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W Meier-Ruge

Publications and source records attributed to W Meier-Ruge.

At least 19 recordsLinked to original sources
PubMed2000

Clinical long-term follow-up results in intestinal neuronal dysplasia (IND).

Commonly available information on intestinal neuronal dysplasia (IND) is sparse. Especially well documented long-term courses are lacking. The aim of this study was to correlate defecation as a clinical parameter of the long-term course in malformations of the enteric nervous system with the morphological diagnosis. 57 children with intestinal neuronal dysplasia (IND) or aganglionosis with cranial intestinal dysganglionosis (agIND), diagnosed between 1983 and 1992, were analysed including histomorphological classification, collection of clinical data and evaluation of the defecation mode by questionnaire as a parameter of the long-term course. Of 29 dysganglionic (IND) patients, 9/29 cases (31 %) had been treated conservatively, 18/29 cases surgically (62.1%), in two children (6.9%) no therapy had been necessary. All 28 patients with Hirschsprung's disease and cranial IND (agIND) underwent resection. 46 of the children could be followed up 3.64 years after the end of the main therapeutic period and with a mean age of 6.7 years at the time of follow-up; 43.5% of the analysed children still showed severe constipation. 23.9% only were really cured; 15.2% had normal defecation still using conservative treatment and 17.4% had diarrhea. No significant difference was found between both groups, IND and agIND, and the results were independent of treatment modality. The results were much worse than in idiopathic constipation as reported in the literature and even worse in comparison to unselected Hirschsprung collectives. It has to be concluded that in IND with chronic constipation intensive long-term care is necessary and it is crucial that treatment algorithms should be outlined urgently together by pediatric gastroenterologists and pediatric surgeons. AgIND seems to need more extended resection following an exact histomorphological mapping by biopsies taken during enterostomy procedure.

Child↗
PubMed1999

[Intestinal neuronal dysplasia in adults as a cause of chronic constipation: morphometric characterization of colon innervation].

Intestinal neuronal dysplasia (IND) was initially described as a developmental abnormality of the submucous plexus in children. In recent years this abnormality has also been observed in adults with chronic constipation. The aim of this study was a morphometric characterization of this disease. The investigation was performed with 10 adults with IND, compared with 10 healthy control probands. The best diagnostic indicator of IND proved to be the detection of 6-10 giant ganglia with more than 7 nerve cells in 15 biopsy sections. IND is an interesting cause of chronic constipation which can be histologically verified.

Adult↗
PubMed1999

Intestinal transit time in children with intestinal neuronal malformations mimicking Hirschsprung's disease.

A total of 106 consecutive children with intestinal neuronal malformations were included in a prospective study. The intestinal transit time was assessed using a modification of Hinton's method. The results of transit time studies, the associated specific histochemical findings, therapeutic procedures, and the clinical course on follow-up assessments over a mean period of 2.4 years were analysed. The intestinal transit time was prolonged in all 53 patients with aganglionosis and in 37 (69.8%) out of 53 children with other intestinal malformations. Eight out of 16 children with IND type B had an abnormal transit time, 1 underwent anterior resection, and 2 had a temporary colostomy. In 7 out of 8 children with hypoganglionosis and 9 out of 10 children with a reduced parasympathetic tone the transit time was prolonged. A resection was performed in 7 and 2 of these children respectively. Both patients with heterotopia of the myenteric plexus had a prolonged bowel transit and parts of the large bowel had to be resected. Only 11 out of 17 children with heterotopia of the submucous plexus, dysganglionosis, or immature ganglia had a prolonged transit time, 2 underwent sphincteromyotomy. At follow-up, all patients with malformations other than aganglionosis stated that symptoms had improved and they were willing to tolerate their complaints. However, 25 reported on persistent constipation, 6 on overflow encopresis. All children who required surgery had a prolonged intestinal transit time, but also 21 (56.8%) of 37 children who were successfully treated without surgery. None of the 16 children with normal transit had to be operated. It is concluded that specific histochemical findings do not always correlate with delayed intestinal transport. The determination of the intestinal transit time represents an important tool to identify the clinical relevance of histochemical findings in the individual patient.

Child, Preschool↗
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↗
PubMed1998

Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging.

The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.

Aging↗
PubMed1997

Clinical impact of intestinal neuronal malformations: a prospective study in 141 patients.

A prospective study of 141 consecutive patients with intestinal neuronal malformations is presented. The single malformation of the autonomic nervous system that always required surgical intervention was aganglionosis. Giant ganglia, reduced parasympathetic tone, immature ganglia, and hypogenetic or heterotopic nerve cells were seen in all forms of malformations. However, the incidence in specific malformations was variable. Multiple giant ganglia were identified in all patients with intestinal neuronal dysplasia (IND) type B, but also in various other malformations. Heterotopic nerve cells in the myenteric plexus were seen in the proximal segment of 15 of 74 patients (20.3%) with aganglionosis and 5 of 9 patients (55.6%) with hypoganglionosis. A significant impact on symptoms was found for IND type B: 34 (45.9%) of 74 children with aganglionosis had associated IND type B, and these children more frequently developed ileus (P < 0.001) and more often needed a second resection (P < 0.05) compared to those with isolated aganglionosis. This indicates an additive effect of both malformations, and therefore, in these patients an extended resection should be carried out. Twelve of 67 patients (17.9%) without aganglionosis needed resection for untreatable constipation. This included 7 of 9 children with hypoganglionosis, both patients with heterotopia of the myenteric plexus, 1 of 20 with isolated IND type B, and 2 of 12 with reduced parasympathetic tone. None of the patients with immaturity, heterotopia of the submucous plexus, or mild dysganglionosis required surgery. Six children (8.9%) without aganglionosis underwent sphincteromyotomy and 2 with IND type B had a temporary colostomy. At follow-up (mean 2.4 +/- 1.4 years), the outcome in patients with resected aganglionosis was better than in patients who had resections for other malformations; 49 (69%) of 71 patients with aganglionosis were asymptomatic compared to 4 (33.3%) of 12 with other malformations (P < 0.05). It is concluded that some intestinal malformations have a relevant clinical impact. However, the severity of symptoms in the individual patient may not be explained by specific histochemical findings from a limited number of mucosal biopsies. The pathognomonic histochemical criteria of isolated IND type B - immaturity, reduced parasympathetic tone, heterotopia of the submucous plexus, and mild dysganglionosis - rarely require surgical therapy and should be treated conservatively.

Child↗
PubMed1997

[Prospective study of the transit time in intestinal neuronal abnormalities].

In a prospective study 106 children with intestinal neuronal malformations underwent intestinal transit-time studies. In only 50% of the children with intestinal neuronal dysplasia type B or immature ganglia was the transit time prolonged. On the contrary, hypoganglionosis and heterotopia of the submucous plexus led to severe transport disorders with subsequent bowel resection.

Adolescent↗
PubMed1996

Age-dependent decrease in the activity of succinic dehydrogenase in rat CA1 pyramidal cells: a quantitative cytochemical study.

A computer-assisted morphometric study has been carried out on the ultrastructure of perikaryal CA1 pyramidal cell mitochondria positive to the copper ferricyanide cytochemical reaction for succinic dehydrogenase (SDH) in rats of 3, 12 and 23 months of age. The cytoplasmic volume fraction occupied by the positive mitochondria (Volume density: Vv), the number of organelles/micron 3 of CA1 pyramidal cell cytoplasm (Numerical density: Nv) and the average mitochondrial volume (V) were automatically calculated by means of computer-assisted morphometry. Vv was significantly decreased in 23-month-old animals versus the other age groups. Nv was unchanged between 3 and 12 months of age, but was decreased to a significant extent in old animals. V did not undergo significant changes in the three age groups taken into account. In the old animals the percent of organelles smaller than 0.16 micron 3 is above 20%, while in the young and adult groups the same size of mitochondria accounts for 7 and 3%, respectively. Thus, a reduction in the number of medium sized organelles appears to be responsible for the decrease in Vv due to age. Since SDH activity is known to support maximum rates of respiration, quantitative estimation of the active mitochondria provides information on the metabolic competence of the cells investigated when energy demand is high. In this context, our present findings document that a significant impairment in the efficiency to match actual energy provisions occurs in old CA1 pyramidal cells.

Age Factors↗
PubMed1996

Innervation patterns of the rectal pouch and fistula in anorectal malformations: a preliminary report.

The innervation patterns of the rectal pouch and fistula of 52 children with anorectal malformations were investigated. Posterior sagittal anorectoplasty was used for intermediate and high anomalies; for the latter it was combined with an abdominal approach. Perineoproctoplasty was performed for low anomalies. The specimens were investigated by acetylcholinesterase staining, lactate dehydrogenase, and succinyldehydrogenase reaction. They consisted of fistula material only in 23 patients and of parts of the rectal pouch in 29. Fourty-four patients (84.6%) had follow-up, and information of bowel movements and continence was obtained after a mean of 3.3 years. Abnormal innervation patterns were found in 96% of the specimens. All fistulas were found to be aganglionic, including the adjacent part of the rectum involving the internal sphincter equivalent. Classical aganglionosis was found in 31% of the rectal pouch specimens, hypoganglionosis in 38%, neuronal intestinal dysplasia (NID) type B in 14%, and dysganglionosis in 10%. All patients with severe constipation or soiling at the time of follow-up had some histopathological correlation. Of the 25 patients for whom the specimens had consisted of rectal pouch material, nine (31%) had severe constipation. All four patients with a low-type malformation who had follow-up and pathological innervation patterns in the rectal pouch suffered from severe constipation; this was true of only five of the 19 children with intermediate or high malformations (P < .05). However, numerous pathological innervation patterns had been identified in patients who had normal bowel function at the time of follow-up. It is concluded that partial denervation of the rectum may not be the only cause in the pathogenesis of constipation after posterior sagittal anorectoplasty and perineoproctoplasty. The high frequency of neuronal intestinal malformations in the rectal pouch may be related to the higher frequency of bowel disturbances in patients with low malformations, in whom the resection was less radical. However, the clinical course is not necessarily related to specific histopathological findings. In the authors' opinion, the recommendation to use the distal rectal pouch and parts of the fistula in the reconstruction of anorectal malformations should be reconsidered.

Anus, Imperforate↗
PubMed1996

Synaptic structural dynamics and aging.

Synaptic junctional areas are not immutable structures, on the contrary, they are remodelled throughout the individual's lifespan as a consequence of environmental stimulations. This adaptive capacity of the synapses is discussed from a morphological standpoint with reference to aging. In old subjects, the number of contacts and the total surface area of synaptic appositions per unit volume of tissue decrease significantly, while the average synaptic size increases at a different extent according to the CNS area taken into account. This increase in synaptic average area is due to a higher percent of a subpopulation of enlarged contacts supposed to represent either the degenerating junctional zones or a compensatory phenomenon counteracting the synaptic reduction in number. Recent studies on perforated synapses support that the enlarged junctions are possible intermediates in synaptic physiological restructuring, thus the higher percentage of this type of contacts in the old CNS may witness unaccomplished synaptic turnover cycles. Taking into account the high metabolic rate of nerve cells, an age-related impairment in energy provision at synaptic terminal regions may constitute an early and subtle alteration affecting synaptic dynamic morphology in aging.

Aging↗
PubMed1996

Morphologic changes in cerebellar mitochondria during aging.

OBJECTIVE: To seek age-dependent morphofunctional changes in mitochondrial metabolic competence in the rat cerebellum. STUDY DESIGN: Three-, 12- and 24-month-old female Wistar rats were used for the present study. Each group consisted of five animals. The cytoplasmic fraction occupied by mitochondria (volume density, Vu), number of organelles per cubic micrometer (numerical density, Nu) and mitochondrial average volume (V) were measured in Purkinje cell perikaryal organelles histochemically stained to reveal succinic dehydrogenase activity in the three groups analyzed. RESULTS: Vu did not show significant differences due to age. Nu was constant between 3 and 12 months of age but decreased significantly in old rats. V did not show significant age-dependent differences. CONCLUSION: The present findings further extend the results of our previous studies on the ultrastructure of synaptic mitochondria and support the concept of marked metabolic impairment as a basal detrimental condition in the process of brain aging. As a marker of metabolically active mitochondria at high rates of cellular respiration, our present data document that with advancing age the number of efficient organelles decreases and that this may be of critical importance for the proper function of nerve cells when the energy demand is high.

Aging↗
PubMed1996

Deterioration threshold of synaptic morphology in aging and senile dementia of Alzheimer's type.

OBJECTIVE: To search for a deterioration threshold of synaptic ultrastructure in physiologic aging and senile dementia of Alzheimer's type (SDAT). STUDY DESIGN: The numerical density (Nu), average area (S) and surface density (Su) of the synaptic contact zones were investigated in the hippocampus and cerebellum from adults, elderly and SDAT patients by means of computer-assisted morphometry. RESULTS: The Nu and surface Su densities of the synapses decreased while the size of S enlarged in elderly and SDAT patients vs. the adults. By plotting Nu vs. S, the adult group showed a very high percentage of small junctions. In contrast, elderly and dementia patients demonstrated two overlapping populations of enlarged contacts. In SDAT the synapse-to-neuron ratio was decreased by 48% in the hippocampus and by 56% in the cerebellum. CONCLUSION: Our findings support the concept that the degeneration of synaptic contacts per se should be considered a crucial step in the progression of senile dementia, but the identification of a discrete deterioration threshold of synaptic morphology between aging and SDAT is not feasible at present.

Aged↗
PubMed1995

Rectal suction biopsy: can it be sufficient to diagnose neuronal intestinal dysplasia?

Rectal suction biopsy is the diagnostic procedure of choice in aganglionosis even if only mucosal tissue is obtained. In neuronal intestinal dysplasia it is essential to include parts of the submucous layer. Therefore some biopsies are unsuitable because they lack submucous tissue. In a retrospective analysis (1991-1993) this occurred in 34.9% of our biopsies. These samples were taken without attention to the level of suction. Prospectively we compared suction biopsies taken by a standard suction level (250-300 cm water column) with excision biopsies taken by scissors under speculum exposure in ten consecutive patients. Submucosa was missed in only one biopsy each, but two excision biopsies were made useless by mechanical traumatization. We conclude a correctly practised rectal suction biopsy still remains the procedure of choice for diagnostic screening in malformations of the enteric nervous system.

Biopsy↗
PubMed1995

Vitamin E deficiency as a model of precocious brain aging: assessment by X-ray microanalysis and morphometry.

Vitamin E (alpha-tocopherol) is a known biological antioxidant able to quench the lipid peroxidation chain and to protect the cellular structures (e.g., plasma membranes) from the attack of free radicals which are reported to play a primary role in aging. To assess whether the absence of alpha-tocopherol from the diet of young laboratory animals may be considered a reliable model of precocious brain aging, intracellular ionic content of brain cortex pyramidal cells, ultrastructural features of synaptic contact zones, synaptic mitochondria and perykarial mitochondria positive to the succinic dehydrogenase (SDH) histochemical reaction with copper ferrocyanide have been investigated by X-ray microanalysis and computer-assisted morphometry in young, adult, old and 11-month-old vitamin E deficient rats. Our data document significant alterations of intracellular ionic content, synaptic contact areas and synaptic and perykarial mitochondria in aging. Vitamin E deficiency caused similar alterations in adult animals. Taking into account the known role of alpha-tocopherol in protecting the cellular membrane structure, we support that the common process underlying the changes found in aging and vitamin E deficiency is an excessive deterioration of the neuronal membrane.

Aging↗
PubMed1994

What is primary and what secondary for amyloid deposition in Alzheimer's disease.

The fact that physiologically beta-amyloid precursor proteins are synthesized by all cells of the body without any amyloid deposition in other organs raises a question about an isolated deposition of amyloid in the brain. One of the most important mechanisms in the pathogenesis of senile dementia of the Alzheimer type is the marked decrease of the cerebral glucose metabolism, a cholinergic deficit, by a disturbed acetyl-CoA synthesis and a critically lowered oxidative phosphorylation. Remembering that aging is the most important predisposing factor in the development of Alzheimer's disease, it is argued that a decrease of the oxidative energy metabolism in senile dementia and the resulting ATP deficit may change protein degradation, synaptic transmission and ion homeostasis. Therefore, a more than 50% decline of oxidative energy turnover could be a trigger for an accumulation of beta-amyloid in the brain, because the degradation of beta-amyloid precursor protein could be directly or indirectly disturbed by an ATP deficit. Amyloidosis and a cholinergic deficit in SDAT would then be a secondary phenomenon of the decreased glucose metabolism in the brain.

Aged↗
PubMed1994

Hirschsprung's disease and allied disorders--a review.

Despite scepticism in the English speaking literature today there is international agreement on the existence of neuronal intestinal dysplasia and other intestinal malformations which may well be differentiated from classical aganglionosis. In large series of patients with neuronal intestinal malformations it was found that only one fourth suffers from Hirschsprung's disease. Therefore this article presents the state of our recent knowledge of classical aganglionosis and allied disorders which include hypoganglionosis, neuronal intestinal dysplasia type A and B, immaturity of ganglion cells and not classifiable dysganglionosis. We want to emphasize the morphological differentiation of these neuronal intestinal malformations. However, the relationship between morphological findings, clinical symptoms and bowel motility remain to be clarified by further studies.

Child↗