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Biomedical subjects

H Müntefering

Publications and source records attributed to H Müntefering.

At least 19 recordsLinked to original sources
PubMed2004

[Placenta in gestational hypertension].

At an incidence of 3.2-4% world-wide, pregnancy-induced hypertension (PIH) is the most common disease of pregnancy. Since this holds a risk, not only for the mother, but also for the child, the placenta should undergo pathological-anatomical examination in every case. Pathomorphological findings can be described in the feto-maternal border zone as well as in the fetal placenta. These are not, however, specific, nor do they offer diagnostic proof. Pathomorphological findings in the feto-maternal border zone: defective invasion of the extravillous cytotrophoblast, hyperplastic arterio-/arteriolopathy, acute atherosclerosis, and fibrinoid necrosis of endothelium. Disorders of the fetal part of placenta: infarctions/fibrin deposits, obliterative angiopathy, stromal fibrosis/fibrinoid degeneration, syncytiotrophoblastic nodes (Tenney-Parker-phenomenon), and disturbances of maturation of the villi. There is a general lack of correlation between the seriousness of the disease and the morphology. The only exception in this respect are the findings in the vessels both of the placental bed and of the chronic villi. These show a high correlation with doppler sonographic findings.

Abruptio Placentae↗
PubMed2004

[Congenital disorders of the colonic innervation. A diagnostic guide].

Hirschsprung's disease (HD, aganglionosis) is the most important form of congenital disturbance of intestinal innervation, requiring surgical intervention. Furthermore, hypoganglionosis of the transitional zone forms the most significant factor in morbidity. Pre-operative definition of the length of neuronally disturbed segment is still a diagnostic challenge for both clinical physician and pathologist. Enzyme histochemical studies form the method of choice, but certain limitations in their use must be observed. Other dysganglionoses, particularly the so-called "Intestinal Neuronal Dysplasia" (IND) cannot-because of an excessive overlapping with age-correlated normal values-unequivocally be defined as an entity on its own. The only exception to this, is the ganglionic neuromatosis, which arises as part of a genetic illness.

Diagnosis, Differential↗
PubMed2001

Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous abortions.

Comparative genomic hybridisation (CGH) represents an alternative molecular-cytogenetic technique capable of detecting chromosomal imbalances by reverse fluorescence in situ hybridisation. As the technique uses genomic DNA for assessment it does not rely on metaphase chromosomes in the test material and thus circumvents technical problems associated with tissue culturing. In the present study, we applied CGH to identify chromosome anomalies in 60 spontaneous abortions of the first trimester, that had failed to grow in culture. In 57 out of 60 cases CGH analyses were successful. The overall aneuploidy rate detected was 72%. Trisomy was the predominant chromosome anomaly accounting for 68.0% of abnormal abortions, followed by triploidy (17.1%) and monosomy X (9.8%). An unbalanced structural rearrangement was found in one (2.4%) abortion. Most frequently involved in trisomies were chromosomes 16 (32.1%), 7 and 22 (10.7% each), 4, 13, 15, and 21 (7.2 % each). Three triploid cases and one complete mole were detected by microsatellite analysis as supplementary method. CGH data on culture failures were compared with data derived from 4693 successfully karyotyped first trimester spontaneous abortions, resulting in a chromosome aberration rate of 64.8%. The distribution of the different chromosome anomalies was similar with the exception of a higher rate of trisomies 7 and of XYY-triploidies in the culture failures. Based on our data we suggest that the genetic contribution to pregnancy loss is still underestimated. Investigating abortion tissues hitherto unassessed by conventional methods, we suggest that the contribution of chromosome aberrations to first trimester pregnancy loss is nearly 70%.

Abortion, Spontaneous↗
PubMed2001

[Single umbilical artery. Effect on fetal growth and doppler flow velocity wave form].

OBJECTIVE: Fetuses with single umbilical arteries (SUA) are often small for gestational age (SGA). We tried to clarify the following questions: 1. In which range of the normal reference chart for 2 umbilical arteries are the S/D-ratios of SUA located? 2. Is it possible to correctly predict the fetuses at risk for asphyxia or fetal death using these reference charts in SNA fetuses? 3. How do placental weight and histological findings in the fetoplacental vessel influence flow patterns in SUAs? 4. How does the vessel diameter of SUAs influence fetal growth? PATIENTS AND METHODS: 25 fetuses with SUA were examined by means of ultrasound and Doppler ultrasound 1 to 9 times with measurements of arterial diameter and S/D-ratio. These data were compared with results of normal umbilical cords (data from the literature) and correlated with fetal outcome and histological placental findings. RESULTS: Out of 94 individual measurements the S/D-ratio was found to be below the 10th percentile in 28 cases (30%), between the 10th and 50th percentile in 31 cases (33%), between 50 and 90th 20 cases (21%), and above the 90th percentile of the reference chart in 15 cases (16%). 14 fetuses were SGA, 2 presented an intrauterine death, 2 were born with chromosomal aberrations and 3 with malformations. 5/6 fetuses with caesarean section for asphyxia or fetal demise were correctly detected to show an elevated S/D-ratio, 1 case of intrauterine death was not. 16/19 placentas were found to be of low weight, in 14 we found villous malmaturation. 18/22 examined SNAs had an elevated diameter above the +2s range of the reference chart for normal arteries. The ratio of the diameters of the umbilical vein and artery was above 2 in 12/14 SGA fetuses, indicating that the SNA's diameter was less than 50% of that of the veins in these cases. CONCLUSION: Widening of the SNA lumen leads to a reduction of the S/D-ratio. An SNA diameter of less than 50% of that of the vein results in intrauterine growth retardation. Elevated S/D-ratio correctly identifies SNA-fetuses at risk.

Asphyxia Neonatorum↗
PubMed2001

Immunohistochemical expression analysis of inhibin-alpha and -beta subunits in partial and complete moles, trophoblastic tumors, and endometrial decidua.

The expression of inhibin-alpha subunit has been described in normal placentas, hydatidiform moles, and trophoblastic tumors. We performed a double immunohistochemical expression analysis of inhibin-alpha and inhibin-beta subunits in a cytogenetically well characterized series of 21 complete and 22 partial hydatidiform moles, 2 placental site trophoblastic tumors, and one choriocarcinoma. Syncytiotrophoblastic cells were consistently inhibin-alpha and inhibin-beta positive in all hydatidiform moles and in the one choriocarcinoma. Cytotrophoblast was negative for both subunits in all trophoblastic lesions studied. While villous intermediate trophoblastic cells were consistently inhibin-alpha negative in all hydatidiform moles, focal inhibin-beta immunoreactivity was detected in villous intermediate trophoblast in approximately one third of complete and partial hydatidiform moles. Decidual stromal cells in 40 hydatidiform moles were inhibin-alpha and inhibin-beta positive in approximately one third of cases. Both placental site trophoblastic tumors were inhibin-alpha positive but inhibin-beta negative. Our findings indicate that inhibin-alpha and -beta subunits are consistently coexpressed in syncytiotrophoblast in complete and partial moles. Immunohistochemical detection of inhibin subunits may be useful in the differential diagnosis of trophoblastic lesions.

Choriocarcinoma↗
PubMed2001

Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. METHODS: We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. RESULTS: Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. CONCLUSIONS: The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND.

Alleles↗
PubMed2000

Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p.

We report on two sibs, both males, one born at 37 the other at 24 weeks of gestation, both with a syndrome similar to that seen in three sets of sibs by Gillessen-Kaesbach et al. [1993: Am J Med Genet 45:511-518]. Both propositi had polycystic kidneys and hepatic fibrosis indistinguishable from that seen in autosomal recessive polycystic kidney disease (ARPKD), and skeletal and facial anomalies. Skeletal abnormalities included "butterfly" vertebrae, square shape of pelvis, and brachymelia. The facial anomalies included hypertelorism, epicanthic folds, and anteverted nares. Additional external findings were apparently low-set ears and a short neck. Histopathological examination of the kidneys showed radial orientation and cystic dilatation of the cortical and medullar tubules. The liver showed "congenital hepatic fibrosis." The hepatic findings in the second infant were less severe. Renal abnormalities were limited to focal tubular cystic changes. Linkage analysis with polymorphic markers of the region 6p21.1-p12, flanking the gene locus of ARPKD, showed different haplotypes in the sibs, thus excluding the ARPKD gene locus in this family and indicating genetic heterogeneity.

Abortion, Induced↗
PubMed2000

Renal tubular dysgenesis (RTD) - an important cause of the oligohydramnion-sequence. Report of 3 cases and review of the literature.

Renal tubular dysgenesis (RTD) is a disorder characterized by neonatal renal failure and regular gross renal architecture, although the histological features of immature and shortened proximal tubules lead to neonatal death. The pathogenesis of this condition includes a congenital familial condition, a twin-twin transfusion syndrome, and an angiotensin-converting enzyme inhibitor intake by the mother. The clinical picture shows an association with oligohydramnia, pulmonary hypoplasia, and skull ossification defects. In the present paper, we report the occurrence of RTD in three infants of a consanguinous couple and compared our data with those of the literature. Our data confirm that late second trimester demonstration of oligohydramnion, with structurally normal kidneys and with or without skull ossification defects, allows the diagnosis of renal tubular dysgenesis, which, however, has to be confirmed by histological and immunohistological examinations of the kidney.

Adult↗
PubMed1999

Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome.

BACKGROUND: Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS: The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS: 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's kappa statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS: The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease (kappa = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS: In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease.

Adolescent↗
PubMed1993

Pathogenesis of HSV-1/2 induced vaginitis/vulvitis of the mouse: dependence of lesions on genetic properties of the virus and analysis of pathohistology.

A scoring system for herpes simplex virus (HSV) induced vaginitis/vulvitis in Balb/c mice was delineated from vaginal infections. Four degrees of vaginitis/vulvitis could be distinguished after infection with suitable strains of HSV despite nearly identical replication rates. The time course of replication, inflammation and pathohistology was compared further. Grade 0 was defined by lack of symptoms despite presence of strong replication, which was detectable at days 3-6. Focal necrotic lesions of the epithelial layer were present containing HSV-specific antigens. DNA could be detected by hybridization only in the outer zone of these areas. At day 6 these zones began to be re-epithelialized. In the vaginal lumen abundant detached epithelial cells and granulocytes were already present by day 2. Grade 1 was macroscopically characterized by a slight inflammation commencing on days 5-6. Replication and antigens in the epithelium were found on days 2-6. HSV-antigens were only detected above the basal membrane, and some infiltration with granulocytes and lymphocytes was observed below the basal membrane at day 4. Grade 2 showed strong redness and inflammation as well as hyperemia. Cellular infiltrates were present in the large antigen containing epithelial lesions and below the basal membrane. From day 4 on, neurons were HSV-antigen and DNA positive and macrophages in the stroma contained antigen. The vulva was also shown to be involved. Grade 3 exhibited prolonged severe hyperemia, and destruction of the epithelium and the stroma with necrosis and infiltration, especially of the vulva. This grading system was shown to depend on certain unknown genetic properties of HSV-strains. Neither thymidine-kinase activity, replication in macrophages, fusion activity of strains nor presence or absence of the Hpa I P-fragment were shown to be of importance for severity of vaginitis/vulvitis. Vaginitis/vulvitis was shown to be an all or none response to HSV independent of the rate of replication. The set of virus genes responsible for neuroinvasiveness after vaginal or i.p. inoculation was found to be different. The time course of replication (mainly days 3-6) and inflammation (days 5-10) indicates that inflammation seems to be a secondary immunological phenomenon induced later by the replication phase of HSV. Our system could be useful for separately testing drugs with antiviral and anti-inflammatory properties.

Animals↗
PubMed1993

Cell types infected in human cytomegalovirus placentitis identified by immunohistochemical double staining.

Chronic villitis is almost always present in intrauterine infection with human cytomegalovirus (HCMV). The inflammatory response to this virus has been described in detail. However, little is known about the types of placental cells that may be infected by HCMV and six cases of HCMV placentitis were thus investigated to identify the vulnerable cell types. Immunohistochemical double staining analyses were performed using antibodies to HCMV immediate early antigens and to specific cellular marker proteins. Fixed connective tissue cells could be demonstrated to be the predominantly infected cell type in each placental tissue. Endothelial cells and macrophages were also found to be infected in all six cases, whereas evidence of trophoblast infection was obtained in four cases. It is concluded that release of infectious virus by connective tissue cells, macrophages and endothelial cells may play a critical role in transplacental transmission of HCMV. The findings further suggest that the cytopathic effect of HCMV infection on these cells might be involved in the pathogenesis of intrauterine HCMV disease.

Antigens, Viral↗
PubMed1992

[Doppler sonography of the umbilical artery for evaluating the fetoplacental vascular tree: a prospective histologic comparison].

We compared the clinical data, Doppler sonographic results and histological placental findings of 252 patients prospectively. A normal flow velocity wave form may be related either to a normal placenta villous and vessel architecture or to an at least focal leason with compensatory angiosis and/or high placental weight, whereas in cases with missing compensation phenomenon the end-diastolic blood flow velocities in the umbilical arteries are reduced.

Asphyxia Neonatorum↗
PubMed1992

[Placental morphometry in diastolic zero and negative flow of the umbilical arteries].

Macromorphometric and histometric placental data, in cases with enddiastolic zero flow or reverse flow (dZRF), reveal a lower placental weight and smaller attachment area as well as bigger terminal villi with a reduced amount of epithelial plates with comparable vascularisation. In cases with reverse flow, all parameters were worse, either compared to the controls or to the zero flow cases. With advancing duration of clinical observation, we find a maturation of the terminal villi, with the cross-sectional areas getting smaller, diffusion distances becoming shorter and vessels bigger. This proves the dependence of foetal outcome by dZRF on the compensatory capacity of the terminal villi. The planimetric area in the forward flow channel depends on the foetal intravillous blood volume.

Blood Flow Velocity↗
PubMed1992

[Histologic placenta findings in diastolic zero or negative flow of the umbilical arteries: a prospective study with reference to the duration of clinical observation].

37 cases with enddiastolic zero flow or reverse flow (dZRF) in the umbilical arteries were compared with 37 gestational age-matched controls. In dZRF the placenta is significantly smaller (weight and basal area) throughout the entire gestational age. Vascularisation of the villous tree is often reduced in cases with dZRF, but the findings are not uniform. However, there is a direct interdependence of the histologic findings of villous maturation, terminal villus deficiency, reduced vascularisation and endangiopathia obliterans from the duration of clinical observation. The longer the control period was, the higher was the amount of accelerated villous maturation, angiosis of terminal villous vessels, less endangiopathia obliterans, with simultaneously improved foetal outcome. We conclude from these data, that the main placental lesion, which may cause dZRF, is located in the central villous tree and vascular tree, which is possibly related to the smallness of the placenta, whereas the changes in the terminal villi may exercise compensatory functions and may influence foetal outcome.

Blood Flow Velocity↗
PubMed1991

[Accumulation of two different hydroxyethyl starch preparations in the placenta after hemodilution in patients with fetal intrauterine growth retardation or pregnancy hypertension].

In a prospective clinical study the safety of two hydroxyethylstarch preparations (HES steril 10%, Fresenius AG, Oberursel = HES-A; Haemufusin, Kabi-Pfrimmer, Erlangen = HES-B) were assessed. In 60 patients with fetal growth retardation and/or gestational hypertension, hematocrit, aPTT, factor VIIIR: Ag, fibrinogen, uric acid, cord blood hemoglobin, hematocrit, pH-value and the fetal/maternal hydroxyethylstarch concentration before and after eight (HES-B) or nine (HES-A) days of treatment were monitored. 500 ml HES-A (n = 36) or HES-B (n = 24) together with the same volume electrolyte solution, were infused daily. Both substances lowered significantly the maternal and fetal hematocrit. Histopathological changes of placenta (trophoblast cells and stroma) taking place after the infusion of HES-A or HES-B were depicted by light microscopy. Administration of HES-A or HES-B was associated with lower values of factor VIIIR: Ag and a prolongation of aPTT, but only HES-B demonstrated a significant effect (31% vs. 12%, p less than 0.01). We observed in 4 (16.7%) cases severe uterine bleeding complications and one woman (4.2%) with abruptio placentae in the group HES-B. Light microscopy shows vacuoled trophoblast and stroma cells after HES infusions. The marked vacuolisation of the placenta after HES-B is due to differences in the physicochemical characteristics of HES-A and HES-B. For this reason, we prefer to administer HES-A in the dilution treatment of patients with placental insufficiency.

Adolescent↗
PubMed1990

[Does vascularization of the fetal placenta modify end-diastolic blood flow velocity in umbilical arteries? A histometric contribution to the validation of Doppler ultrasound].

The foetal intravillous blood volume was approximately determined in 90 cases, using placental histiometry post partum. This was compared with the Doppler sonographic flow patterns in the umbilical arteries determined during the last week ante partum. A direct dependence was seen: The larger the peripheral vascular tree of the placenta fetalis, the lower the resistance against the blood flow in the umbilical artery, i.e. the higher the enddiastolic blood flow velocities and vice versa. There is a highly significant correlation between the foetal intravillous blood volume and the foetal risks of Caesarean section performed, because of intrauterine asphyxia, growth retardation or reduced foetal outcome.

Asphyxia Neonatorum↗