), respectively. RESULTS The reproducibility of the 1-h cumulative (13)C recovery (AUC(0-60)), characterized by a coefficient of variation of 10%, appeared to be considerably better than the reproducibility of the maximum momentary (13)C recovery or the time of reaching it. Remarkably, as opposed to the short gap between consecutive examinations, the capacity of the liver to handle (13)C-methacetin increased slightly but statistically significantly when a repeat dose was administered after two to three weeks. Regarding the AUC(0-60), the magnitude of this fixed bias amounted to 7.5%. Neither the time gap between the repeat examinations nor the gender of the subjects affected the (13)C-MBT reproducibility. CONCLUSION (13)C-MBT is most reproducibly quantified by the cumulative (13)C recovery, but the exactitude thereof may be modestly affected by persistent stimulation of CYP1A2 on repeat examinations.

Interference of acute cigarette smoking with [13C]methacetin breath test

It is essential to establish whether and how environmental factors affect the reliability of [13C]methacetin breath test (13C-MBT). In 12 healthy volunteers (smokers), a standard 13C-MBT with 75 mg [13C]methacetin was performed twice in random order: on a control day without smoking and on another day with smoking two cigarettes antecedently. A considerable flattening of the curve of the momentary 13C recovery within the expiratory air was observed when the 13C-MBT was performed after smoking. The maximum of the momentary 13C recovery, D max, decreased from 37.20±2.58 to 25.39±2.29% dose/h (p=0.00052). Moreover, the time to reach D max was prolonged after cigarette smoking (26.5±3.1 vs. 16.5±1.9 min, p=0.0199). The curve of the cumulative 13C recovery on the cigarette smoking day appeared to be shifted downwards, and statistically significant differences relative to the control situation were found between the 24th and 75th minute following [13C]methacetin administration. Smoking cigarettes immediately prior to the 13C-MBT diminishes the ability of the liver to handle methacetin, and hence a possibility of such an interaction should be excluded in order to interpret the results of the test correctly.

Exact profiles of 13CO2 recovery in breath air after per oral administration of [13C]methacetin in two groups of different ages

The aim of this study is to determine if age is a factor influencing the results of a [13C]methacetin breath test (13C-MBT). Two groups of healthy volunteers, each comprising six men and six women, but differing in average age (Y=young, 25.1±0.6 years, MA=middle-aged;, 46.0±2.1 years) orally took 75 mg [13C]methacetin. Samples of expiratory air for 13CO2 measurement were collected up to 48 h after intake of the substrate. A maximum momentary 13CO2 breath exhalation of 37.0±2.6%dose/h was observed at 18 min (median, range: 9–30 min) in the young subjects and of 38.4±2.5%dose/h at 18 min (median, range: 12–30 min) in the middle-age volunteers. The cumulative 13C elimination in expiratory air was statistically significantly higher in the MA compared with the Y group as from 75 min up to 180 min, indicating a greater microsomal metabolic efficiency of the liver in the middle-aged healthy subjects. Gender, use of hormonal contraception, cigarette smoking, or body mass index did not modify the age-related effect on the cumulative 13C elimination in breath air. The study results imply a necessity of composing control groups well matched with regard to the age structure for a proper interpretation of clinical 13C-MBT results.

Effect of single-dose administration of recombinant interferon-alpha2b on gastric myoelectrical activity in patients with chronic hepatitis C.

BackgroundUpper abdominal complaints during interferon therapy may result from impaired gastric motility and/or evacuatory function. We examined the effect of acute administration of interferon on gastric myoelectrical activity (GMA) with the use of surface electrogastrography.MethodsThe study population comprised 25 patients with chronic hepatitis C. All of them were naïve to interferon. On 2 days, after a 25-min basal GMA registration, in group A (5 men, 7 women, aged 44.3 ± 2.8 years) placebo or 5 million i.u. recombinant interferon alpha-2b (IFNA) was administered s.c. and the GMA was recorded in the interdigestive state for two periods (2 h and 4 h), separated by a 15-min break. In group B (7 men, 6 women, aged 44.7 ± 3.9 years) placebo or 5 million i.u. IFNA was injected s.c. after the ingestion of a semiliquid test meal of 364 kcal. Subsequently, the postprandial GMA was recorded for two periods (2 h and 4 h), separated by a 15-min break.ResultsA typical flu-like syndrome was observed in 91.7% of patients in group A, and in 92.3% of patients in group B, thus providing evidence of the pharmacodynamic efficiency of the IFNA administration. In the fasted state, IFNA brought about a negligible increase in the rhythmicity and power of the gastric slow waves. IFNA did not elicit any statistically significant effect on gastric slow-wave activity postprandially.ConclusionsAcute administration of interferon does not involve any deterioration of GMA that could be linked to the previously reported upper abdominal symptoms in patients undergoing treatment with this drug.

Impact of combined oral contraceptives containing ethinylestradiol on the liver microsomal metabolism

Abstract Objectives To check whether currently used combined oral contraceptives (COCs) containing ethinylestradiol (EE) affect the liver microsomal metabolism. Methods 13C-methacetin breath test (13C-MBT) – a sensitive non-invasive probe of cytochrome P-450 1A2 activity – was performed in 15 women on day 14, 15, 16, 17 or 18 of intake of their COC (containing EE), and between day 1 and 5 during the withdrawal bleeding, as well as in nine women not using hormonal contraception during the luteal phase of their cycle (between the 17th and the 23rd day), and between day 1 and 5 during menstruation. Results The maximum breath 13C elimination was significantly lower during the phase of intake of contraceptive pills than during withdrawal bleeding: 31.5 ± 2.2 %/h vs. 38.2 ± 1.9 %/h (p = 0.0045), whereas the time to reach it was similar on the two study days: 21.2 ± 1.2 min vs. 21.0 ± 1.1 min. Between the 27th and the 180th min of observation the cumulative breath 13C elimination was statistically significantly lower during intake of the pill than during withdrawal bleeding. No significant menstrual cycle phase-dependent fluctuations in the results of the 13C- methacetin breath test were observed in the control group. Conclusion COCs containing EE markedly inhibit hepatic microsomal function. This phenomenon must be taken into consideration when interpreting results of 13C-MBT.

Unreliability of Breath Methane as a Candidate Indicator of Functional Bowel Disorders

BACKGROUND/AIMS The aim of this study was to examine the reproducibility of methane and hydrogen in exhaled air breath after a per-oral load of lactulose. METHODS Methane was present in the exhaled breath of 21 of 50 healthy subjects recruited by advertisement. Three methane breath tests were performed in 12 women (aged 23.6+/-0.5 years, mean+/-SEM) after they consumed 10 g of lactulose dissolved in 300 ml of water. Short- and medium-term reproducibilities were assessed by paired examinations taken 3 and 17 days (median) apart, respectively. RESULTS High values of coefficients of variation for paired examinations (CV(p)) indicated a poor short-term reproducibility of parameters characterizing either the methane or hydrogen excretion in breath air: CV(p) values of the maximum net increments over baseline in methane (max CH(4_net)), and in hydrogen (max H(2_net)), were 34% and 41%, respectively. Moreover, the reproducibility consistently deteriorated with increasing time gap between repeat measurements (CV(p): 60% for max CH(4_net) and 64% for max H(2_net)). CONCLUSIONS The low reproducibility of parameters characterizing quantitative methane breath excretion suggests that caution is necessary when judging the clinical usefulness of the methane breath test after a per-oral lactulose load for the purpose of diagnosing and classifying functional bowel disorders.

Comparison of two dosage regimens of the substrate for the [13C]methacetin breath test

The [13C]methacetin breath test ([13C]MBT) – a valuable non-invasive tool dedicated to the assessment of the liver metabolic capacity – still needs standardisation. The aim of this study was to check whether currently used dosage regimens of [13C]methacetin provide concordant [13C]MBT results in subjects with an atypical body constitution. Healthy volunteers: low body mass<55 kg (eight women), and high body mass>95 kg (eight large body frame men) were recruited. They underwent [13C]MBT on separate days, taking in random order [13C]methacetin: a fixed 75 mg dose (FX75), or a 1 mg kg−1 body mass-adjusted dose (BMAD). Samples of expiratory air for 13CO2 measurement were collected over 3 h. The maximum momentary 13C elimination in breath air occurred earlier and was higher following BMAD than with FX75 in the low body mass females (T max 14.6±1.0 min vs. 22.1±2.4 min, p=0.019; D max 41.9±2.9 % dose h−1 vs. 36.6±3.6 % dose h−1, p=0.071). In the high body mass men, T max remained unchanged, whereas D max was slightly higher with BMAD compared to FX75 (21.5±3.2 min vs. 23.0±3.0 min; 38.5±2.9 % dose h−1 vs. 32.3±2.5 % dose h−1). It is concluded that in subjects with a body constitution outside the general population average, the dosage of the substrate may affect some results of the [13C]MBT. The dosage-related differences appear, however, to be insignificant if the result of the [13C]MBT is reported as a cumulative 13C recovery in breath air.