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M Lempinen

Publications and source records attributed to M Lempinen.

At least 19 recordsLinked to original sources

Clinical value of severity markers in acute pancreatitis.

Acute pancreatitis is a common digestive disease of which the severity may vary from mild, edematous to severe, necrotizing disease. An improved outcome in the severe form of the disease is based on early identification of disease severity and subsequent focused management of these high-risk patients. However, the ability of clinicians to predict, upon presentation, which patient will have mild or severe acute pancreatitis is not accurate. Prospective systems using clinical criteria have been used to determine severity in patients with acute pancreatitis, such as the Ranson's prognostic signs, Glasgow score, and the acute physiology and chronic health evaluation II score (APACHE II). Their application in clinical practise has been limited by the time delay of at least 48 h to judge all parameters in the former two and by being cumbersome and time-consuming in the latter. Contrast-enhanced computed tomography is presently the most accurate non-invasive single method to evaluate the severity of acute pancreatitis. It cannot, however, be performed to all patients with acute pancreatitis. Therefore, considerable interest has grown in the development of reliable biochemical markers that reflect the severity of acute pancreatitis. In this article we critically appraise current and new severity markers of acute pancreatitis in their ability to distinguish between mild and severe disease and their clinical utility.

Acute Disease↗

Urinary trypsinogen activation peptide as a marker of severe acute pancreatitis.

BACKGROUND: Trypsinogen activation peptide (TAP) may be an early marker of severe pancreatitis. Previous studies have included all patients with organ failure in the group with severe pancreatitis, although patients with transient organ failure may have a good prognosis. The aim of this study was to determine the value of urinary TAP estimation for prediction of severity of acute pancreatitis, and to validate use of several markers of prediction of severity against a new, stringent definition of severity. METHODS: Patients with acute pancreatitis were recruited within 24 h of onset of symptoms. Urine and blood samples were collected for 24 h, and Acute Physiology And Chronic Health Evaluation (APACHE) II (24 h), Ranson (48 h) and Glasgow (48 h) scores were calculated. Severe acute pancreatitis was defined by the presence of a local complication or the presence of organ failure for more than 48 h. RESULTS: Urinary TAP levels were significantly greater in patients with severe pancreatitis than in those with mild disease during the first 36 h of admission. The highest of three estimations of TAP in the first 24 h was as effective as APACHE II at 24 h in predicting severity. At 24 h after admission, urinary TAP was better than C-reactive protein (CRP) in predicting severity. The combination of TAP and CRP at 24 h allowed identification of high- and low-risk groups. The new definition of severity excluded 24 of 190 patients with transient organ failure; none of these patients died. CONCLUSION: Use of TAP improved early prediction of the severity of acute pancreatitis. Organ failure that resolves within 48 h does not signify a severe attack of acute pancreatitis.

APACHE↗

Impact of chronic and acute high-fat feeding on acute experimental pancreatitis complicated by endotoxinaemia.

BACKGROUND: Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP. METHODS: Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed. RESULTS: LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment. CONCLUSION: An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.

Animals↗

Jejunal diverticulosis: a potentially dangerous entity.

Although jejunal diverticulosis is a rare entity and usually asymptomatic, it may cause chronic symptoms and acute complications. Because of the rarity of the entity, diagnosis is often delayed, resulting in unnecessary morbidity and mortality. The purpose of this study was to draw attention to jejunal diverticula and their complications. The medical records of 8 consecutive patients with complications due to small-bowel diverticula treated at our department during the past 4 years were reviewed. All diverticula were located in the jejunum. Seven patients had acute complications, 3 patients had an intra-abdominal abscess, 2 had free perforation with diffuse peritonitis, 1 had a bowel occlusion and 1 patient had concomitant bleeding and occlusion. One patient presented with chronic symptoms. A preoperative diagnosis of jejunal diverticula, before explorative laparotomy, was not reached in any of the 7 patients with acute symptoms. In the patient with chronic symptoms, multiple jejunal diverticula complicated by a jejuno-colic fistula and foreign body were found at laparotomy. On patient died of multiorgan failure. Small-bowel diverticulosis is a rare entity, but it should not be regarded as a clinically insignificant finding. It may be difficult to make a preoperative diagnosis. Patients with incidentally detected proximal jejunal diverticula, at imaging studies or at laparotomy, warrant close observation and awareness that the diverticula may cause serious complications.

Aged↗

Sequential changes in pancreatic markers in acute pancreatitis.

BACKGROUND: Trypsinogen activation within acinar cells plays a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize temporal changes of trypsinogen-1, trypsinogen-2, complexes of trypsin-1-alpha1-antitrypsin (T1-AAT) and trypsin-2-alpha1-antitrypsin (T2-AAT), trypsinogen activation peptide (TAP) and pancreatic secretory trypsin inhibitor (PSTI) in patients with AP. METHODS: The study comprised 64 consecutive patients with AP (19 with severe disease) and 32 controls. The concentrations of trypsinogen-1 and -2, PSTI, T1-AAT and T2-AAT were determined by time-resolved immunofluorometric assays (IFMA), and TAP was measured using a competitive enzyme immunoassay from serum and urine. RESULTS: The concentrations of trypsinogen-1 and -2 in serum reflected similar patterns, but excretion of trypsinogen-1 into urine was markedly lower than that of trypsinogen-2, the concentration of which correlated strongly with disease severity. The concentrations of T1-AAT were no higher in severe AP than in mild AP, while T2-AAT concentrations were significantly higher in severe than in mild disease. PSTI increased over the course of several days, showing strong correlation with disease severity. The concentrations of plasma and urinary TAP decreased rapidly to undetectable levels. During the early phase of AP, TAP correlated with the disease severity in plasma and urine but there was no difference between controls and patients with mild AP. CONCLUSION: More pronounced changes in trypsinogen-2 and its complex with AAT than in those of trypsinogen-1 were demonstrated, suggesting that trypsinogen-2 might play a more important role in the pathogenesis of AP than earlier believed. Urinary PSTI showed features warranting further investigations as a marker of disease severity.

Acute Disease↗

Predicting the severity of acute pancreatitis by rapid measurement of trypsinogen-2 in urine.

BACKGROUND: Early identification of patients at risk of developing a severe attack of acute pancreatitis (AP) is of great importance because rapid therapeutic interventions improve outcome. At a cutoff of 50 microg/L, trypsinogen-2 measured by a rapid urinary dipstick is a sensitive and specific diagnostic test in AP. The trypsinogen-2 concentration correlates with the severity of the disease, and a test with a higher cutoff might therefore be useful for prediction of disease severity. METHODS: We increased the detection limit of the urinary trypsinogen-2 test strip (Actim Pancreatitis) from 50 microg/L to 2000 microg/L and evaluated the prognostic value of this test. The results were compared with those obtained with serum C-reactive protein and the acute physiology and chronic health evaluation II (APACHE II) score. The study population consisted of 150 consecutive patients with AP (42 with severe disease). RESULTS: The sensitivity of the rapid urinary test strip (detection limit, 2000 microg/L) for prediction of severe AP, both on admission and at 24 h, was 62%; specificities were 87% and 85%, respectively, positive predictive values were 65% and 62%, and negative predictive values were 85% and 85%. C-Reactive protein had a sensitivity of only 38% on admission, but at 24 h, it was 83%; specificities were 90% and 70%, respectively, whereas positive predictive values were 59% and 52%, and NPVs were 79% and 91%, respectively. On admission the positive-likelihood ratio for the urinary trypsinogen-2 test strip was 4.8, and at 24 h it was 4.2; for C-reactive protein, the values were 3.7 and 2.7, respectively. CONCLUSIONS: The urinary trypsinogen-2 dipstick is a simple and rapid method for prediction of severe acute pancreatitis.

Acute Disease↗

Matrix metalloproteinases 2 and 9 in indomethacin-induced rat gastric ulcer.

The restoration of functional connective tissue is a major goal of the wound healing process. The 72- and 92-kD gelatinases (MMP-2 and MMP-9) are extracellular matrix metalloproteinases (MMPs), which are known to degrade type IV and V collagens and gelatin, and have a potential role in wound healing. The spatial and temporal gelatinolytic activities of MMP-2 and MMP-9 were analyzed as a function of ulcer age, in homogenates of rat, indomethacin-induced, chronic gastric ulcers. The rats were sacrificed on 1, 3, 7, 12, 18, 24 and 28 days after subcutaneous indomethacin injections. Zymographic analyses revealed elevated activation of MMP-9 and latent and active MMP-2 in gastric ulcers, when compared to gastric tissue from non-indomethacin-treated rats. The intact tissue and tissue from ulcerous lesions contained MMP-2. The highest activity of MMP-2 was found in 3 day gastric ulcers and returned to the control level by day 24. MMP-9 was not present in the intact tissue and the highest gelatinolytic activity of MMP-9 was also observed on the 3rd day after administration of indomethacin. The activity thereafter decreased and returned to the control level by day 24. In situ hybridization was used to evaluate which cells synthesize MMP-2 and MMP-9. MMP-2 was seen mostly in fibroblast-like cells in the submucosa and MMP-9 in macrophage-like cells in the mucosa on the margins of the ulcers. Thus, we conclude that these two MMPs seem to have different functions during the gastric ulcer injury/healing process. MMP-2 may participate in the physiological turnover of the gastric extracellular matrix, whereas MMP-9 may be important in the early phase of gastric ulcer formation and also in the healing process.

Animals↗

The role of the kidney in canine blood pressure control: direct assessment of the closed-loop gain.

1. The feedback control of arterial blood pressure by the kidney in the range of hours was investigated in resting, conscious foxhounds. 2. A servo-control device (connected to an aortic occlusive cuff implanted above both renal arteries) was used to maintain a constant pressure difference of 20 mmHg between aortic pressure measured proximal (mean arterial blood pressure: MAP) and distal (renal artery pressure: RAP) to the aortic cuff. 3. Protocol 1 (n = 6) served as a 4 h time control without intervention, protocol 2 (n = 6) consisted of three periods: after a control of 20 min duration, the servo-control device was activated for 180 min; this was followed by a recovery period of 40 min. Protocol 3 (n = 6) was as protocol 2, but during converting-enzyme inhibition. 4. Servo-control increased plasma renin activity (PRA) transiently from 0.5 ng angiotensin I (AI) ml-1 h-1 to a peak value of 2.4 ng AI ml-1 h-1, subsequently both RAP and MAP rose to reach a new steady state. During this increase in RAP, PRA declined to 1.4 ng AI ml-1 h-1. 5. On average, the compensation of the pressure decrease sensed by the kidney amounted to 63% of the error signal (closed-loop gain of 0.63 +/- 0.1). 6. Converting-enzyme inhibition reduced this closed-loop gain significantly (protocol 2 vs. protocol 3, 0.63 +/- 0.1 vs. 0.15 +/- 0.1; P < 0.05). 7. It is concluded, that the kidney plays an important role in medium-term blood pressure regulation, most probably via the renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗

Pancreatic resection versus peritoneal lavage in acute necrotizing pancreatitis. A prospective randomized trial.

Twenty-one patients with acute fulminant alcoholic pancreatitis were randomly allocated to either pancreatic resection group (11 patients) or nonoperative peritoneal lavage group (10 patients). Only patients under 50 years were included in the study to minimize the role of other severe disease. These patients represented the most severe cases of acute pancreatitis at our Department, constituting only 2% of all patients with acute pancreatitis during this period. The diagnosis was based on clinical symptoms and on signs indicating severely impaired systemic organ functions. All patients underwent contrast-enhanced computed tomography (CT), which showed contrast enhancement below 30 Hounsfield units. In the operated cases, the diagnosis of necrotizing pancreatitis was verified histologically. All patients with conservative treatment had dark brown fluid at peritoneal puncture. There was a difference (nonsignificant) in mortality (3/11 and 1/10, respectively), complication rate, or in the need of reoperations between the groups. Nonoperative peritoneal lavage was followed with shorter treatment at the intensive care unit (16.2 versus 25.9 days, respectively). The hospital stay also was significantly shorter in the nonoperative group (44.3 versus 56.1 days). The results indicate that intensive conservative treatment is justified as an initial therapy even in the most severe cases of acute pancreatitis.

Acute Disease↗

Roux-en-Y reconstruction for severe postoperative duodenogastric reflux disease.

Thirty-two patients underwent Roux-en-Y diversion because of symptomatic postoperative duodenogastric reflux. Operative mortality was nil, but eight patients had transiently delayed gastric emptying postoperatively. At follow-up 45 months (range 9-89 months) after the Roux-en-Y operation 28 (88%) patients were in good clinical state; four patients were classified as poor. The main cause for a poor clinical outcome was a stomal ulcer in three patients. Atrophic gastritis was seen in the operative specimens of 22 patients. Severity of gastritis evaluated by gastroscopic biopsies at follow-up was less marked in 16 patients as compared to the histology of the samples from the original operation (P less than 0.001). Intestinal metaplasia had regressed in nine cases and proceeded in three cases (NS). Severe postoperative duodenogastric reflux can be treated by the Roux-en-Y reconstruction with good subjective relief of symptoms and beneficial histologic changes in the gastric stump mucosa.

Adult↗

Pseudocysts in chronic pancreatitis. Surgical results in 102 consecutive patients.

Preoperative symptoms, diagnoses, and postoperative outcomes in 102 consecutive patients with pancreatic pseudocysts were analyzed. Upper epigastric pain, loss of weight, obstructive jaundice, and sudden arterial bleeding from the pseudocyst were the most common preoperative symptoms. Ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography were the most useful diagnostic tools in the evaluation of the presence, size, location, and possible pancreatic ductal communications of the pseudocyst. In a single thick-walled pseudocyst, the best long-term results were achieved by internal drainage. Pancreatic resection is justified if the patient already has diabetes or multiple pseudocysts or if the pseudocyst is not amenable to internal drainage. The most fatal preoperative complication was a sudden arterial bleeding from a pseudocyst. In treating this complication, hemostasis with transcystic arterial ligation and external drainage of the pseudocyst gave the best results.

Adult↗

Surgical treatment of gastric carcinoma.

To investigate changes in the results of treatment of gastric carcinoma, two 10-year periods between 1963 and 1982 with 641 and 630 patients, respectively, were compared. In the two groups, 94 percent and 92 percent of patients were operated on. The operation was considered curative in 200 and 265 patients in Groups 1 and 2, respectively. There was a shift towards more radical operations, with 215 total or subtotal gastrectomies in Group 2 compared with 76 in Group 1, when distal gastric resection was considered radical enough. Despite the increasing number of curative operations and more radical surgery in Group 2, no progress in the 5-year survival rate was noted. Distal and subtotal gastrectomies gave slightly better results than total gastrectomies, but the most important single factor contributing to the long-term survival was cancerous invasion of the serosa. It is concluded that in the past 20 years, the results of surgical treatment of gastric carcinoma have not improved, despite the more advanced diagnostic methods and more radical surgery.

Aged↗

Microangiography and dynamic computed tomography in experimental chronic pancreatitis in the pig.

Chronic pancreatitis was induced in 22 piglets by dividing all pancreatic attachments to the duodenum. Ten piglets served as controls. The animals were subjected to dynamic computed tomography (CT) two, four or six weeks after operation. Microangiography was also performed on the pancreas two, four or six weeks after operation, following dynamic computed tomography. Microangiography revealed significant changes in the vasculature in advanced chronic pancreatitis. The arteries and arterioles were fewer than normal, their walls were thickened and their diameters exhibited variation. The capillary network was loose and the capillaries were not as well filled as in healthy animals. Contrast enhancement of the pancreas was, however, similar in all experimental animals to that in the healthy controls. It was concluded that the morphological changes seen in chronic pancreatitis histologically and on microangiography could not adversely affect contrast-enhanced CT because there were no changes in the function of the capillary network. On the basis of these results, dynamic CT should give no more information than CT with intravenous contrast medium in chronic pancreatitis.

Angiography↗

Treatment of pancreatic fistulas with somatostatin and total parenteral nutrition.

Nineteen pancreatic fistulas were treated with somatostatin (ST) and total parenteral nutrition (TPN). Five of the fistulas developed in an uninflamed pancreas, whereas 14 fistulas developed secondary to a necrotizing or chronic pancreatitis. Fistular output varied between 20 and 800 ml/day (median, 160 ml) during TPN before ST treatment; amylase concentration was 10,500-800,000 UI/l. Twelve of 16 (75%) fistulas were contaminated with bacteria. Thirteen of 19 (68%) fistulas closed after a median treatment of 7 (range, 2-14) days. Seven of eight fistulas with open drainage to the bowel healed, whereas only one of six with obstructed drainage closed. All of the uninfected fistulas and half of the infected fistulas closed. The findings suggest that somatostatin treatment speeds up the closure of pancreatic fistulas with open drainage to the bowel but is not beneficial when the intestinal drainage of the fistular region to the bowel is obstructed.

Adult↗

Growth of human colorectal carcinoma implants in the mouse subrenal capsule assay.

The subrenal capsule assay (SRCA) in normal immunocompetent mice was performed from 1331 implants of 43 human colorectal carcinomas to evaluate the possible applications for clinical chemosensitivity testing. Also the effect of an immunosuppressive agent, cyclosporine, was tested on the growth of tumours. Histologically in all except one of 23 saline-treated tumours the original tumour tissue was replaced by granulation tissue and inflammatory cells. This was also true in cyclosporine-treated mice since in only one of the nine tests tumour cells were observed. The macroscopic growth of the implants in the cyclosporine-treated mice was significantly less than in the saline-treated mice. Flow cytometric DNA-analysis revealed that the difference between macroscopic growth of saline and cyclosporine-treated groups was observed only in DNA-diploid tumours. We conclude that new methods are required to preserve the viability of human colorectal carcinoma in the SRCA.

Animals↗

Pancreatic trauma: acute and late manifestations.

A retrospective analysis of 47 patients with pancreatic trauma is presented. A total of 43 patients presented with acute pancreatic injury, 32 after blunt abdominal trauma. Isolated blunt pancreatic injuries were a considerable diagnostic problem with a mean delay from trauma to operation of 9.4 days. At operation peripancreatic drainage in mild injuries and distal resection in cases of ductal injury were the commonest procedures. The overall mortality was 19 per cent, but only three of the eight deaths were attributable to the pancreatic injury. The overall complication rate was 63 per cent and the pancreatic complication rate was 33 per cent. Four patients presented with chronic pancreatitis resulting from previously untreated blunt abdominal trauma 0.5-21 years earlier. Clinically, they did not differ from the manifestations of chronic pancreatitis of other aetiological origins.

Abdominal Injuries↗