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Biomedical subjects

M Kohler

Publications and source records attributed to M Kohler.

At least 19 recordsLinked to original sources

Prenatal diagnosis of congenital epulis. A case study.

Congenital granular epulis is a rare benign tumour situated on the alveolar ridge, which usually presents as a single tumour of variable size. Prenatal diagnosis of epulis has rarely been reported in medical literature. A possible complication is airway obstruction, which is essentially determined by the size of the tumour. Because of the potential risk of neonatal respiratory distress, prenatal diagnosis is valuable in the organization of a safe delivery. The case presented here is the prenatal diagnosis of a congenital epulis discovered in the 32nd week of pregnancy.

Adult↗

Interest of foetal nasal bone measurement at first trimester trisomy 21 screening.

OBJECTIVES: The purpose of this study is to assess the feasibility of foetal nasal bone (NB) measurement during the first trimester of pregnancy, and to examine the contribution of this measurement to the prenatal screening for Down syndrome following the definition of NB threshold using ROC curves in an unselected population. METHODS: This prospective study was carried out at our centre SIHCUS-CMCO (reference centre) from January 2002 to December 2004 on a total of 2,044 pregnant outpatients at gestational weeks 11-14. Only 1260 singleton foetuses were used for statistical analysis. In the 784 other patients, we were unable to obtain a correct image allowing a reproducible measurement. NB was measured during the same session as nuchal translucency (NT) measurement. Ten trained sonographers took part in the study. Correlation index was evaluated to shed light on a link between interest variables and NB. Screening values of NB measurement in T 21 were also calculated with NB measurement according to crown-rump length, and expressed as the best threshold of multiple of the median determined by ROC curve. Screening values of genetic ultrasound were then evaluated by adding NB measurement to maternal age and NT measurement. RESULTS: Two thousand and forty-four patients were included. We indexed 30 cases of T 21, 14 cases of Trisomy 18, 10 cases of Trisomy 13 and 25 cases of other karyotype abnormalities. Feasibility of measurement was 62% of all cases. We observed a significant relation between NB and NT (p = 0.001 ), as well as between NB and crown-rump-length (p < 0.0001 ). However, size of NB was not correlated to maternal ethnic group (p = 0.314). At 0.6 multiple of the median thresholds, screening values of NB measurement in T 21 were: sensibility 32%, false positive rate 10%, positive predictive value 13.6%, and negative predictive value 96.9%. The likelihood ratio for T 21 in case of NB < or = 0.6 multiple of the median was 4.4 (2.0-9.4). Screening values for maternal age and NT measurement were: sensitivity 88%, false positive rate 23%,positive predictive value 9.7%, and negative predictive value 99.6%. Inclusion of NB measurement increased sensitivity to 100%, positive predictive value to 13.6%, and negative predictive value to 100%, and decreased false positive rate to 5%. CONCLUSION: NB measurement seemed to be a great sonographic marker for T 21. However, its low feasibility made it inadequate for routine settings in first trimester T 21 screening in an unselected population. Statistical independence with NT thickness needed to be further evaluated.

Chromosome Aberrations↗

[Method and design of the Telephone Health Survey 2003].

Telephone surveys are increasingly being used in public health research, also in Germany. In 2003 the Robert Koch Institute completed the first nationwide telephone survey predominantly on conditions and prevalence of selected chronic diseases (GSTel03). Its findings are presented in this publication. The tasks of planning, implementation and realization of procedures used in telephone surveys differ in many aspects from other modes of data collection. This article deals with the most important methodological aspects that were implemented and used in the course of the GSTel03 to ensure a high level of data quality. These include sample design, questionnaire development and the process of data collection (including the recruitment and training of the staff). Finally steps of data preparation for analysis including weighting procedures are described and calculation of contact and cooperation rates are reported.

Data Interpretation, Statistical↗

Involvement of the retinohypothalamic tract in the photic-like effects of the serotonin agonist quipazine in the rat.

Light is the major synchronizer of the mammalian circadian pacemaker located in the suprachiasmatic nucleus. Photic information is perceived by the retina and conveyed to the suprachiasmatic nucleus either directly by the retinohypothalamic tract or indirectly by the intergeniculate leaflet and the geniculohypothalamic tract. In addition, serotonin has been shown to affect the suprachiasmatic nucleus by both direct and indirect serotonin projections from the raphe nuclei. Indeed, systemic as well as local administrations of the serotonin agonist quipazine in the region of the suprachiasmatic nucleus mimic the effects of light on the circadian system of rats, i.e. they induce phase-advances of the locomotor activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus during late subjective night. The aim of this study was to localize the site(s) of action mediating those effects. Phase shifts of the locomotor activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus after s.c. injection of quipazine (10 mg/kg) were assessed in Lewis rats, which had received either radio-frequency lesions of the intergeniculate leaflet or infusions of the serotonin neurotoxin 5,7-dihydroxytryptamine into the suprachiasmatic nucleus (25 microg) or bilateral enucleation. Lesions of intergeniculate leaflet and serotonin afferents to the suprachiasmatic nucleus did not reduce the photic-like effects of quipazine, whereas bilateral enucleation and the subsequent degeneration of the retinohypothalamic tract abolished both the phase-shifting and the FOS-inducing effects of quipazine. The results indicate that photic-like effects of quipazine are mediated via the retinohypothalamic tract.

Animals↗

Circulating cell-free fetal DNA in maternal serum appears to originate from cyto- and syncytio-trophoblastic cells. Case report.

Circulating cell-free fetal DNA in maternal serum offers an early and non-invasive method for prenatal diagnosis, but the origin of this DNA is still unknown. We report the absence of the SRY gene in maternal serum of a pregnant woman despite male genitalia at ultrasound. The karyotype was 45,X after direct trophoblast analysis and 45,X/46,Xidic(Yp) after culture and in all fetal tissues studied. Due to the absence of the SRY sequence in maternal blood and in the cytotrophoblast, we presume that free fetal DNA in this case originates from trophoblastic cells. As the case presented here is exceptional, it only has a minor impact on the accuracy of fetal sex determination by maternal serum analysis, but highlights the importance of and the necessity for the complementary ultrasonographic control.

DNA↗

The role of fetal nuchal translucency and ductus venosus Doppler at 11-14 weeks of gestation in the detection of major congenital heart defects.

OBJECTIVE: To determine whether, in a selected high-risk population, Doppler velocimetry of the ductus venosus can improve the predictive capacity of increased nuchal translucency in the detection of major congenital heart defects in chromosomally normal fetuses at 11-14 weeks of gestation. METHODS: Ductus venosus Doppler ultrasound blood velocity waveforms were obtained prospectively at 11-14 weeks of gestation in 1040 consecutive singleton pregnancies. Waveforms were classified either as normal in the presence of a positive A-wave, or as abnormal if the A-wave was absent or negative. All cases were screened for chromosomal defects by a combination of maternal age and fetal nuchal translucency thickness. In 484 cases karyotyping was performed. Those fetuses found to be chromosomally normal by prenatal cytogenetic analysis, and which had abnormally increased nuchal translucency and/or abnormal ductus venosus Doppler velocimetry, underwent fetal echocardiography at 14-16 weeks of gestation. Ultrasound examination was repeated at 22-24 weeks of gestation in all women. The sensitivity, specificity and positive and negative predictive values for the detection of major cardiac defects of increased nuchal translucency thickness alone, ductus venosus Doppler alone and increased nuchal translucency thickness in association with abnormal ductus venosus Doppler were determined. RESULTS: In 29 of 998 fetuses presumed to be chromosomally normal, reversed or absent flow during atrial contraction was associated with increased (> 95(th) centile for crown-rump length) nuchal translucency. Major cardiac defects were observed in 9 of these 29 fetuses. No other major cardiac abnormalities were found in chromosomally normal fetuses in spite of the presence of either increased nuchal translucency alone or abnormal ductus venosus velocimetry. A total of 25 cardiac malformations were observed in the population. Fifteen were associated with aneuploidy and 10 fetuses had a normal karyotype. Nine of the 10 had major cardiac anomalies and one had a ventricular septal defect. The nine cases with normal karyotype and major cardiac anomalies had both increased nuchal translucency and abnormal ductus venosus flow velocity waveforms. CONCLUSION: In chromosomally normal fetuses with increased nuchal translucency, assessment of ductus venosus blood flow velocimetry could improve the predictive capacity for an underlying major cardiac defect.

Adolescent↗

Binding of correolide to the K(v)1.3 potassium channel: characterization of the binding domain by site-directed mutagenesis.

Correolide is a novel immunosuppressant that inhibits the voltage-gated potassium channel K(v)1.3 [Felix et al. (1999) Biochemistry 38, 4922-4930]. [(3)H]Dihydrocorreolide (diTC) binds with high affinity to membranes expressing homotetrameric K(v)1.3 channels, and high affinity diTC binding can be conferred to the diTC-insensitive channel, K(v)3.2, after substitution of three nonconserved residues in S(5) and S(6) with the corresponding amino acids present in K(v)1.3 [Hanner et al. (1999) J. Biol. Chem. 274, 25237-25244]. Site-directed mutagenesis along S(5) and S(6) of K(v)1.3 was employed to identify those residues that contribute to high affinity binding of diTC. Binding of monoiodotyrosine-HgTX(1)A19Y/Y37F ([(125)I]HgTX(1)A19Y/Y37F) in the external vestibule of the channel was used to characterize each mutant for both tetrameric channel formation and levels of channel expression. Substitutions at Leu(346) and Leu(353) in S(5), and Ala(413), Val(417), Ala(421), Pro(423), and Val(424) in S(6), cause the most dramatic effect on diTC binding to K(v)1.3. Some of the critical residues in S(6) appear to be present in a region of the protein that alters its conformation during channel gating. Molecular modeling of the S(5)-S(6) region of K(v)1.3 using the X-ray coordinates of the KcsA channel, and other experimental constraints, yield a template that can be used to dock diTC in the channel. DiTC appears to bind in the water-filled cavity below the selectivity filter to a hydrophobic pocket contributed by the side chains of specific residues. High affinity binding is predicted to be determined by the complementary shape between the bowl-shape of the cavity and the shape of the ligand. The conformational change that occurs in this region of the protein during channel gating may explain the state-dependent interaction of diTC with K(v)1.3.

Alanine↗

Characterization of ageing products of ester-based synthetic lubricants by liquid chromatography with electrospray ionization mass spectrometry and by electrospray ionization (tandem) mass spectrometry.

Ageing products of a commercial jet engine oil based on pentaerythritol tetraesters which were formed upon operation in an aviation turbine were detected by electrospray ionization mass spectrometry (ESI-MS) and characterized by LC-ESI-MS. The fatty acid composition of these ageing products was investigated by ESI-MS-MS analysis. The ammonium adducts of the newly formed pentaerythritol tetraester degradation products were found to be suitable parent ions for further structure elucidation work. ESI-MS, LC-ESI-MS and ESI-MS-MS proved to be versatile tools to study the chemical composition (distribution of homologues) as well as the mechanism of ageing of ester based lubricants on a molecular level. Due to its high sensitivity, ESI-MS can also be used to characterize and identify trace levels of ester-based lubricants.

Chromatography, Liquid↗

Determination of Zn in high-purity GaAs with neutron activation analysis

Neutron activation analysis was used to analyse Zn concentrations in high-purity GaAs. A combination of chemical separation of the neutron-induced 65Zn from the GaAs-matrix with anion-exchange chromatography and ultra low-level gamma-ray spectrometry in an underground laboratory was applied. Zn concentration ranged from 2.1 to 51 ng g(-1), and detection limits from 0.018 to 0.059 ng g(-1) were obtained.

Journal Article↗

Recent developments in ultra low-level gamma-ray spectrometry at IRMM

IRMM performs ultra low-level gamma-ray spectrometry in the underground laboratory HADES, located at the SCK-CEN site in Mol, Belgium. Recently a third low-background coaxial HPGe detector was put into operation. The detector has 60% relative efficiency and better background characteristics than the two previous detectors: The shield comprises 14 cm of lead with 21OPb specific activity of 20 Bq kg(-1) and 14 cm of freshly produced electrolytic copper. The background count rate integrated from 40 to 2700 keV is 394 +/- 2 counts per day. Details of the background and the shield are presented together with applications to nuclear safeguards and material selection.

Journal Article↗

Simultaneous determination of Ra and Th nuclides, 238U and 227Ac in uranium mining waters by gamma-ray spectrometry

For the investigation of flooding processes in uranium mines, Ra and Th nuclides as well as 238U and 227Ac activities in waters were simultaneous analyzed by gamma-ray spectrometry. The activities of 227Ac and 228Th, not directly determinable by gamma-ray spectrometry, can be calculated from two consecutive measurements (approximately 25 d delay) of the progeny 227Th and 224Ra. For the short-lived radionuclides 234Th, 227Th, 223Ra and 224Ra a correction of the results to the sampling date is necessary.

Journal Article↗

Quality control of three methods for lung tumorigenesis studies.

Many variables influence experimental results obtained from laboratory animal studies. One of the variables is tissue sampling for the detection of lesions. The contribution of different levels of sampling to the variability in reported tumour rates was evaluated in a tumorigenesis study using 1872 CBA/J mice. The number of lung neoplasms was estimated by three methods and the results compared. These methods were: 1. counting the macroscopically visible nodules, 2. microscopical examination of macroscopically-detected nodules and one histological section of each lung lobe, cut at the level of the bronchi (common method) and 3. microscopical examination as in method number 2 and additional microscopic examination of step-sections (200 microm interval) of the remaining lung tissue beginning at the level of the bronchi. Analysis using only macroscopic examination (method 1) showed that 40% (747/1872) of the animals had single or multiple nodules (i.e. tumour suspicious areas) in the lungs. When combined with microscopic examination (method 2), primary lung tumours were diagnosed in only 586 animals (31%). Evaluation by gross examination alone therefore gave an apparent overestimation of lung tumours compared to microscopic evaluation of grossly visible nodules. This was found to be due to a significant number of mice having nodules formed by processes other than primary lung tumours (i.e. non-specific inflammation, alveolar histiocytosis, focal hyperplasia of the alveolar epithelium, lymphoma infiltration or tumour metastases). On the other hand, in the more thorough sectioning of the lungs (method 3), primary lung tumours were detected in 712/1872 animals (38%). Additionally, these three different methods influenced the results with regard to the tumour multiplicity in each tumour-bearing animal.

Adenoma↗

RITA/Registry of Industrial Toxicology Animal data: a comparative immunohistochemical study of 77 islet cell carcinomas in Sprague-Dawley and Wistar rats using antibodies against insulin, glucagon, somatostatin and gastrin.

UNLABELLED: The objective of this study was to investigate spontaneous islet cell carcinomas with particular reference to possible existing strain differences between Sprague Dawley (SD) and Wistar (W) rats in incidence and immunohistochemical staining pattern. Secondly the occurrence of somatostatin and/or gastrin-positive islet cell tumors should be tested. Islet cell adenocarcinomas (34 from SD, 43 from W-rats) were selected from the RITA-data base and company in-house data base out of an animal pool of 3915 (1681 SD, 2234 W-rats). They were untreated or sham-treated (vehicle) control animals from carcinogenicity studies and whole life-span experiments. Islet cell carcinomas occurred in a higher incidence in male rats (2.98% for SD, 3.23% for W) than in female rats (1.07% for SD, 0.63% for W). All specimens were immunohistologically stained with antibodies against insulin, glucagon, somatostatin and gastrin and, selected specimens with additional antibodies (pancreatic polypeptide, lipase, chymotrypsin, S100-protein, actin and cytokeratin). 94% (SD) and 93% (W), respectively, were insulin-positive and the mean staining intensity (on a scale ranging from 0-4) for insulin was 3.58 (SD) versus 3.37 (W). This high insulin staining incidence and intensity characterized most islet cell carcinomas as malignant insulinomas. 24% (SD) and 37% (W), respectively, were glucagon-positive. Except two tumors in W-rats with a focal strong glucagon expression, the mean staining intensity for glucagon was low (0.38 SD, 0.72 W). 38% (SD) and 44% (W), respectively, were somatostatin-positive, but except for five cases having a focal to multifocal, moderate to marked staining, only a few tumor cells were positive for somatostatin in the other cases and the mean staining intensity for somatostatin was low (0.50 SD, 0.84 W). 6% (SD) and 23% (W), respectively, were gastrin-positive, but only one case of a male Wistar rat exhibited a focal strong staining in parts of the tumor. The other cases showed only a few tumor cells which were positive for gastrin. The mean staining intensity for gastrin was low (0.06 SD, 0.35 W). In all tumors with marked glucagon, somatostatin or gastrin expression, the immunostaining for insulin was still predominating. Thus, insulin was the major hormone produced by most of the tumor cells. Five out of 77 tumors evaluated were immunohistologically negative with all applied antibodies. CONCLUSION: This study presents the first immunohistochemical survey on spontaneous islet cell carcinomas in SD and Wistar rats stained with antibodies against the endocrine pancreas hormones insulin, glucagon, somatostatin and gastrin. No major differences in incidence or immunohistochemical staining pattern between SD and W-rats could be detected. In contrast to SD rats, Wistar rats had multihormonal coexpression in 16.3%. The multihormonal appearance of the neoplasms is well comparable with the findings in other animal species and human insulinomas. Moreover, this is the first study in rats which reports five cases with a marked co-expression of somatostatin and one case with marked focal co-expression of gastrin in malignant islet cell adenocarcinomas.

Animals↗

Early fetal megacystis between 11 and 15 weeks of gestation.

OBJECTIVE: The purpose of this study was to evaluate the prognostic criteria of early fetal megacystis. DESIGN: A prospective, transvaginal ultrasound, cross-sectional study at 11-15 weeks of gestation at a tertiary referral fetal medicine unit. SUBJECTS AND METHODS: Sixteen pregnancies out of a total of 5240 were identified with early fetal megacystis. Fetal biometry, morphology, amniotic fluid, bladder size and volume were also evaluated. The karyotype was available in 15 cases. Vesicocentesis was performed in six fetuses and three had concomitant cystoscopies. RESULTS: In six fetuses, the megacystis was isolated. In the remaining ten, we detected associated hygroma (n = 5), nuchal translucency (n = 3), omphalocele (n = 1), mild pyelectasis (n = 1) and bilateral talipes (n = 1). In three cases the fetuses demonstrated renal hyperechogenicity with cysts, and in two cases oligohydramnios was found; four cases (25%) had chromosomal abnormalities; 47, XY + 13 (two cases), 47, XY + 18 and 47, XY + 21. Only one fetus from this study survived. In the remaining 13 cases, termination was proposed after counselling of the patients on the poor prognosis. The mean gestational age at termination was 15.5 +/- 2.4 weeks (range 12-20). Three fetal transabdominal cystoscopies did not allow us to view the valves; one urethral atresia was suspected, and confirmed postnatally. CONCLUSIONS: We found a high rate of associated malformations, especially intestinal malformations. The systematic evaluation of the intestinal enzymes in the amniotic fluid and urine samples might be an important aid in the diagnosis of multiple malformations, such as cloacal dysgenesis.

Abnormalities, Multiple↗

Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice.

A lifetime experiment using 4279 CBA/J mice was carried out to investigate whether the pre-conceptual exposure of sperm cells to X-ray radiation or urethane would result in an increased cancer risk in the untreated progeny, and/or increased susceptibility to cancer following exposure to a promoting agent. The study consisted of four main groups, namely a control group (saline), a urethane group (1 mg/g body wt) and two X-ray radiation groups (1 Gy, 2 Gy). At 1, 3 and 9 weeks after treatment, the males of these four parental groups were mated with untreated virgin females. The offspring of each parental group was divided into two subgroups: one received s.c. urethane (0.1 mg/g body wt once) as a promoter, the other saline, at the age of 6 weeks. All animals were evaluated for the occurrence of tumours. K-ras oncogene and p53 tumour suppressor gene mutations were investigated in frozen lung tumour samples. The female offspring of male parents exposed to X-rays 1 week before their mating showed a trend towards a higher tumour incidence of the haematopoietic system than the F1 controls. In addition, a higher percentage of bronchioloalveolar adenocarcinomas in male offspring born to irradiated paternals mated 1 week after X-ray treatment points to a plausible increased sensitivity of post-meiotic germ cell stages towards transgenerational carcinogenic effects. On the other hand, no increased tumour incidence and malignancy were observed in the offspring born to irradiated paternals mated 3 and 9 weeks after X-ray treatment. Paternal urethane treatment 1, 3 and 9 weeks prior to conception did not result in significantly altered incidence or malignancy of tumours of the lung, liver and haematopoietic tissue in the offspring. K-ras mutations increased during tumour progression from bronchioloalveolar hyperplasia to adenoma. Codon 61 K-ras mutations were more frequent in lung tumours of urethane-promoted progeny from irradiated parents than from control parents. P53 mutations were absent from these lung alterations.

Adenocarcinoma↗

Serotonin agonist quipazine induces photic-like phase shifts of the circadian activity rhythm and c-Fos expression in the rat suprachiasmatic nucleus.

Nonphotic stimuli can reset and entrain circadian activity rhythms in hamsters and mice, and serotonin is thought to be involved in the phase-resetting effects of these stimuli. In the present study, the authors examined the effect of the serotonin agonist quipazine on circadian activity rhythms in three inbred strains of rats (ACI, BH, and LEW). Furthermore, they investigated the effect of quipazine on the expression of c-Fos in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Quipazine reduced the amount of running wheel activity for 3 h after treatment, however, no long-term changes in tau and in the activity level were observed. More important, quipazine induced significant phase advances of the activity rhythm and c-Fos production in the SCN at the end of the subjective night (Circadian Time [CT] 22), whereas neither phase shifts nor c-Fos induction were observed during the subjective day. Quipazine injections also resulted in moderate phase delays at the beginning of the subjective night (CT 14). A similar phase-response characteristic typically can be observed for photic stimuli. By contrast, nonphotic stimuli normally produce phase advances during the subjective day. The present results suggest species differences between the hamster and the rat with respect to the serotonergic action on circadian timekeeping and indicate that serotonergic pathways play a role in the transmission of photic information to the SCN of rats.

Animals↗

[Congenital generalized dropsy and intrapericardial fetal teratoma. Report of a case of prenatal diagnosis].

Intrapericardial teratomas are rare tumors usually occurring in early infancy. Such a case was diagnosed in a 20 week old fetus, with a lethal outcome. About fifteen cases of intrapericardial teratoma have been reported in the fetal period. They are usually symptomatic, with a more or less severe pericardial effusion, sometimes complicated by cardiac compression and/or hydrops fetalis. Prognosis of the prenatally diagnosed pericardial teratomas is more related to the occurrence of hydrops fetalis than to the behavior of the tumor itself. The main interest of sonographic ante-natal diagnosis consists of the possible improvement of hemodynamic consequences through in utero pericardiocentesis. Macroscopic and microscopic features of this cardiac tumor are similar to those of extrapericardial teratomas. Most tumors discovered in fetal period are mature and histologically benign lesions. Only one case showed immature components. The coexistence of a malignant component (germ cell or non germ cell tumor) has been described in the postnatal and adulthood.

Adult↗