Breath hydrogen test for lactose absorption capacity: importance of timing of hydrogen excretion and of high fasting hydrogen concentration.

The breath hydrogen (H2) test for lactose absorption capacity is a simple, noninvasive method for the determination of the adult lactase phenotypes, lactose absorber and malabsorber, in healthy subjects. Two breath H2 tests with a load of 50 g lactose monohydrate were performed on 25 healthy adult lactose malabsorbers in order to determine the validity of simplified versions of the test for field studies. A high variability of peak H2 excretion times, rapid changes in breath H2 concentrations and a significant correlation of intraindividual peak H2 excretion times were observed. High fasting excretion of H2 in breath was a frequent cause of misclassification of probands. It is recommended that at least three breath samples per proband should be collected in field studies of lactose absorption and that special diagnostic criteria be applied in classifying subjects with high initial H2 excretion.

Effect of acetylsalicylic acid on symptoms and hydrogen excretion in the disaccharide tolerance test with lactose or lactulose.

Prostaglandins play a role in the pathogenesis of symptoms of food intolerance. An alleviation of lactose intolerance by premedication with the prostaglandin-synthesis inhibitor acetylsalicylic acid (ASA) has been reported. We studied the effect of 900 mg of ASA and of a glucose placebo on disaccharide intolerance symptoms and on breath hydrogen (H2) excretion in 16 healthy adult males 12 of whom were lactose malabsorbers and received 50 g of lactose 30 to 40 min after ASA; the remaining four were lactose absorbers and received 30 g of lactulose. Premedication with ASA had no significant effect on the severity and duration of intolerance symptoms and on the timing of H2 excretion. In contrast, the maximal breath H2 concentration and the total H2 excretion were significantly increased after ASA administration. We conclude that prostaglandins are of minor importance in causing the usually moderate symptoms of disaccharide intolerance. Prostaglandin-synthesis inhibition by ASA may reduce the motility of the colon thereby permitting more colonic gas (derived from unabsorbed carbohydrates) to be absorbed and excreted.

Prevalence of primary adult lactose malabsorption and awareness of milk intolerance in Italy.

A total of 308 healthy Italian adults (192 females, 116 males; mean age 29.2 yr) were examined using a field version of the lactose tolerance test with breath hydrogen determination. Two geographical groups were formed according to the birth places of the probands' grandparents: 208 subjects from northern Italy (mainly from the regions of Piemonte, Lombardia, and Veneto) and 100 probands from Sicily. Lactose malabsorption was diagnosed in 106 subjects in group "north" (51%) and in 71 subjects in group "Sicily" (71%). Awareness of milk intolerance was more frequent in lactose malabsorbers. The incidence of diarrhea after the test dose of lactose was significantly higher in "aware" lactose malabsorbers, when compared with persons of the same group who had not experienced milk intolerance. The significant difference in lactose malabsorption frequency between northern Italy and Sicily is further evidence of a north-south gradient of lactase gene frequencies in Europe.

Population screening for the human adult lactase phenotypes with a multiple breaths version of the breath hydrogen test.

Lactose tolerance tests with conventional blood glucose determination and with breath hydrogen analysis after storage of breath samples in aluminium aerosol cans were simultaneously performed in 60 healthy adult subjects. Both tests were equally reliable in the diagnosis of the lactase phenotype in healthy persons. In subjects with decreased glucose metabolism the breath hydrogen test seems to be more reliable than the blood glucose test. Provisions for storing breath samples for up to several weeks, avoidance of invasive procedures, and insensivity to glucose absorbed during the test make the present version of the lactose tolerance test with breath hydrogen determination particularly suitable for population studies.

Intestinal disaccharidase activities and activity ratios in a group of 60 adult German subjects.

Lactase, maltase and sucrase activities were determined in samples of jejunal mucosa obtained by suction biopsy from 60 healthy adult German males. Primary adult hypolactasia ("lactase deficiency") was found in 8 subjects (13%). Maltase:lactase and sucrase:lactase activity ratios were significantly higher in post-weaning hypolactasia than in adult lactase persistence. Sources of variation in disaccharidase activities measured in biopsy tissue homogenates are discussed.

Prenatal diagnosis of hemoglobin Bart's hydrops fetalis by HPLC analysis of hemoglobin in fetal blood samples.

Since HbF and HbA are not found in fetuses with Hb Bart's hydrops fetalis the feasibility of prenatal diagnosis of homozygous alpha-thalassemia 1 by fetal hemoglobin typing was examined. Blood samples were obtained from fetuses at 18 to 22 weeks of gestation by cordocentesis in 32 pregnant women at risk of having a child with homozygous alpha-thalassemia 1 (alpha-thal-1). The samples were analyzed by a PCR-based method for the diagnosis of alpha-thal-1 (SEA type) and the proportion of hemoglobin fractions were determined by automated HPLC. DNA analysis showed that 8 of the 32 fetuses were homozygotes for alpha-thal-1, 17 were heterozygous for alpha-thal-1 (alpha-thal-1 trait), and a normal complement of four a-globin genes was found in 7 cases. The Hb typing in fetuses with homozygous alpha-thal-1 showed a peak of unbound Hb (Hb Bart's and Hb Portland) and no HbF, HbA and HbA The alpha-thal-1 trait chromatograms showed unbound Hb, pre HbF, HbF and HbA peaks. The chromatogram of normal fetuses showed HbF and HbA peaks without HbA2. In these cases the HbA proportion is between 3% and 10% with no apparent differences between the 18h and 22nd week of gestation. As the analysis of fetal Hb types by HPLC is facile and speedy and the results correspond with those obtained by DNA analysis, fetal Hb typing by automated HPLC is a convenient prenatal diagnostic method for homozygous alpha-thal-1. The method is recommended for prenatal diagnosis in populations with a high frequency of alpha-thal-1.

[Genetic traits in the area of Bodrogköz]. / Genetikai jellegek vizsgálata a Bodrogközben.

In 1984 a late malaria endemic area, called Bodrogköz was studied. This was a reexamination of the population genetic work performed by Walter, Nemeskéri. In six villages of Bodrogköz 328 persons were tested for AB0, Rh blood groups, haptoglobins, haemoglobin concentration, haematocrit, erythrocyte amount, the MCV, the MCH and the G-6-PD were analyzed. The quantitative determination of HbF and HbA2, red cell osmotic resistance and thalassemia were measured as well. Thalassemia heterozygote carriers and an increased level of HbF were revealed. The frequency of G-6-PD deficiency was 0.39%. In Bodrogköz the frequencies of AB0, Rh and haptoglobin types were similar in the present and all previous studies. The background of this similarity might be the genetic similarity between two following generations. On the basis of these facts, the Hb0 Arab and partially DNA work we suggested an alternative hypothesis that these mutant genes got into Bodrogköz by the rather later migration than with ancient Hungarian people during the period of conquest of Hungary.

Gene-dosage effect on intestinal lactase activity demonstrated in vivo.

The activities of the disaccharidases lactase, maltase, and sucrase were determined in upper jejunal biopsies of 65 healthy adult German males. The study was an attempt to demonstrate the gene-dosage effect on lactase activity expected from the presence of a "hypolactasia" (l) and a "lactase-persistence" (L) allele in the German population. In contrast to lactase/sucrase ratios, lactose/maltose ratios showed a trimodal distribution in proportions of presumed genotypes LL, Ll, and ll compatible with Hardy-Weinberg equilibrium. The frequency of homozygotes ll (13.8%) was similar to the average frequency of lactose malabsorbers in Germany reported in the literature. The importance of considering the lactase gene-dosage effect in population studies of lactase activity is discussed.

Prevalence of primary adult lactose malabsorption in Pakistan.

Lactose absorption capacity was examined in 414 apparently healthy, adult Pakistani subjects. In a subgroup of 44 subjects, the lactose tolerance test was performed using both blood glucose and breath hydrogen determination. The remaining 370 probands were examined using a field version of the breath hydrogen test. In the total sample of 414 probands, 248 lactose malabsorbers were identified (60%). This result differs considerably from previous reports of very low frequencies of lactose malabsorption in Pakistan and neighbouring areas.

[Prenatal diagnosis in early pregnancy]. / Zur pränatalen Diagnose in der Frühschwangerschaft.

The scope of prenatal diagnostics of hereditary diseases in early pregnancy and the cooperation of gynaecologists and human geneticists in this field are discussed.

Temporary depression of lactase activity by thyroxine in suckling rats.

The present study was performed in order to clarify controversies concerning the effect of thyroxine on lactase activity in young mammals. Lactase activity was determined in suckling rats with two reference systems (protein and DNA) after one and three thyroxine injections (0.2 mg/100 g body weight). In comparison with control animals lactase activity was decreased after thyroxine administration. The thyroxine effect was dosage-dependent: three injections caused a more profound and prolonged depression of lactase activity. In both thyroxine-treated groups lactase activity returned to age-specific normal levels before the low lactase activity of adult rats was attained. The transient thyroxine-induced changes of lactase activity were similar to the reference parameters protein and DNA.

Ethnic distribution of phenylketonuria in the north German population.

Results of neonatal screening for phenylketonuria (PKU) suggest a west-east gradient of PKU gene frequency in central Europe. In order to test the hypothesis that the unexpectedly high prevalence of PKU in northwestern Germany (northern region of the FRG) is due to the migration of Germans from eastern regions of prewar Germany in the decade after World War II, grandparental origin was determined in a group of 87 pediatric PKU patients and in a control group of 210 children. Grandparents of east German origin were significantly more frequent among the PKU patients. The observed frequency distribution of grandparental subgroups was described by a theoretical distribution in order to obtain a likely set of values for the ratio between the frequency of the PKU gene in the autochthonous populations of prewar northeastern and northwestern Germany. The most likely value for the PKU gene frequency ratio was 1.37, which indicates that the prevalence for PKU in prewar northeastern Germany was almost twice as high as in the autochthonous population of the northwest.

Distribution of adult lactase phenotypes in the Tuareg of Niger.

The adult lactase phenotype, lactose absorber or malabsorber, was determined using the lactose tolerance test with breath hydrogen assay in a group of Tuareg, a traditionally nomadic pastoralist population in the central Sahara. Out of a total of 118 subjects, 103 (87.3%) were lactose absorbers and 15 (12.7%) lactose malabsorbers. The frequency of the "lactase suppression gene" in this population sample was .357 (SD .043). The low frequency of lactase suppression in the Tuareg supports the hypothesis of natural selection in favor of the "lactase persistence gene" in milk-dependent nomadic pastoralist.

Lactose absorption and malabsorption in healthy German children: improved phenotypic resolution by simultaneous determination of breath hydrogen and carbon dioxide.

A total of 124 apparently healthy German children aged 8 to 10 years were examined for lactose absorption employing the breath hydrogen test with multiple breath collection. Analysis of the maximal change of breath hydrogen concentration (delta maxH2) 110 and 150 min after a lactose load of 30 g failed to yield a bimodal distribution separating lactose absorbers and malabsorbers as observed in adults. Comparison with an adult control group of 120 subjects showed that the mean CO2 concentration was significantly lower and the coefficient of variation was considerably higher in the breath samples of the children. The difference between the highest and the lowest CO2 concentration in the three samples obtained from each individual was also significantly higher in the group of children. Normalizing the children's H2 concentration values to the mean CO2 concentration in the total group (3.04%) yielded a bimodal distribution of the delta maxH2 values. Of 124 children, 18 were identified as lactose malabsorbers. The 14.5% frequency is similar to that observed in German adults.

Population screening for beta-thalassaemia.

The graphic recording of time to 50% haemolysis in a glycerine-saline solution is a simple, reproducible method of determining erythrocyte osmotic fragility. Studies on a normal population yielded an upper limit of normal of 90 s. In 250 healthy males from Northern Thailand all 19 with beta-thalassaemia minor had abnormal osmotic indices, and the value of the test was confirmed in beta-thalassaemia heterozygotes in Europe. Of 23 patients with iron deficiency 18 had abnormal osmotic indices. However, this is not thought likely to be a significant source of false positives in the screening of populations at risk of haemoglobinopathies but in whom iron deficiency is rare.