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Biomedical subjects

M P Roth

Publications and source records attributed to M P Roth.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of esophageal acid exposure at 1 cm and 6 cm above the squamocolumnar junction using the Bravo pH monitoring system.

The aim of this study was to assess the quantitative differences of acid exposure at 1 cm and 6 cm above the squamocolumnar junction (SCJ) using two radiotelemetry pH capsules affixed to the esophageal mucosa. Ten normal subjects and 10 endoscopy-negative gastroesophageal reflux disease (GERD) patients without hiatus hernia (ages 20-54, 12 male) were studied for a 24-h period using the Bravo pH monitoring system. pH capsules were placed 1 cm and 6 cm above the SCJ. Interpretable data for at least 14 h was obtained in 18 of the 20 subjects (9 normal, 9 GERD). Two failures occurred secondary to early capsule dislodgement. Median esophageal acid exposure was significantly increased at 1 cm above the SCJ compared to 6 cm above the SCJ during the total, upright and postprandial time periods in both normal and GERD subjects. During a 2 h postprandial period the esophageal acid exposure was 8-fold greater in GERD subjects and 5-fold greater in normal subjects 1 cm above the SCJ compared to 6 cm above the SCJ. Confident measurement of esophageal acid exposure at a fixed position 1 cm above the SCJ is feasible with the Bravo system. Acid exposure was significantly higher 1 cm above the SCJ compared to 6 cm above the SCJ in both GERD patients and controls. These findings suggest that measurement of acid exposure 1 cm above the SCJ may improve accuracy of pH monitoring by detecting acid reflux events confined to the distal esophagus.

Adult↗
PubMed2005

Acid reflux event detection using the Bravo wireless versus the Slimline catheter pH systems: why are the numbers so different?

OBJECTIVE: This study analysed the relative accuracy of the Bravo wireless and the Slimline catheter-Mark III Digitrapper pH systems in the detection of acid reflux events. METHODS: Twenty five asymptomatic subjects were studied. A Bravo capsule was placed 6 cm above the squamocolumnar junction (SCJ), marked by an endoclip, and a Slimline pH catheter was placed 5 cm above the manometrically localised lower oesophageal sphincter. The distance between the SCJ and each pH electrode was measured fluoroscopically. An in vivo pH reference was established using swallows of orange juice (pH 3.88). Concurrent pH data from the two systems were analysed in Excel spreadsheets. RESULTS: Significantly more acid reflux events were reported by the Digitrapper system than the Bravo system (117.0 v 41.8). This was not explained by electrode position as there was no difference in median distance between the SCJ and either pH electrode (7.25 cm v 7.08 cm). The dominant source of discrepancy between systems was inaccuracy in electrode calibration and, after adjustment using the in vivo orange juice pH measurement, the discrepancy improved by 40%. However, discrepancy still existed and was most pronounced with short reflux events (1-15 s for the catheter, 1-17 s for the Bravo) associated with minimal intraoesophageal acidity and poor concordance between systems. CONCLUSION: Substantially more reflux events were reported by the Digitrapper system compared with the Bravo system; 40% of excess events were attributable to a flawed software scheme for electrode thermal calibration while most of the remainder were brief events with poor reproducibility between systems.

Adult↗
PubMed2002

Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice.

BACKGROUND: Although much progress has been made recently in characterising the proteins involved in duodenal iron trafficking, regulation of intestinal iron transport remains poorly understood. It is not known whether the level of mRNA expression of these recently described molecules is genetically regulated. This is of particular interest however as genetic factors are likely to determine differences in iron status among mouse strains and probably also contribute to the phenotypic variability seen with disruption of the haemochromatosis gene. AIMS: To investigate this issue, we examined concomitant variations in duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), hephaestin, stimulator of Fe transport (SFT), HFE, and transferrin receptor 1 (TfR1) transcripts in response to different dietary iron contents in the four mouse strains C57BL/6, DBA/2, CBA, and 129/Sv. SUBJECTS: Six mice of each strain were fed normal levels of dietary iron, six were subjected to the same diet supplemented with 2% carbonyl iron, and six were fed an iron deficient diet. METHODS: Quantification of mRNAs isolated from the duodenum was performed using real time reverse transcription-polymerase chain reaction. RESULTS: There was a significant increase in mRNA expression of Dcytb, DMT1, FPN1, and TfR1 when mice were fed an iron deficient diet, and a significant decrease in mRNA expression of these molecules when mice were fed an iron supplemented diet. Strain to strain differences were observed not only in serum transferrin saturations, with C57BL/6 mice having the lowest values, but also in hepatic iron stores and in duodenal mRNA expression of Dcytb, DMT1, FPN1, hephaestin, HFE, and TfR1. CONCLUSIONS: The results favour some degree of genetic control of mRNA levels of these molecules.

Animals↗
PubMed2000

Genetic markers of immunoglobulins and diabetes mellitus in the multiracial population of New Caledonia. The CALDIA Study Group.

GM and KM immunoglobulin allotypes, which are the markers, respectively, of the constant parts of the heavy and the light chains of the IgG1, IgG2 and IgG3 subclasses, have been analysed in diabetic mellitus patients and controls living in New Caledonia. We tested 40 Europeans, 256 Melanesians and 44 Polynesians, as well as their 340 matched controls, in order to search for a genetic susceptibility at those polymorphic loci. All the subjects were tested for G1M (1, 2, 3, 17), G2M (23), G3M (5, 6, 10, 11, 13, 14, 15, 16, 21, 24, 28) and KM (1) by the classical hemagglutination method. The frequencies of GM haplotypes and KM alleles have been estimated by a maximum likelihood method. The results are in favour of no influence of the GM and KM loci. The prevalence of diabetes mellitus varies in the populations of New Caledonia: Polynesians are at much higher risk than Melanesians or Europeans. The GM haplotype distribution differs among ethnic groups; so they provide a useful marker to measure genetic admixture. The higher prevalence of diabetes observed among New Caledonians of European origin compared to the prevalence in Europe may be explained by genetic admixture with neighbouring Pacific populations, notably Polynesians (Asian haplotypes are present at a frequency of 9.4%). So, the genetic admixture should be measured in any genetic epidemiological study.

Adult↗
PubMed2000

No evidence for transmission disequilibrium between a new marker at the myelin basic protein locus and multiple sclerosis in French patients.

The myelin basic protein (MBP) gene is a candidate locus for susceptibility to multiple sclerosis. Several groups have tested a complex (TGGA)n repeat in the 5' region of this gene for association/linkage with multiple sclerosis, with divergent results. This region of tandem repetitive sequence has been subjected to complex rearrangements, and there is a possibility that alleles of the same size have different internal structures, which reduces the interest of this marker for linkage disequilibrium studies and may at least partly explain the conflicting results obtained so far. To overcome this problem, we isolated a new polymorphic (CA)n repeat within the Golli-MBP locus. The limited number of alleles identified makes this other marker suitable for transmission disequilibrium studies. We tested this marker for linkage with multiple sclerosis, using the transmission-disequilibrium test (TDT) on a sample of 196 nuclear families in which the genotypes of both parents could be unambiguously defined. We found no evidence of transmission disequilibrium between multiple sclerosis and any of the three alleles of this marker, even when the patients were subdivided according to their HLA-DRB1*1501 status. The present data thus provide no evidence for a contribution of the MBP gene to multiple sclerosis susceptibility in French patients.

Base Sequence↗
PubMed2000

Associated malformations in cases with oral clefts.

OBJECTIVE: Infants with oral clefts (OCs) often have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. METHOD: The prevalences at birth of associated malformations in infants with OCs were collected between 1979 and 1996 on all infants born in the area covered by the registry of congenital anomalies of Northeastern France in 238,942 consecutive births. RESULTS: Of the 460 cleft infants born during this period, 36.7% had associated malformations. Associated malformations were more frequent in infants who had cleft palate (46.7%) than in infants with cleft lip and palate (36.8%) or infants with isolated cleft lip (13.6%). Malformations in the central nervous system and in the skeletal system were the most common other anomalies, followed by malformations in the urogenital and cardiovascular systems. Weight, length, and head circumference of children with OCs and multiple associated malformations were lower than in controls, as was the weight of the placenta. Prenatal diagnosis was rarely done by fetal ultrasonographic examination in isolated clefts. However, even in multiple associated malformations, prenatal diagnosis by fetal ultrasonographic examination had a low sensitivity, 31.6%. CONCLUSION: The overall prevalence of malformations, which was one in more than three infants, emphasizes the need for a thorough investigation of infants with clefts. A routine screening for other malformations especially skeletal, central nervous system, and cardiac defects may need to be considered in infants with clefts, and genetic counseling seems warranted in most of these complicated cases.

Abnormalities, Multiple↗
PubMed1999

A genome-wide search identifies two susceptibility loci for experimental autoimmune encephalomyelitis on rat chromosomes 4 and 10.

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. The genetic loci that contribute to mononuclear cell infiltration of the central nervous system and clinical manifestations of EAE in the rat were investigated in the F2 progeny of the highly susceptible Lewis and resistant Brown Norway strains. The data confirmed that the Lewis allele of a MHC-linked gene is necessary, but not sufficient, to confer EAE susceptibility in the F2 progeny. Subsequent analyses were thus restricted to the subset of the F2 animals with EAE-predisposing MHC genotypes. A genome-wide scan approach was performed using 103 microsatellite markers covering 85% of the genome. Two non-MHC regions were identified, one near the centromere of chromosome 4 and the other on the long arm of chromosome 10, that significantly contributed to the disease. In addition, three regions on chromosomes 9, 13, and 17 were suggestive for linkage. Congenic mapping is now needed to reduce the support intervals encoding the loci of interest to sizes amenable to physical mapping and to eventually demonstrate the involvement of some of the candidate genes of immunologic importance localized in these regions.

Alleles↗
PubMed1999

Study of 290 cases of polyhydramnios and congenital malformations in a series of 225,669 consecutive births.

OBJECTIVES: To provide data on polyhydramnios associated with congenital anomalies in 225,669 consecutive pregnancies. MATERIAL AND METHODS: The information in this study came from births of known outcome recorded in our registry of congenital malformations. Routine ultrasonographic examination was performed. Polyhydramnios was diagnosed ultrasonographically. A case-control study allowed the examination of genetic and environmental causal factors of polyhydramnios associated with congenital malformations. RESULTS: The prevalence of this association was 1.28/1,000 (290 cases). Polyhydramnios associated with congenital malformations was diagnosed prenatally in 44.5% of the cases, 10.3% of the infants were stillborn. Forty-one percent of the cases had more than one malformation, 14.5% had a chromosomal aberration, and 20.0% had multiple malformations that do not constitute a syndrome. The more frequent malformations associated with polyhydramnios were cardiac, digestive, central nervous system, musculoskeletal, and urinary. There was increased parental consanguinity. The incidence of polyhydramnios and congenital anomalies among first-degree relatives was 4.1% and first-degree relatives had more malformations than controls (6.2 vs. 3.2%, p < 0.05). Threatened abortions and diabetes mellitus were significantly more frequent among mothers of children with congenital malformations associated with polyhydramnios than among controls. CONCLUSIONS: Our study demonstrated that careful fetal examination has to be performed when polyhydramnios is diagnosed as congenital malformations are often associated with polyhydramnios. We recommend the use of fetal chromosome analysis and careful ultrasonographic examination in every pregnancy complicated by polyhydramnios.

Journal Article↗
PubMed1999

Parental consanguinity as a cause for increased incidence of births defects in a study of 238,942 consecutive births.

The risk for birth defects in the offspring of first-cousin matings has been estimated to increase sharply compared to non consanguineous marriages. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies we tried to answer to this question. In the population studied in North-Eastern France a consanguineous mating was known in 1.21% of the cases with congenital anomalies, vs. 0.27% in controls, (p < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 89 malformed children, 51 were seen in first-cousins mating (10.3 times more frequent than in offspring of non consanguineous couples), 17 in second-cousins marriages and 18 in more distant relatives mating. Three were uncle-niece marriage. Excluding known mendelian conditions these numbers were 73, 36, 17 and 17 respectively and the corresponding relative risk were 3.68, 3.01, 3.41 and 4.89 respectively. Therefore there is a negative dose-response effect between level of inbreeding and risk of congenital malformations. Consanguineous mothers were more often pregnant than non consanguineous mothers (p < 0.01) and they had more stillbirths than non consanguineous mothers. These results show that consanguinity is still a factor of birth defects and they must be taken into account for genetic counseling of inbred marriages, in developed countries.

Congenital Abnormalities↗
PubMed1998

Study of 224 cases of oligohydramnios and congenital malformations in a series of 225,669 consecutive births.

OBJECTIVES: To provide data on oligohydramnios associated with congenital anomalies in 225,669 consecutive pregnancies. MATERIAL AND METHODS: The malformations in this study came from births of known outcome recorded in our registry of congenital malformations. Routine ultrasonographic examination was performed. Diagnosis of oligohydramnios was made ultrasonographically. For each case, a control was chosen. RESULTS: The prevalence of this association was 0.99 per thousand (224 cases). A case-control study allowed the examination of genetic and environmental factors for the origin of oligohydramnios associated with congenital malformations. Diagnosis of oligohydramnios associated with congenital malformations was made prenatally in 32.6% of the cases; 12.0% of the infants were stillborn. Fifty-nine percent of the cases had more than one malformation, 13.8% had a chromosomal aberration, and 27.6% had multiple malformations that do not constitute a syndrome. The more frequent malformations associated with oligohydramnios were urinary, musculoskeletal, digestive and cardiac. There was increased parental consanguinity. The frequency of oligohydramnios and congenital anomalies among first-degree relatives was 4.5% and first-degree relatives had more malformations than controls (8.0 vs. 3.1%, p < 0.05). Threatened abortions and diabetes mellitus were significantly more frequent among mothers of the children with congenital malformations associated with oligohydramnios than among the controls. CONCLUSIONS: Our study demonstrated that careful fetal examination has to be performed when oligohydramnios is diagnosed as congenital malformations are often associated with oligohydramnios. We recommend the use of fetal chromosome analysis and careful ultrasonographic examination in every pregnancy complicated by oligohydramnios.

Journal Article↗
PubMed1998

Study of Down syndrome in 238,942 consecutive births.

The genetics and the epidemiology of Down syndrome (DS) was studied in the area which is covered by our registry of congenital malformations. For each of the 398 new DS cases which were ascertained during the period 1979 to 1996 more than 50 factors were studied and compared to those from control infants. The prevalence of DS was 1.66 per 1000; 2.2% of the DS cases were stillbirths and 29.4% were induced abortions. Karyotypes were obtained in 391 cases of which all but 23 were 47,+21;9 were mosaics (2.3%), and 14 had translocations (3.6%). Interchromosomal effect was a question in 7 cases. The most common types of associated malformations were cardiac anomalies (46.2%) and intestinal atresias (6.0%). Seasonality or time/space clusters were not observed in spite of the Chernobyl nuclear accident. No paternal age effect was demonstrated; 5.3% of the mothers of DS had 2 previous spontaneous abortions (controls 3.7% p < 0.05). At birth, the DS infants measured and weighted less and their head circumference was lower than in control infants. Weight of placenta was also lower than in control infants. In this material there were 4.5% of consanguineous marriages (P < 0.01). The pregnancies of the DS children were more often complicated by threatened abortions than in the controls, 3.2% of the mothers of the DS children were diabetic controls (1.7%), although the difference was not statistically significant. For all other factors studied no statistically significant difference with respect to controls could be demonstrated.

Abnormalities, Multiple↗
PubMed1997

Heterogeneity in rates of recombination in the 6-Mb region telomeric to the human major histocompatibility complex.

Analysis of 784 informative meioses in the CEPH pedigrees revealed a total of 22 recombination events having occurred in the 6-Mb region between D6S265 (70 kb centromeric of HLA-A) and D6S276. These 22 breakpoints were localized with respect to anonymous polymorphic markers, leading to a detailed genetic map of the region telomeric to the human major histocompatibility complex. A nonrandom pattern of recombination was observed throughout this region: the low recombination rate of 0.19% within the 4-Mb interval centromeric to the HLA class I-like candidate gene for hemochromatosis indeed contrasts with the approximate 1% rate observed within the most telomeric two megabases. This reduced rate of recombination may be due to selective constraints depending on environmental factors related to immunity and iron status or to structural variations hampering proper meiotic pairing of homologous sequences. Population data from other human genome segments are now needed to determine whether linkage disequilibrium extending over 4 Mb is unique to this region.

Chromosome Mapping↗
PubMed1997

Conservation of ancestral haplotypes telomeric of HLA-A.

Genes that predispose to haemochromatosis are though to be located within the several megabases telomeric of HLA-A. Further recombinant mapping has been used previously to map susceptibility genes for diseases such as insulin-dependent diabetes mellitus, myasthenia gravis and cystic fibrosis, and should be useful in relation to haemochromatosis. However, this method requires the recognition of ancestral haplotypes within the susceptibility region. Using a panel of six microsatellite markers from this region (MOG A, MOG B, MOG C, D6S464, D6S306 and D6S105), we show that ancestral haplotypes extend telomeric of HLA-A, at least as far as D6S105. Nine of 14 haplotypes carrying HLA-B7 and HLA-A3 shared the same microsatellite alleles between HLA-A and at least D6S105. Similarly, nine of 10 haplotypes sharing HLA-B8 and HLA-A1 shared the same microsatellite alleles, although a different set to those with HLA-B7 and HLA-A3. Haplotypes representing historical recombination events were also identified. These two findings demonstrate that recombinant mapping may be applicable to the mapping of disease genes in this region.

B-Lymphocytes↗