Manganese chloride (MnCl2), with or without the addition of trace amounts of 54Mn2+, was administ... more Manganese chloride (MnCl2), with or without the addition of trace amounts of 54Mn2+, was administered as a 7-min i.v. infusion in rats. Tissue accumulation of 54Mn2+ was determined 0-15 min after the infusion, and cardiac output, regional blood flows and vascular resistances were measured 5 and 60 min after the infusion by the microsphere technique. The plasma half-life of 54Mn2+ was found to be 4.7 min. Mn2+ accumulated in several organs, the highest relative concentrations being seen in the liver, duodenum, jejunum, kidney and heart, and intermediate concentrations in the ileum, colon, stomach and spleen. There was no uptake in the lung, skeletal muscle or brain. During the infusion of 180 mumol/kg b.w. of Mn2+, the arterial blood pressure fell from a mean of 123 +/- 5 mm Hg to a minimum of 85 +/- 7 mm Hg, and thereafter returned to normal. Five minutes after termination of the infusion, there was a decrease in cardiac output and minute work but not in total peripheral resistance,...
Infusion of thrombin and the fibrinolysis inhibitor tranexamic acid during ether anaesthesia in t... more Infusion of thrombin and the fibrinolysis inhibitor tranexamic acid during ether anaesthesia in the rat gives rise to fibrin deposition in the renal glomeruli. This resulted in renal insufficiency as indicated by an increase in the serum urea nitrogen, reduction in the renal blood flow and patchy cortical necrosis in the kidneys. The plasma renin activity was elevated initially probably due to the ether anaesthesia. Infusion of the angiotensin II antagonist saralasin prevented the renal insufficiency if it was given during the thrombin infusion but not if it was given afterwards. The deposition of fibrin in the kidneys was also reduced. The results indicate that angiotensin II is involved in the pathogenesis of the renal injury.
Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigate... more Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA were given, separated by 90 min washout periods. Blood samples were taken before, during and after each infusion and the plasma HA concentration was determined. The deposition of HA was modelled according to a Michaelis–Menten kinetic model which included natural synthesis of HA. Km and Vmax was estimated to 0·34 ± 0·13 μgml‐1 and 3·48 ± 0·97/μmin‐1kg‐1 b.w., respectively. The endogenous input was calculated to be 24 ± 11 μg min‐1 and was found to correlate to the age of the subjects (P < 0·05). As the baseline HA concentration was 0·031 ± 0·21 μg ml‐1, the rate of elimination was linear in the normal concentration range. The calculated Vd was about 75% higher than a weight‐estimated plasma volume. The total amount of HA excreted by the kidneys during the study period was 394 ± 77 μg, which corresponded to approximately 1·7% of the total input of HA into the circulation during the experiment.
Laboratory investigation; a journal of technical methods and pathology, 1993
The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal acti... more The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear. The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively. All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive ...
The effect of reversible cerebral ischaemia on brain oedema development was studied with a gravim... more The effect of reversible cerebral ischaemia on brain oedema development was studied with a gravimetric method. Cerebral blood flow changes after ischaemia were correlated with alterations in brain specific gravity. Forebrain ischaemia (15 min) was induced in rats by reversible bilateral ligation of both carotid arteries plus induction of controlled hypotension to 50 mm Hg. The specific gravity of different brain structures was determined in a Percoll column up to 24 h after ischaemia. In addition, regional cerebral blood flow was measured by 14C-iodoantipyrine autoradiography. Cerebral ischaemia resulted in reduction of cerebral blood flow to less than 1% of normal in cortical structures and the caudatoputamen. One hour after the end of ischaemia blood flows were still reduced to 30-50% of the control level indicative of delayed postischaemic hypoperfusion. Specific gravity in cortex and hypothalamus reached a maximal decrease 10 min after the end of the ischaemia, and was still significantly reduced at 1 h, while it was normal again 6 hrs later. Regression analysis between regional cerebral blood flows and the corresponding specific gravities were made at various time points, but no significant correlations could be established. Other mechanisms, like vasoconstriction, rheologic or metabolic factors may be causative for the delayed postischaemic hypoperfusion.
OBJECTIVE To evaluate the results after Delorme's operation for rectal prolapse in elderly an... more OBJECTIVE To evaluate the results after Delorme's operation for rectal prolapse in elderly and unfit patients. DESIGN Retrospective analysis and telephone interview. SETTING Akademiska sjukhuset, Uppsala, Sweden. SUBJECTS A consecutive series of 14 women (median age 82, range 32-92) operated on for rectal prolapse 1987-1992 and followed up after a median of 18 months. RESULTS There were no serious postoperative complications. Continence was improved in 6/11 incontinent patients. The recurrence rate was 3/14 (21%). CONCLUSION Delorme's operation is an attractive alternative in elderly or unfit patients, but is not recommended for younger and low risk patients because of the recurrence rate.
Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be... more Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn&amp;amp;#39;s disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p &amp;amp;lt; 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.
A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the int... more A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the intestinal tract were retrospectively reviewed and clinical and surgical factors were related to the ultimate prognosis by multivariate analysis. The first operation was performed on the small intestine in 47 patients, the large intestine in 32 patients or both in nine patients. Postoperative complications occurred in 35 patients (40%), with fatal outcome in 12 (13%). Thirty-one patients (35%) required further surgery and altogether 19 patients (22%) ultimately died from RID. Negative prognostic factors after the first operation were postoperative intestinal leak (P &lt; 0.05) and operation for fistula or perforation (P &lt; 0.01). The outcome after the last operation was negatively influenced by intestinal leak (P &lt; 0.001) by the choice of bypass as operative procedure (P &lt; 0.01) and by operation for fistula or perforation (P &lt; 0.01). In addition, 43% of the patients in whom the disease had progressed between two explorations died from RID. Thus, the severity of the RID as diagnosed at laparotomy, and progression of the disease between two subsequent explorations were related to the prognosis. Care should be taken to avoid intestinal leak. Resections should be preferred to bypass of injured intestine whenever possible.
ABSTRACT The accumulation, distribution and luminal secretion of hyaluronan (hyaluronic acid; HA)... more ABSTRACT The accumulation, distribution and luminal secretion of hyaluronan (hyaluronic acid; HA) was demonstrated at different times after small bowel transplantation experimentally, and in one clinical case. Semiallogenic or semisyngenic rat models were used to elicit either unidirectional graft rejection or graft-versus-host disease. During graft rejection a cellular infiltrate and edema appeared in the lamina propria in the crypt are where an accumulation of HA was also demonstrated. There was progressive accumulation of HA in the small bowel during rejection and on day 6 there was a three-fold increase compared to the values in syngenic grafts. The increase in tissue HA was paralleled by an increase in the total water content of the rejecting graft. Measurements of the luminal secretion of HA in rejection grafts at day 6 revealed a five fold increase at this time. In specimens from animals suffering from GVHD, no significant changes in water of HA content and distribution were observed until day 12. In a clinical case of small bowel transplantation in a 14 months oldchild, luminal secretion of HA was measured in the graft by using a segmental intestinal perfusion technique. A more than 30 fold increase of secreted HA was noted, which was directly paralleled by clinical and histological signs of graft rejection. The data suggest that accumulation of HA might contribute to the pathophysiology of the transplantation edema and that HA might be of potential diagnostic value for monitoring purposes after small bowel transplantation.
The effect of acute haemorrhage on the deposition and clearance of fibrin in the rat lung after t... more The effect of acute haemorrhage on the deposition and clearance of fibrin in the rat lung after thrombin-induced intravascular coagulation was investigated. Haemorrhage was followed by less embolization of fibrin to the lungs and delayed elimination from the lungs. As lung tissue fibrinolysis was not diminished, the peripheral and pulmonary circulatory disturbance was probably in itself responsible for the observed effects.
Closure of the abdomen after surgery has been performed in a multitude of fashions and the litera... more Closure of the abdomen after surgery has been performed in a multitude of fashions and the literature is flooded with differently tailored studies of this matter. In this paper the available literature in the field has been reviewed with special emphasis on the advantages and disadvantages of continuous or interrupted, mass or layered closure, and on the choice of monofilament or multifilament, resorbable or non-resorbable suture material. After weighing up all the aspects, the authors recommend that the abdomen should be closed with a continuous mass closure technique, using a monofilament suture. No firm conclusion can be drawn from the literature as to whether resorbable or non-resorbable suture should be chosen.
Manganese chloride (MnCl2), with or without the addition of trace amounts of 54Mn2+, was administ... more Manganese chloride (MnCl2), with or without the addition of trace amounts of 54Mn2+, was administered as a 7-min i.v. infusion in rats. Tissue accumulation of 54Mn2+ was determined 0-15 min after the infusion, and cardiac output, regional blood flows and vascular resistances were measured 5 and 60 min after the infusion by the microsphere technique. The plasma half-life of 54Mn2+ was found to be 4.7 min. Mn2+ accumulated in several organs, the highest relative concentrations being seen in the liver, duodenum, jejunum, kidney and heart, and intermediate concentrations in the ileum, colon, stomach and spleen. There was no uptake in the lung, skeletal muscle or brain. During the infusion of 180 mumol/kg b.w. of Mn2+, the arterial blood pressure fell from a mean of 123 +/- 5 mm Hg to a minimum of 85 +/- 7 mm Hg, and thereafter returned to normal. Five minutes after termination of the infusion, there was a decrease in cardiac output and minute work but not in total peripheral resistance,...
Infusion of thrombin and the fibrinolysis inhibitor tranexamic acid during ether anaesthesia in t... more Infusion of thrombin and the fibrinolysis inhibitor tranexamic acid during ether anaesthesia in the rat gives rise to fibrin deposition in the renal glomeruli. This resulted in renal insufficiency as indicated by an increase in the serum urea nitrogen, reduction in the renal blood flow and patchy cortical necrosis in the kidneys. The plasma renin activity was elevated initially probably due to the ether anaesthesia. Infusion of the angiotensin II antagonist saralasin prevented the renal insufficiency if it was given during the thrombin infusion but not if it was given afterwards. The deposition of fibrin in the kidneys was also reduced. The results indicate that angiotensin II is involved in the pathogenesis of the renal injury.
Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigate... more Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA were given, separated by 90 min washout periods. Blood samples were taken before, during and after each infusion and the plasma HA concentration was determined. The deposition of HA was modelled according to a Michaelis–Menten kinetic model which included natural synthesis of HA. Km and Vmax was estimated to 0·34 ± 0·13 μgml‐1 and 3·48 ± 0·97/μmin‐1kg‐1 b.w., respectively. The endogenous input was calculated to be 24 ± 11 μg min‐1 and was found to correlate to the age of the subjects (P < 0·05). As the baseline HA concentration was 0·031 ± 0·21 μg ml‐1, the rate of elimination was linear in the normal concentration range. The calculated Vd was about 75% higher than a weight‐estimated plasma volume. The total amount of HA excreted by the kidneys during the study period was 394 ± 77 μg, which corresponded to approximately 1·7% of the total input of HA into the circulation during the experiment.
Laboratory investigation; a journal of technical methods and pathology, 1993
The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal acti... more The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear. The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively. All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive ...
The effect of reversible cerebral ischaemia on brain oedema development was studied with a gravim... more The effect of reversible cerebral ischaemia on brain oedema development was studied with a gravimetric method. Cerebral blood flow changes after ischaemia were correlated with alterations in brain specific gravity. Forebrain ischaemia (15 min) was induced in rats by reversible bilateral ligation of both carotid arteries plus induction of controlled hypotension to 50 mm Hg. The specific gravity of different brain structures was determined in a Percoll column up to 24 h after ischaemia. In addition, regional cerebral blood flow was measured by 14C-iodoantipyrine autoradiography. Cerebral ischaemia resulted in reduction of cerebral blood flow to less than 1% of normal in cortical structures and the caudatoputamen. One hour after the end of ischaemia blood flows were still reduced to 30-50% of the control level indicative of delayed postischaemic hypoperfusion. Specific gravity in cortex and hypothalamus reached a maximal decrease 10 min after the end of the ischaemia, and was still significantly reduced at 1 h, while it was normal again 6 hrs later. Regression analysis between regional cerebral blood flows and the corresponding specific gravities were made at various time points, but no significant correlations could be established. Other mechanisms, like vasoconstriction, rheologic or metabolic factors may be causative for the delayed postischaemic hypoperfusion.
OBJECTIVE To evaluate the results after Delorme's operation for rectal prolapse in elderly an... more OBJECTIVE To evaluate the results after Delorme's operation for rectal prolapse in elderly and unfit patients. DESIGN Retrospective analysis and telephone interview. SETTING Akademiska sjukhuset, Uppsala, Sweden. SUBJECTS A consecutive series of 14 women (median age 82, range 32-92) operated on for rectal prolapse 1987-1992 and followed up after a median of 18 months. RESULTS There were no serious postoperative complications. Continence was improved in 6/11 incontinent patients. The recurrence rate was 3/14 (21%). CONCLUSION Delorme's operation is an attractive alternative in elderly or unfit patients, but is not recommended for younger and low risk patients because of the recurrence rate.
Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be... more Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn&amp;amp;#39;s disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p &amp;amp;lt; 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.
A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the int... more A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the intestinal tract were retrospectively reviewed and clinical and surgical factors were related to the ultimate prognosis by multivariate analysis. The first operation was performed on the small intestine in 47 patients, the large intestine in 32 patients or both in nine patients. Postoperative complications occurred in 35 patients (40%), with fatal outcome in 12 (13%). Thirty-one patients (35%) required further surgery and altogether 19 patients (22%) ultimately died from RID. Negative prognostic factors after the first operation were postoperative intestinal leak (P &lt; 0.05) and operation for fistula or perforation (P &lt; 0.01). The outcome after the last operation was negatively influenced by intestinal leak (P &lt; 0.001) by the choice of bypass as operative procedure (P &lt; 0.01) and by operation for fistula or perforation (P &lt; 0.01). In addition, 43% of the patients in whom the disease had progressed between two explorations died from RID. Thus, the severity of the RID as diagnosed at laparotomy, and progression of the disease between two subsequent explorations were related to the prognosis. Care should be taken to avoid intestinal leak. Resections should be preferred to bypass of injured intestine whenever possible.
ABSTRACT The accumulation, distribution and luminal secretion of hyaluronan (hyaluronic acid; HA)... more ABSTRACT The accumulation, distribution and luminal secretion of hyaluronan (hyaluronic acid; HA) was demonstrated at different times after small bowel transplantation experimentally, and in one clinical case. Semiallogenic or semisyngenic rat models were used to elicit either unidirectional graft rejection or graft-versus-host disease. During graft rejection a cellular infiltrate and edema appeared in the lamina propria in the crypt are where an accumulation of HA was also demonstrated. There was progressive accumulation of HA in the small bowel during rejection and on day 6 there was a three-fold increase compared to the values in syngenic grafts. The increase in tissue HA was paralleled by an increase in the total water content of the rejecting graft. Measurements of the luminal secretion of HA in rejection grafts at day 6 revealed a five fold increase at this time. In specimens from animals suffering from GVHD, no significant changes in water of HA content and distribution were observed until day 12. In a clinical case of small bowel transplantation in a 14 months oldchild, luminal secretion of HA was measured in the graft by using a segmental intestinal perfusion technique. A more than 30 fold increase of secreted HA was noted, which was directly paralleled by clinical and histological signs of graft rejection. The data suggest that accumulation of HA might contribute to the pathophysiology of the transplantation edema and that HA might be of potential diagnostic value for monitoring purposes after small bowel transplantation.
The effect of acute haemorrhage on the deposition and clearance of fibrin in the rat lung after t... more The effect of acute haemorrhage on the deposition and clearance of fibrin in the rat lung after thrombin-induced intravascular coagulation was investigated. Haemorrhage was followed by less embolization of fibrin to the lungs and delayed elimination from the lungs. As lung tissue fibrinolysis was not diminished, the peripheral and pulmonary circulatory disturbance was probably in itself responsible for the observed effects.
Closure of the abdomen after surgery has been performed in a multitude of fashions and the litera... more Closure of the abdomen after surgery has been performed in a multitude of fashions and the literature is flooded with differently tailored studies of this matter. In this paper the available literature in the field has been reviewed with special emphasis on the advantages and disadvantages of continuous or interrupted, mass or layered closure, and on the choice of monofilament or multifilament, resorbable or non-resorbable suture material. After weighing up all the aspects, the authors recommend that the abdomen should be closed with a continuous mass closure technique, using a monofilament suture. No firm conclusion can be drawn from the literature as to whether resorbable or non-resorbable suture should be chosen.
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