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L T Larsson

Publications and source records attributed to L T Larsson.

28 records · Page 2Linked to original sources

Intestinal endocrine cells in Hirschsprung's disease. No reduction in density in aganglionic compared with ganglionic segment.

The aganglionic intestine in Hirschsprung's disease displays a severe neuronal derangement. The changes are particularly evident in the muscular innervation. In the gut the endocrine cells are among the cells known to be influenced by neurons. We have, therefore, examined the endocrine cells in ganglionic and aganglionic intestine using immunocytochemistry and immunochemistry. The endocrine cells were studied using antibodies against the neuroendocrine marker chromogranin A, the amine serotonin and the hormonal peptides somatostatin, glucagon/glicentin and peptide YY (PYY), thus covering virtually all endocrine cell types known to occur in this region. The PYY concentration in the mucosal layer was measured by radioimmunoassay. In ganglionic as well as in aganglionic intestine large populations of cells storing chromogranin A, serotonin, glucagon and PYY and a smaller population of somatostatin cells were seen. There was an increase in the density of these cells in the aganglionic intestine compared with ganglionic. The data indicate that the endocrine cell populations in the intestinal wall can be maintained despite severe derangements of the nerve supply.

Cell Count↗

Is the reduction of VIP the clue to the pathophysiology of Hirschsprung's disease?

The reduction of vasoactive intestinal peptide-(VIP) containing nerve fibres in the aganglionic segment in Hirschsprung's disease is thought to contribute to the sustained contraction of this intestinal segment. In order to study the significance of VIP in the pathogenesis of Hirschsprung's disease we used immunohistochemistry to evaluate the reduction of VIP-immunoreactive nerve fibres in aganglionic intestine compared to the ganglionic one. The VIP nerve fiber density was compared with the type of onset of disease (e.g. neonatal ileus or obstipation) and with the length of the aganglionic segment. No statistically significant correlation between these factors could be registered. This indicates a high complexity of the neuronal derangement in aganglionic intestine and that the degree of VIP deficiency alone does not correlate with the severity of the disease.

Colon↗

Neuronal markers in Hirschsprung's disease with special reference to neuropeptides.

Hirschsprung's disease (Megacolon congenitum) is characterized by a sustained contraction of a segment of the large intestine and a consequent enlargement of the preceding gut segment. Morphologically, Hirschsprung's disease is characterized by an absence of neuronal cell bodies in the intramural ganglia of the contracted segment. An additional characteristic finding is the presence of enlarged nerve trunks in the submucosa and in the layer separating the circular and longitudinal muscle layers. These nerve trunks contain abundant acetylcholine esterase (AChE)-positive nerve fibers. The nerve fiber hyperplasia together with an increased amount of acetylcholine as well as AChE activity in the aganglionic segment suggests a cholinergic hyperinnervation. There are other reports claiming an adrenergic hyperinnervation in the aganglionic segment. Recent studies on the peptidergic innervation of the afflicted intestinal segment have demonstrated marked reduction in the density of nerve fibers storing vasoactive intestinal peptide (VIP), substance P (SP), enkephalin and gastrin releasing peptide (GRP). The frequency of nerve fibers storing calcitonin gene-related peptide (CGRP) and galanin seems less affected. Interestingly, nerve fibers storing neuropeptide Y (NPY) are more frequent than normally in the aganglionic segment, the circular muscle being penetrated by numerous NPY-containing nerve fibers. Thus, neuropeptides have turned out to be interesting and promising new markers in the histochemical diagnosis of Hirschsprung's disease. Other possibilities for the histochemical diagnosis includes the immunocytochemical demonstration of general neuronal markers such as neurospecific enolase (NEC), neurofilament and chromogranins. Techniques demonstrating the cholinergic and adrenergic hyperinnervation in the aganglionic intestine such as AChE staining and staining for adrenergic nerves are also of interest for the diagnosis.

Biomarkers↗

Late surgical problems in children born with abdominal wall defects.

During a 17 year period 55 patients with abdominal wall defects were treated. A questionnaire concerning late surgical problems was distributed to the parents of the 47 surviving children and 44 (94%) answers were received. The mean follow up time was 5.4 years. There was no mention of remaining problems regarding 16 of the 28 omphalocoele patients and 10 of the 16 gastroschisis patients. Postoperative abdominal wall hernia was reported in 7 cases with omphalocoele and in 6 with gastroschisis; postoperative intestinal stoma occurred in 1 child with omphalocoele associated with anal atresia, and in 1 with gastroschisis and postoperative intestinal obstruction in 4 cases with omphalocoele and in 1 with gastroschisis. The other complaints related to abdominal pain, cryptorchidism, constipation and difficulties with care of the intestinal stoma. No difference in results was found between the two types of closure of the abdominal wall defects irrespective of the primary treatment. All the remaining problems could be corrected and the long term results in both conditions were good.

Abdominal Muscles↗

Neuropeptide Y, calcitonin gene-related peptide, and galanin in Hirschsprung's disease: an immunocytochemical study.

The aganglionic intestinal segment in Hirschsprung's disease is known to contain a reduced number of nerve fibers storing vasoactive intestinal peptide (VIP), substance P (SP), enkephalin, and gastrin-releasing peptide (GRP). In this study, nerves containing three newly described neuropeptides: neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and galanin were examined using immunocytochemistry. Nerve fibers displaying NPY immunoreactivity were found to be more frequent in the aganglionic than in nonafflicted ganglionic intestine. Nerve fibers storing CGRP and galanin on the other hand were roughly equally frequent but the distribution pattern differed in that the bulk of fibers in the aganglionic intestine was localized to large nerve trunks not seen in the ganglionic segment. The functional significance of these changes has yet to be defined.

Calcitonin↗

Ontogeny of peptide-containing neurons in human gut--an immunocytochemical study.

Neurons containing enkephalin, substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), galanin, calcitonin gene-related peptide (CGRP), peptide histidine isoleucine (PHI) or gastrin-releasing peptide (GRP) are known to occur in the human intestinal tract. The knowledge of the ontogeny of these neurones is, however, limited. Intestinal specimens from 24 human foetuses with gestational ages varying between 8 and 40 weeks were examined by immunocytochemistry. No peptide-containing neurones could be detected before the 14th week of gestation after which a rapid development was seen. Generally, peptide immunoreactivity was first noted in the myenteric ganglia and somewhat later in the other layers of the intestinal wall. There was no major difference between the peptides studied or between different parts of the intestinal tract with respect to time of appearance.

Calcitonin Gene-Related Peptide↗

Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro.

Specimens from aganglionic (constricted) and ganglionic (dilated) gut were obtained from nine patients with Hirschsprung's disease. Transmural nerve stimulation of ganglionic smooth muscle in vitro evoked an initial relaxation followed by a contraction. This contraction was reduced but not abolished by atropine and it was further reduced by substance P antagonists. Guanethidine did not affect the electrically evoked responses. In aganglionic smooth muscle, an atropine-sensitive contraction but no initial relaxation was registered. Tetrodotoxin abolished all responses to electrical stimulation in both ganglionic and aganglionic specimens. Application of carbachol or substance P produced contraction and the adrenergic agonist isoprenaline or vasoactive intestinal peptide produced relaxation in ganglionic as well as aganglionic specimens. Two other gut neuropeptides, neuropeptide Y and galanin, were without effect. The results do not indicate a different receptor set up in ganglionic v aganglionic gut. The results are compatible with a lack of noncholinergic nonadrenergic inhibitory neurons in the aganglionic gut.

Child↗

The advantage of antenatal diagnosis of intestinal and urinary tract malformations.

In a 24-month prospective screening programme 6020 pregnant women were examined with diagnostic ultrasound at 17 and 32 weeks gestation. In a total of 23 (0.38%) abnormalities, four cases of urinary tract and two of intestinal tract abnormalities were discovered. The antenatal diagnosis influenced the management of these disorders both before and after birth.

Abdominal Muscles↗

Peptidergic innervation in Hirschsprung's disease.

An increasing amount of evidence concerning the existence of non-adrenergic, non-cholinergic autonomous nerves has been presented during the past decade. These nerves contain different peptides which may act as neurotransmitters. The pathophysiology in Hirschsprung's disease is not yet fully explained. To throw further light upon it, the distribution and occurrence of different peptide-containing (peptidergic) nerves was studied. A semiquantitative immuno-histochemical method was used to assess the distribution and occurrence of nerves containing encephalin, GRP (gastrin-releasing peptide), VIP (vasoactive intestinal peptide) or substance P in four patients operated by Duhamel's procedure. The results indicate a total absence of encephalin and GRP containing nerves in the aganglionic segment. Such nerves could, however, be found in the normally ganglionated part of colon. The nerves containing VIP and substance P were fewer in the aganglionic segment than in the rest of the colon. The result is related to what is hitherto known about the specific effects of the different peptides.

Colon↗