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U H Haglund

Publications and source records attributed to U H Haglund.

9 recordsLinked to original sources

Prognosis of human pancreatic adenocarcinoma: review of clinical and histopathological variables and possible uses of new molecular methods.

Cancer of the exocrine pancreas is a disease of considerable importance in gastroenterology. In Western countries it is the fourth commonest cause of death from cancer after those of lung, colorectal, and breast. The incidence of pancreatic carcinoma has increased in Northern Europe and North America during recent decades and contrary to for example, lung, gastric and oesophageal carcinoma, its incidence is still increasing the annual incidence is about 8-10/100,000 population. The causes of its increased incidence are unknown, as is the aetiology of the disease itself. Pancreatic cancer generally grows without symptoms until late in its natural history and there are therefore many discouraging unresolved problems in management. However, some progress has been made in understanding the molecular basis of pancreatic carcinogenesis. Recent molecular pathological studies have described mutation or overexpression of important oncogenes such as K-ras and bcl-2 and deletions of tumour suppression genes such p53, DPC4, CDKN2, and the Rb gene. The present prognosis of pancreatic cancer is, however, controversial, and as these new markers may have the potential for improving our ability to predict its course, we have reviewed current knowledge, and concentrated on the classic and the recently-introduced factors in the prediction of its prognosis.

Adenocarcinoma↗

Changes in gut intramucosal pH and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.

OBJECTIVE: To establish the relationship between gut intramucosal pH and blood flow to the gut, gut oxygen delivery, and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage. DESIGN: Prospective, controlled study. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty pigs of both sexes, weighing 15 to 22 kg. INTERVENTIONS: Animals were anesthetized, intubated, and mechanically ventilated. A flow probe was placed around the superior mesenteric artery for registration of blood flow. A tonometer was placed in the lumen of midileum for calculation of gut intramucosal pH. Hourly, for 5 hrs, blood samples were taken from mixed venous, mesenteric venous, and arterial blood. Five animals served as controls, ten animals had peritonitis induced by fecal instillation in the abdominal cavity, five were bled stepwise, five were bled rapidly (to a mean arterial pressure of 30 mm Hg), and five were bled rapidly and reinfused after 3 hrs. MEASUREMENTS AND MAIN RESULTS: Both peritonitis and hemorrhage caused decreases in gut blood flow and intramucosal pH. In mild peritonitis, the intramucosal pH decrease preceded that of blood flow. In all experimental groups, oxygen delivery decreased over time; in both mild and severe peritonitis, this decrease was preceded by a decrease of intramucosal pH. Intramucosal pH correlated well with gut oxygen extraction ratio in peritonitis (r2 = .86). In hemorrhage, there was a correlation of r2 = .66, but in intramucosal pH of < 7.12, a further decrease was accompanied only by minor changes in extraction ratio. CONCLUSIONS: Since a reduction in blood flow was preceded by a decrease in intramucosal pH, low intramucosal pH in peritonitis cannot be explained by low flow alone. Gut oxygen delivery proved to be a poor indicator of gut acidosis (i.e., low intramucosal pH). In peritonitis, a decreasing intramucosal pH was associated with an increasing oxygen extraction ratio. In hemorrhage, this association had a sharp deflection point below which a further decrease in intramucosal pH occurred concomitantly with an unchanged gut oxygen extraction ratio. Increased extraction ratio was not sufficient, not even initially, to maintain aerobic metabolism (i.e., unchanged intramucosal pH).

Animals↗

Gut intramucosal pH and intraluminal PO2 in a porcine model of peritonitis or haemorrhage.

The tonometric method of detecting decreased gut intramucosal pH (pHi) is based on the fact that carbon dioxide can diffuse through the wall of the silastic balloon of the tonometer. By using deoxified saline and measuring PO2 as well as PCO2 this study aimed to follow changes in mucosal PO2 and relate them to changes in pHi in peritonitis versus haemorrhage. Twenty five pigs were used. Five were controls, in 10 peritonitis was induced by the instillation of faeces in the abdominal cavity, and 10 were bled, half of them stepwise during three hours, and half of them rapidly down to a mean (SEM) arterial pressure of 30 (10) mm Hg. The drop in pHi correlated well with decreasing intraluminal PO2 (r = 0.63 (0.13)) in haemorrhage. In peritonitis this drop occurred within a very limited change in intraluminal PO2 (r = 0.06 (0.17)). Thus oxygen seemed to be present in the mucosa at the same time as there were signs of anaerobic metabolism as evidenced by a low intramucosal pH. Impaired oxygen extraction or utilisation, or both, is proposed as an explanation to this seemingly paradoxical situation.

Animals↗

Subcutaneous and gut tissue perfusion and oxygenation changes as related to oxygen transport in experimental peritonitis.

Peritonitis and septic shock may lead to tissue hypoxia, but this risk is not identical in all organ systems. This study was undertaken to measure changes in tissue oxygenation and perfusion in the gut wall and subcutaneous tissue, respectively, and to examine their relation to oxygen delivery and consumption. Twelve pigs were anesthesized and mechanically ventilated. An ultrasonic flow probe was placed around the superior mesenteric artery for registration of blood flow. A mesenteric vein was cannulated for blood sampling. For calculation of gut intramural pH (pHi), a Silastic balloon (Tonomitor) was placed in the lumen of the midileum. pHi was calculated from tonometrically measured PCO2 and arterial bicarbonate concentration. The subcutaneous PO2 was measured by means of an oxygen-permeable Silastic tube implanted in the subcutis of the abdominal wall. Oxygen delivery (DO2) and consumption (VO2) were determined for the gut as well as for the whole body. In six randomly allocated animals, peritonitis was induced after a stabilization period of at least 1 hr, by instillation of autologous faeces into the abdominal cavity, while the other six animals served as controls. The animals were then followed for 5 hr. pHi remained stable in the control group, whereas a drop from 7.37 to 7.02 took place in the peritonitis group. In the test group, subcutaneous oxygen tension (PscO2) already began to fall 1 hr after the induction of peritonitis, and gained the minimum at the end of the study. In peritonitis, a moderate correlation was seen between pHi and DO2 (r = 0.51 +/- 0.16); no statistical difference was noted if pHi was correlated to gut DO2 (r = 0.56 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Primary Roux-Y gastrojejunostomy versus gastroduodenostomy after antrectomy and selective vagotomy.

One hundred twenty-one patients with prepyloric ulcer disease entered a randomized clinical trial comparing gastroduodenostomy with Roux-Y gastrojejunostomy after antrectomy and selective gastric vagotomy. The postoperative course and morbidity were quite similar in the two study groups, as was the postoperative infectious complication rate. Forty-four of the patients with a Billroth I reconstruction and 52 of those with a Roux-Y reconstruction were followed up with a clinical assessment at least 6 months after the operation. The postgastrectomy symptoms were quite frequent, but did not differ between the two study groups. Seventy-five percent of the patients with a Billroth I gastroduodenostomy had symptoms corresponding to Visick grades 1 and 2, compared with 81% of those with Roux-Y reconstruction. Although the latter procedure was very effective in preventing bile reflux to the gastric remnant, no difference was observed in the gastric emptying rate after the two operations.

Adult↗

Haemodynamic characterization of the isolated (denervated) parabiotically perfused rat jejunum.

The isolated (denervated) parabiotically perfused rat jejunum was characterized for base-line haemodynamics, autoregulation of blood flow and oxygen consumption and long-term (3 h) stability with respect to both haemodynamics and the absence of tissue injury. In short-term experiments, the parabiotically perfused preparation autoregulated oxygen consumption but not blood flow over a wide range of perfusion pressures (25-85 mmHg). When the intestinal segment was subjected to near total ischaemia for I h, followed by I h of reperfusion, mucosal injury was induced which could be prevented by i.v. administration of superoxide dismutase after ischaemia just prior to reperfusion, or allopurinol prior to ischaemia. These findings support the concept of post-ischaemic reperfusion injury in the denervated preparation without hepatic ischaemia. This preparation could thus serve as an improved model for the study of the pathophysiology of post-ischaemic reperfusion injury in the rat intestine.

Animals↗

Protection of the small intestine from nonocclusive mesenteric ischemic injury due to cardiogenic shock.

In a pericardial tamponade model of cardiogenic shock in pigs, we had previously shown that acute reductions in cardiac output produce severe mesenteric ischemia due to disproportionate splanchnic vasoconstriction. In this study, we extended the period of cardiogenic shock in order to investigate the pathogenesis of ischemic injury to the small intestinal wall. Four hours of tamponade produced sustained changes in splanchnic hemodynamics, similar to those observed in the prior short-term experiments. The resultant mesenteric ischemia caused necrotic lesions of the small intestine which were characteristic of those seen in nonocclusive mesenteric ischemia in human subjects. Prior alpha-adrenergic blockade failed to prevent either sustained mesenteric vasospasm or ischemic injury. In contrast, prior blockade of the renin-angiotensin axis, whether by nephrectomy or angiotensin-converting enzyme inhibition, blocked the splanchnic vasoconstriction, and thereby protected the small intestine from ischemic injury. The primary hemodynamic and pathologic features of this model of nonocclusive mesenteric ischemia appear to be mediated by the renin-angiotensin axis.

Animals↗

The fundamental hemodynamic mechanism underlying gastric "stress ulceration" in cardiogenic shock.

Acute hemorrhagic ulceration of the gastric mucosa is seen frequently in patients with hypovolemic or cardiogenic shock. Although such lesions clearly are related to regional gastric ischemia, little attention has been directed at the underlying mechanism(s) mediating the ischemia itself. To this end, anesthetized pigs were subjected to sustained cardiogenic shock (mild hemorrhage and pericardial tamponade) such that cardiac output was reduced to 38 +/- 1% of the baseline level for 4 hours, followed by release of the tamponade, reinfusion of the shed blood, and resuscitation for 2 hours. During the period of shock, there was profound regional gastric ischemia, resulting from severe and disproportionate gastric vasoconstriction. "Blinded" gross and microscopic evaluation of the stomachs removed after the experiment revealed severe mucosal ischemic necrosis, hemorrhage, and ulceration, whereas sham-operated pigs showed no lesions. The characteristics of this model therefore mimic the essential features of the gastric "stress ulceration" syndrome. Prior confirmed total alpha-adrenergic blockade with phenoxybenzamine failed to alter these features significantly. In contrast, prior ablation of the renin-angiotensin axis, whether by angiotensin-converting enzyme inhibition with teprotide or by bilateral nephrectomy, significantly and substantially ameliorated the ischemia, vasospasm, and mucosal injury. In this model of cardiogenic shock, acute gastric mucosal "stress ulceration" is caused by a disproportionately severe regional gastric ischemia resulting from selective splanchnic vasospasm that is unaffected by sympathetic blockade but abolished by prior ablation of the renin-angiotensin axis. Like nonocclusive small bowel ischemia, ischemic colitis, and the "shock liver" syndrome, gastric "stress ulceration" is yet another component of the multiple splanchnic organ failure syndrome that appears to be mediated primarily by the remarkable sensitivity of the splanchnic vascular bed to the renin-angiotensin axis.

Animals↗