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Biomedical subjects

K Norrby

Publications and source records attributed to K Norrby.

At least 73 records · Page 4Linked to original sources

Time-course and rate of healing after wounding the avascular mesentery in diabetic rats.

The effects of inflicting trauma on the mesentery of diabetic and control rats by perforation with a scalpel were studied with regard to time-course of healing and rate of healing by closure. In this tissue, which is virtually free from blood vessels and nerves, healing precedes vascularization of the wound area. Insulin-deficient rats with streptozotocin diabetes of 4 weeks' duration were used. Non-specific histamine release and cell proliferation (expressed as specific DNA activity) lasting 30 h took place after opening the abdomen and handling the mesentery. Wounding caused further histamine release and cell proliferation. These variables were the same in diabetic and control rats. The time-course of healing was significantly delayed in diabetes, whereas the rate of healing (number of wound closures per day) during the phase of rapid healing was not. Because the rate of healing was normal in diabetic rats the impairment of healing in diabetes can be ascribed to pre-healing reparative events unrelated not only to vascular and neural factors but apparently also to the amount of histamine released and to the cell proliferation elicited by wounding. The delayed healing thus seems to be related to some cellular or metabolic feature of diabetes as yet unknown.

Animals↗

Radiation effects on mast cells: secretory ability, histamine release and recovery, and cell number.

We studied the effects of irradiation with a single fraction of high-energy electrons, in the absorbed dose range used in radiotherapy, on features related to the rat mesenteric mast-cell (MC) population. Such features were energy dispersive X-ray microanalysis for zinc, light and transmission electron microscopic changes, histamine content, and secretory ability of MCs when exposed to the potent secretagogue 48/80. The observation period was 14 days. Also studied were the effects of radiation on the number and histamine content of free peritoneal MCs. Irradiation-induced decrease in histamine content was delayed for at least two days and the rate of subsequent recovery of mesenteric histamine was approximately 70% below normal. This was corroborated by the findings of necrotic and fragmented mesenteric MCs during the entire experimental period. Fibroblasts and macrophages phagocytosed groups of MC granules as well as individual MC granules. A fraction of the extruded MC granules retained an almost normal appearance. This suggests that they were solubilized unduly slow presumably because the irradiation destroyed the mechanisms and enzymes which normally degrade the heparin-protein granule matrix and its heparin. Moreover, the irradiation suppressed the secretory ability of mesenteric MCs and significantly reduced the number of free peritoneal MCs. The findings indicate that the MC is a remarkably radiosensitive connective-tissue cell.

Animals↗

Intestinal intramural haemorrhage after abdominal missile trauma--clinical classification and prognosis.

Various types of abdominal trauma, such as penetrating missile wounds, blast and severe blunt force, can cause haemorrhage within the intestinal wall. Such bleeding often is multi-sited. In a previous study on anaesthetized pigs subjected to missile trauma, the microscopic appearance of the lesions was described. Risk of perforation, even in lesions of primarily innocent appearance, was also demonstrated, in accordance with reports in the literature. The present study aimed to find a method for predicting which of such haemorrhages may be left untreated and which must be excised. For this purpose, 85 anaesthetized pigs were subjected to low-velocity missile injury to the abdomen. All intramural haemorrhages of the intestine without primary perforation was thereafter classified at laparotomy according to a few easily observed macroscopic criteria. The anaesthesia was maintained and the classification was compared with findings at a second laparatomy at the end of the observation period (maximum 4 days), when histologic study also was performed. The macroscopic criteria showed good correspondence with histologically observed mucosal ulceration and muscle damage. In 64% of the lesions there was macroscopic progression during the observation time, with perforation in 5.4%. Lesions with mean diameter larger than 10 mm, visible serosal defect and palpable mural defect carried the highest perforation risk (16%). Lesions fulfilling none of these criteria did not perforate. The study confirmed the risk of secondary intestinal perforation in primarily non-perforating intramural haemorrhage following abdominal trauma. The results also suggest that some simple macroscopic criteria may be useful for predicting this risk.

Abdominal Injuries↗

Fluorescein angiography in the evaluation of intestinal intramural haemorrhage after trauma.

Intramural hemorrhage of the intestines occur after different types of abdominal trauma. These haemorrhages may lead to secondary perforation and peritonitis. As the bleeding often is multifocal, radical resections would entail correspondingly many anastomoses, with increased risk of complications. A method for macroscopic recognition of perforation risk was described in a previous report. The macroscopic criteria used in that classification have now been compared with a vital staining technique, involving intravenous injection of fluorescein. The fluorescence patterns of 'non-viability' accorded well with histologically observed damage to the muscular layer of the gut and with transmural devitalization. There was also good correlation with the macroscopic criteria in the previous classification, but the fluorescein method was higher predictive of transmural devitalization. When the methods were combined, the detection of dangerous lesions was still improved. Fluorescein staining is clinically applicable, and thus can be a valuable complement for discerning heightened risk of perforation in intestinal intramural haemorrhages.

Abdominal Injuries↗

Intestinal intramural haemorrhage after blunt abdominal trauma.

Intramural haemorrhage of the intestine following blunt trauma to the abdomen has been described in several clinical studies. Though such lesions may have an innocent appearance at primary laparotomy, they lead to delayed intestinal perforation in some cases. In previous experiments with similar lesions produced by penetrating abdominal missile, the histologic appearance and the clinical course were documented in pigs observed under long-term anaesthesia. In the present study anaesthetized pigs were submitted to blunt abdominal trauma in an impact machine, whereby the impact velocity could be regulated. The intra-abdominal pressure and the delivered impulse were recorded and the incidence and histologic appearance of intestinal injuries were observed at laparotomy immediately after the trauma. Intramural haemorrhage was found to occur when the impact velocity exceeded 5 m/s. At impact velocity 20 m/s, intestinal rupture occurred primarily. The observed intramural haemorrhages had the same histologic appearance as those seen after penetrating missile injury. The same clinical course, consequently, could be anticipated after blunt trauma.

Abdominal Injuries↗

The effect of insulin on delayed augmented mast-cell mediated mitogenesis in diabetic rats.

Delayed augmented mitogenic reactivity follows mast-cell secretion in mesentery and skin in streptozotocin-diabetic rats with 4-week insulin-deficiency (Norrby 1982; Norrby et al. 1982; Norrby 1983). In such rats the basal proliferation is essentially unchanged in the mesentery and skin, whereas it is significantly increased in the small gut and significantly decreased in the kidney. On treating rats with 4-week-old diabetes with very-long-acting insulin for over 3 days (16 U/kg X 2 daily) the basal proliferation of the small gut and the kidney apparently became normal, the body weight increased, and the blood glucose concentration dropped substantially and progressively. However, insulin-treatment did not affect the mast-cell-dependent mitogenesis in the mesentery following intraperitoneal injection of the mast-cell secretagogue compound 48/80, as judged by specific DNA activity and mitosis counting. We conclude that some metabolic or cellular feature of diabetes which is not restored by 3-day insulin treatment, and not insulin deficiency itself, is the cause of the delayed increased mitogenic reactivity that follows mast-cell secretion in diabetic rat.

Animals↗

Normal mitotic reactivity of fibroblasts and mesothelial cells in thrombocytopenic rat.

Mitotic reactivity following 48/80-induced mast-cell secretion was studied in the mesentery of rats made thrombocytopenic, 7 days following a single injection of melphalan. In spite of a low platelet count (7% of normal), the mitogenic reaction of the mesenteric fibroblasts and mesothelial cells was normal as judged by DNA-synthesis and mitotic index. The findings suggest that platelets and platelet-growth factors are not essential for the mast-cell-mediated mitogenic reaction of these two types of connective-tissue cells studied in vivo.

Animals↗

Intradermal mast-cell secretion causing cutaneous mitogenesis.

This study demonstrated that mast-cell secretion elicited by intradermal injection of compound 48/80 initiated cell proliferation in rat skin. The mast-cell secretion was confirmed by microscopical demonstration of degranulation of mast cells, and by quantifying histamine release, whereas the proliferation was assessed by measuring DNA-synthesis and the frequency of mitosis. The results, which fully support our previous findings in the true mesentery, indicate that the common type of mast cell, when appropriately activated, is capable of playing a role in governing cell proliferation in diverse tissues.

Animals↗

Malignant carcinoid tumour complicating coeliac disease.

A man with coeliac disease diagnosed in adult life developed a malignant carcinoid tumour in the ileum. Although previously unreported, the association may not be fortuitous in the light of recent observations showing consistent abnormalities in the enterochromaffin cell population in the damaged coeliac mucosa.

Aged↗

Hyperplasia and growth of the true mesentery in the diabetic rat.

The true mesentery was studied in rats 4 weeks after they had been rendered diabetic with streptozotocin. The diabetic animals showed elongation and enlargement of the small intestine despite reduced body growth compared with controls of the same age. The mesentery in diabetic animals showed increased total area and contained an increased number of "windows", but the increment of total protein, DNA, and histamine (a marker of mast cells) was non-uniform and less than the increase in area. There appeared to be a close relationship between hyperplasia of the small intestine and its mesentery. The number of mast cells yielded by peritoneal lavage was increased in the diabetics. We suggest that our observation of the hyperplastic mesenteric reaction in diabetic rats may make a useful model for the study of growth, profiferation, and function of the mesentery available.

Animals↗

A tissue model for quantitative studies on time course of healing, rate of healing, and cell proliferation after wounding.

The perforated true mesentery of the rat was exploited as a model for the quantitative study of connective tissue wound healing. Healing by closure was examined daily after the virtually-vessel-free mesentery had been perforated with a scalpel. Proliferation was quantitated in fibroblast- and mesothelial-like cells in spreads of mesentery at defined distances from the wound margin, by means of cytophotomeric Feulgen-DNA measurements and by mitotic counting. Proliferation was also estimated by specific DNA-activity in perforated and unperforated mesentery membranes. Mast-cell histamine was quantitated as an indicator of disturbed tissue homeostasis. In young rats, healing by closure started on day 4, and was complete on day 10. The maximum rate of healing occurred on days 5-7. Old animals showed essentially the same rate of healing as young ones but healing was significantly delayed. Sham-operated animals showed a moderate release of histamine and increased proliferation. Wounding caused additional release of histamine and was followed by increased proliferation after 48-96 h. With this novel procedure, the time course, the rate of healing, and the proliferation of cells at defined distances from the wound can be defined quantitatively. The technique may well prove valuable in the study of the interplay between proliferation and healing and in the study of the effect of local and systemic factors on connective tissue wound healing.

Aging↗

Effect of elevated substrates on substrate oxidation in normal and diabetic aorta.

The influence of elevated substrates (glucose, beta-hydroxybutyrate and palmitate) on the gated. The oxidation of 14C-glucose to 14CO2 was depressed in diabetic aorta at a glucose concentration of 5.6 mM in the incubation medium. The glucose oxidation in normal and mM. The oxidation of 14C-beta-hydroxybutyrate (0.5 and 1.5 mM) to 14CO2 was impaired in diabetic aorta, while the oxidation of 14C-palmitate (0.5 and 1.0 mM) to 14CO2 was unaltered. The oxidation of both substrates was concentration dependent. The glucose oxidation in normal rat aorta was reduced by addition of 3.0 and 6.0 mM of beta-hydroxybutyrate to the incubation medium, while 1.5 mM palmitate had no effect on the glucose oxidation. After incubation of normal rat aorta in MEM with glucose (20.0 mM) for 46 h the subsequently determined glucose oxidation was not influenced in comparison to the aorta incubated in 5.6 mM glucose. Incubation with 6.0 mM beta-hydroxybutyrate or 1.5 mM palmitate did not affect the aortic glucose oxidation. In rats which were infused for 24 h with glucose or beta-hydroxybutyrate to obtain diabetic levels of these substrates, there was no change in the aortic glucose oxidation compared to saline-infused controls. The present results suggests that the lowered glucose oxidation in diabetic vascular tissue is not caused by hyperglycemia or high concentrations of ketone bodies or free fatty acids in the diabetic state.

3-Hydroxybutyric Acid↗

Similar prevalence of coeliac disease in children and middle-aged adults in a district of Sweden.

Coeliac disease in children and adults is considered to be a variety of the same disorder. This gains epidemiological support in the present study, which reports on the observed prevalence of coeliac disease in an area of Sweden (population, 140 500). On 1 July 1981, the prevalence rate was found to be 104/100 000 (1:960) among children, and the same figure, 106/00 000 (1:950), was found for coeliac disease unaccompanied by dermatitis herpetiformis in the middle-aged population. The figures were obtained in patients seeking medical are and thus represent minimum rates, and it is likely that the actual prevalence of coeliac disease in Sweden will prove still higher.

Adolescent↗

Raised 5-hydroxytryptamine concentrations in enterochromaffin cells in adult coeliac disease.

We measured cytofluorometrically the concentration of 5-hydroxytryptamine (5-HT, serotonin) of individual enterochromaffin (EC) cells in adult coeliac and non-coeliac small intestinal mucosa. The distributions of 5-HT concentration within populations of EC cells in control and coeliac mucosae were log normal and thus contained one single population of EC cells. The median 5-HT concentration per EC cell, and the number of EC cells both increased in coeliac disease, but showed signs of normalisation when gluten was withdrawn from the diet. The results indicate that, besides inducing EC cell hyperplasia, gluten is capable of producing reversible changes in functions of EC cells in adult coeliac disease.

Adult↗

Are the clinically important adrenal cysts hamartomas?

An adrenal cyst in a 36-year-old apparently healthy woman was diagnosed as a hamartoma with haemangiomatous structures and a large cyst, probably secondary to haemorrhage within the lesion. After reviewing the histological records of all the previously published cases of similar "haemorrhagic" non-inflammatory adrenal cysts, the aetiology of which has been considered unclear, we conclude that they too were probably hamartomas. We therefore propose that this type of adrenal cyst, the only of clinical importance, is aetiologically a hamartoma. These tumours often show super-imposed degenerative post-haemorrhagic changes.

Adrenal Gland Diseases↗

Delayed mast cell mediated mitogenic reactivity in diabetic rats.

Rats with diabetes of 4 weeks' duration have previously demonstrated increased mitogenesis in normal connective tissue cells following mast cell secretion. The appearance of this augmented mast cell-mediated mitogenic reactivity was studied in the mesentery of insulin-deficient rats, 3, 7, and 28 days after they had been rendered diabetic by a single dose of streptozotocin. On day 7 mast cell secretion induced a subnormal mitogenic response which, however, increased above normal on day 28. This time lag in the augmentation of mitogenic responsiveness may be important since proliferative lesions in diverse mesenchymal tissues typically develop with a similar delay in both experimental and clinical diabetes.

Animals↗