Biomedical subjects

E Kivilaakso

Publications and source records attributed to E Kivilaakso.

At least 19 recordsLinked to original sources

PubMed1999

Renal cell carcinomas and pancreatic adenocarcinomas produce nidogen in vitro and in vivo.

The production of nidogen by four renal cell carcinoma (RCC) and three pancreatic adenocarcinoma (PAc) cell lines has been studied in cell culture and in xenografted tumours in nude mice. In RCC cells, immunoreactivity for nidogen was seen only after exposure to monensin to induce cytoplasmic accumulation of secretory proteins. In PAc cells, immunoreaction was also detectable in control cells. Immunoblotting of control and monensin-exposed cells and immunoprecipitation of culture media of radioactively labelled cells demonstrated the production of nidogen polypeptide of Mr ca. 150000 by six of the seven cell lines. Basement membranes (BMs) and stroma of the xenografted tumours derived from these six cell lines demonstrated immunoreactivity for both human and mouse nidogen, as revealed with species-specific antibodies. The ability of the cells to produce nidogen in vitro and deposit in vivo was positively correlated with high histological grade of the xenografted tumours, although the small number of cell lines studied calls for further studies to confirm this. The distribution of nidogen in human RCC and PAc specimens was also studied by immunohistochemistry. There was strong immunoreactivity for nidogen in tumour stroma, BM of carcinoma cell nests, and endothelial basal lamina, but no conclusions could be drawn regarding histological grade and immunostaining patterns, because stromal production could not be ruled out. The results show that nidogen is produced by human carcinoma cells both in vitro and in vivo.

Adenocarcinoma↗

PubMed1999

Concomitant gastrin and ERBB2 gene amplifications at 17q12-q21 in the intestinal type of gastric cancer.

Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12-q21 region is very common in the intestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)-specific and ERBB2-specific probes on ten specimens of gastric carcinoma that, by using comparative genomic hybridization, showed 1) DNA copy number gain or amplification at 17q12-q21, a region known to harbor the GAS and ERBB2 genes (four cases); 2) gain of the entire chromosome 17 (three cases); or 3) normal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric cancer cell lines with or without gain at 17q12-q21 as well as a breast cancer cell line with ERBB2 amplification. Our results showed that simultaneous amplification of both GAS and ERBB2 was four- to ninefold in the tumors with the 17q12-q21 amplification. Both genes were amplified in the same nuclei, and the hybridization signals were localized to the same region of the nucleus. Overexpression of GAS and ERBB2 was observed by Western immunoblotting only in the gastric cancer cell line with gain at 17q12-q21. The ERBB2 amplification is also a recurrent change in breast cancer. To investigate whether the GAS amplification is unique in gastric cancer, fluorescence in situ hybridization analysis was performed on 40 breast cancer cell lines. The ERBB2 amplification was observed in 11 cell lines, but none of the lines showed the GAS amplification. This indicates that the formation of an amplicon, in which both the GAS and the ERBB2 genes are amplified, might be unique in gastric cancer, especially in its intestinal type, and that simultaneous amplification of both genes is important to the tumorigenesis of intestinal gastric cancer. We demonstrate here for the first time that a gene of a physiological hormone is amplified in tumors that originate from cells that normally secrete the hormone.

Breast Neoplasms↗

PubMed1999

Bactericidal/permeability-increasing protein and group I and II phospholipase A2 during the induction phase of human acute pancreatitis.

Activated endogenous mediators of inflammation have important roles in the pathogenesis and complications of acute pancreatitis (AP). These mediators include bactericidal/ permeability-increasing protein (BPI) and phospholipase A2 (PLA2). The time course of their activation during human AP is not known. The aim of this study was to evaluate the kinetics of BPI, group I (pancreatic) and group II (synovial type) PLA2 during human AP with temporally defined onset, as being induced by endoscopic retrograde cholangiopancreatography (ERCP). Serum samples of 273 consecutive patients undergoing ERCP were collected before and at 3, 6, and 24 h after ERCP. Twenty-four (8.7%) patients developed ERCP-induced pancreatitis. Seven of them were graded to have a severe disease. Forty randomly selected patients undergoing ERCP without evidence of pancreatitis served as controls. The serum concentrations of BPI and groups I and II PLA2 were measured by specific immunoassays. The mean concentration of BPI increased from 14 to 26 microg/L at 24 h after ERCP in patients with AP. In the control group, BPI values remained unchanged, and the difference was statistically significant (p<0.001). The increase of BPI was seen in 22 of 28 patients with AP at 3 h after the onset of the disease. BPI values were higher in severe post-ERCP pancreatitis than in mild disease (p = 0.07; NS). The serum concentrations of group II PLA2 before ERCP were consistently higher in the control patients than in the patients with pancreatitis, 65.8 and 14.2 microg/L, respectively. High baseline values in the control group were associated with preexisting infectious diseases. Thereafter, the mean concentration decreased in the control group to 44 microg/L and increased in the pancreatitis group up to 27.5 microg/L. The difference was statistically significant (p = 0.007). Increased group II PLA2 values were seen in 10 of 17 patients with mild AP and in five of seven patients with severe disease. There were no significant differences in group I or II PLA2 values in patients with mild or severe AP. The serum concentration of group I PLA2 increased in the patients with post-ERCP pancreatitis from 5.4 to 37.5 microg/L at 24 h. The difference was statistically significant, (p< 0.001) as compared with controls. In conclusion, in acute pancreatitis, the increase of BPI in serum starts at 3 h after the onset of the disease, and the concentration seems to correlate with the severity of the disease. Increased group II PLA2 concentrations also were seen in patients with mild AP. The kinetics of group I PLA2 resembles that of other pancreatic enzymes.

Acute Disease↗

PubMed1999

Extracellular phospholipases A2 in relation to systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis.

The pathophysiology of severe acute pancreatitis (AP) resembles other conditions with systemic inflammatory response syndrome (SIRS) such as sepsis predisposing to remote organ failure. Because extracellular phospholipases A2 (PLA2) have been implicated in AP, their serum concentrations were analyzed with respect to SIRS and systemic complications in patients with severe AP. The serum samples were collected daily for 12 days in 57 patients with severe AP. SIRS, early organ complications, local complications, and outcome of AP were recorded. Time-resolved fluoroimmunoassays were used for group I and group II PLA2 measurements. Thirty-nine (68.4%) patients fulfilled the criteria of SIRS within 12 days from admission. Pancreatic necrosis was detected in 43 (75.4%) patients. Infected necrosis was found preoperatively or at operation in five (8.8%) patients. Twenty-six (45.6%) and eight (14.0%) patients had respiratory or renal failure, respectively. Seven (12.3%) patients died of their disease. All patients with systemic complications fulfilled the criteria of SIRS. The increasing number of positive SIRS criteria was associated with increased frequency of systemic complications. Pancreatic necrosis was not significantly associated with SIRS. The serum concentration of group II PLA2 was significantly higher in patients with SIRS (p < 0.05) compared with patients without from day 7 onward. The concentration of group II PLA2 increased (p < 0.01) in patients with SIRS but decreased in patients without. The serum concentration of group II PLA2 did not differ significantly with respect to systemic complications. The concentration of group I PLA2 decreased (p < 0.05) similarly in patients with and without SIRS or systemic complications during follow-up, respectively. Early systemic complications of severe AP are associated with SIRS with increasing frequency as the number of positive SIRS criteria increases. Group II PLA2 but not group I PLA2 may have pathophysiologic importance in severe AP-associated SIRS. Increasing serum concentration of group II PLA2 seems to reflect the ongoing systemic inflammation in severe AP-associated SIRS.

Acute Disease↗

PubMed1998

Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for elective cholecystectomy, but controversy persists over use of this approach in the treatment of acute cholecystitis. We undertook a randomised comparison of the safety and outcome of LC and open cholecystectomy (OC) in patients with acute cholecystitis. METHODS: 63 of 68 consecutive patients who met criteria for acute cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The primary endpoints were hospital mortality and morbidity, length of hospital stay, and length of sick leave from work. Analysis was by intention to treat. Suspected bile-duct stones were investigated by preoperative endoscopic retrograde cholangiography (LC group) or intraoperative cholangiography (OC group). FINDINGS: The two randomised groups were similar in demographic, physical, and clinical characteristics. 48% of the patients in the OC group and 59% in the LC group were older than 60 years. 13 patients in each group had gangrene or empyema, and one in each group had perforation of the gallbladder causing diffuse peritonitis. Five (16%) patients in the LC group required conversion to OC, in most because severe inflammation distorted the anatomy of Calot's triangle. There were no deaths or bile-duct lesions in either group, but the postoperative complication rate was significantly (p=0.0048) higher in the OC than in the LC group: seven (23%) patients had major and six (19%) minor complications after OC, whereas only one (3%) minor complication occurred after LC. The postoperative hospital stay was significantly shorter in the LC than the OC group (median 4 [IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7). INTERPRETATION: Even though LC for acute and gangrenous cholecystitis is technically demanding, in experienced hands it is safe and effective. It does not increase the mortality rate, and the morbidity rate seems to be even lower than that in OC. However, a moderately high conversion rate must be accepted.

Acute Disease↗

PubMed1998

Presence of high-level DNA copy number gains in gastric carcinoma and severely dysplastic adenomas but not in moderately dysplastic adenomas.

Our aim was to investigate the presence of DNA copy number changes in gastric adenomas and to identify the changes that may play a role in gastric carcinogenesis. DNA copy number changes in 16 patients with gastric adenoma and in 22 tumors from patients with intestinal type gastric carcinomas were studied by using comparative genomic hybridization. DNA copy number changes were found in 44% of the adenoma cases and in 86% of the intestinal type gastric carcinomas. On average, gains were more common than losses (0.9 vs. 0.5 in adenomas and 4.1 vs. 1.8 in carcinomas). In adenomas, the most common gains involved chromosome 8 in 3 cases, and gain of chromosome 7 and 20q was detected in 2 cases. The most frequent losses were observed at 5q (three times). Only adenomas with severe dysplasia showed high-level amplifications that were detected at chromosome 13, 17cen-q22, and 20q12-ter. In gastric cancer, the most common gains were detected at 20q (55%), 17q12-q21 (41%), and 8q (41%), and the most common losses were detected at 18q (41%) and 4q (32%). High-level amplifications were observed at 20q (3 tumors), 17cen-q21 (3 tumors), 2p (1 tumor), and 18q (1 tumor). These findings suggest that the progression of dysplasia is associated with higher levels of DNA copy number increase (e.g., the gains at 17q and 20q), which were typically observed in the intestinal type gastric cancer. Furthermore, the results support the hypothesis that adenoma precedes cancer.

Adenocarcinoma↗

PubMed1998

Nerve terminals containing neuropeptides decrease in number after massive proximal small bowel resection in the piglet.

The aim of this study was to evaluate possible changes in the neuropeptide innervation pattern of the remaining porcine ileum following 75% proximal resection of the small intestine. Three-month-old piglets were operated on and two months postoperatively full-thickness specimens of the proximal part of the distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-, enkephalin-, substance P-, and somatostatin-containing nerve fibers were estimated in sections processed for immunofluorescence microscopy and subjected to quantitative scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular muscle layer and villi were also quantitated by computer-assisted morphometry. The number and intensity of VIP-immunoreactive fibers in the mucosa and circular muscle layer markedly decreased after resection as compared to 3-month-old and 5-month-old controls (P < 0.05). The galanin immunoreactivity index decreased significantly after resection in the circular muscle layer as compared to both control groups (P < 0.05). The increase in the number of enkephalin-immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was inhibited by the resection. We were not able to see any differences in somatostatin or substance P immunoreactivity between the groups. The results suggest that massive resection induces significant changes in the neuropeptide-containing innervation of the remaining small intestine. These findings are compatible with altered motor activity and mucosa function in the remain intestine.

Adaptation, Physiological↗

PubMed1998

Induction of proliferation in isolated guinea pig gastric epithelium during restitution after superficial injury.

Immediate repair of the gastrointestinal epithelium after superficial injury is called restitution. It is based on the migration of the surviving mucoid neck cells over the area of injury. The involvement of growth factors in the process has been recently documented. They are known to enhance the process (ie, EGF, FGF, TGF-beta) and to activate the basolateral Na+-H+-antiport (EGF). They may exert their effect by activating intracellular tyrosine kinases or by inducing chemotaxis. Yet, their precise mechanism of action in the process is unknown. The aim of the present study was to investigate the effect of modulation of the signal transduction pathway on the occurrence of proliferative mucoid neck and foveolar cells in guinea pig gastric epithelium. Therefore guinea pig gastric epithelium was mounted in Ussing chambers in vitro and perfused 4 hr after superficial injury with 1.25 M NaCl. The potential difference over the epithelium and tissue resistance were recorded simultaneously. The tissue was exposed either to cycloheximide, genistein, or to 4-phorbol myristate 13-acetate (PMA) during the 4-hr recovery, and the expression of proliferative cells was assessed by staining the tissue for proliferative cells (Ki-67). The mean proliferative index of tissues subjected to NaCl injury was significantly higher than that of uninjured control tissues after 4 hr of restitution. Inhibition of the signaling pathway with genistein decreased the proliferative index significantly, while its stimulation with phorbol myristate increased it. Both electrophysiologic and morphologic restitution were sensitive to genistein, but not to PMA or cycloheximide. Superficial epithelial injury results in a significantly increased occurrence of proliferative cells in isolated guinea pig gastric epithelium. This endogenous activation of the tissue is sensitive to inhibition by tyrosine kinases and to stimulation by protein kinases. Electrophysiologic and morphologic recovery are also affected by the modulation of the signaling pathway. This suggests that it is involved in the immediate repair process.

Animals↗

PubMed1998

Laparoscopic Nissen fundoplication: a prospective analysis of 200 consecutive patients.

Nissen fundoplication is now the most common antireflux operation for gastroesophageal reflux disease. This study is a report on the laparoscopically performed floppy Nissen procedure. Two hundred consecutive patients were analyzed (84 women, 116 men, mean age 49 years, mean duration of symptoms 5 years) after laparoscopic Nissen fundoplication between 1992 and 1996. The main indications for surgery were daily heartburn, retrosternal pain, and regurgitation demanding continuous medical therapy. Eight patients (4%) had esophageal stricture, and 21 (11%) had Barrett's esophagus with intestinal metaplasia. All patients underwent upper gastrointestinal endoscopy, 24-h esophageal pH monitoring, and esophageal manometry before and 3 months after the operation. In addition, a questionnaire was completed an average of 2.2 years (range 1.0-4.6) after the operation. The results of the study were as follows: mortality was zero, and the morbidity rate was 5%. The mean hospital stay was 3.8 +/- 2.8 days, and sick leave was 14.3 +/- 10.4 days. Postoperatively, esophagitis was healed or significantly improved in all but 4 patients (98%), and 24-h pH and lower esophageal sphincter pressure were normal. After 2 years, 87% of the patients had Visick scores of I-II. It is concluded that laparoscopic floppy Nissen fundoplication provides an efficient and safe alternative for surgical treatment of gastroesophageal reflux disease.

Adult↗

PubMed1997

17q12-21 amplicon, a novel recurrent genetic change in intestinal type of gastric carcinoma: a comparative genomic hybridization study.

We studied DNA copy number changes in gastric cancer (GC) using comparative genomic hybridization (CGH) analysis on 35 resected gastric carcinomas (22 of the intestinal type and 13 of the diffuse type). Eighty-three percent of the cases showed DNA copy number changes. Gains were more common than losses (median of 3 and 1 in primary tumors of the intestinal and diffuse type, respectively). The most common gains were detected on 20q [46%; 12 intestinal type (55%) and four diffuse type (31%)], 8q [37%; 10 intestinal type (45%) and three diffuse type (23%)], and 17q12-21 [29%; all but one intestinal type (41%)]. The most frequent losses were detected on 18q [26%; all intestinal type (41%)] and on 4q [23%; all intestinal type (32%)]. High-level amplifications were observed in the intestinal type of tumors at 17q12-21 (three tumors), 20q (three tumors). 2q (one tumor), and 18q (one tumor). In the diffuse type, high-level amplification was detected once at 13q.

Adult↗

PubMed1997

Luminal acid increases apical cell membrane resistance in isolated Necturus antral mucosa.

BACKGROUND & AIMS: The gastric mucosa must have efficient protective mechanisms to maintain physiological intracellular pH. The aim of this study was to investigate the effect of low luminal pH on apical membrane permeability. METHODS: Chambered Necturus antral mucosa was perfused with Ringer's/95% O2-5% CO2 at pH 7.25. The mucosal side was exposed to pH 4.0-2.0 with four microelectrodes placed in surface cells. Two-dimensional cable analysis was used to measure apical, basolateral, and shunt resistances. In some experiments, liquid sensor pH or Na(+)-selective microelectrodes were used. RESULTS: Luminal acidification hyperpolarized apical cell membrane potential and increased apical cell membrane resistance from 21.3 +/- 2.6 (pH 7.25) to 38.0 +/- 2.3 k omega.cm2 (pH 3.0; n = 8). The increase in apical cell membrane resistance was preceded by transient intracellular acidosis from 7.32 +/- 0.07 (pH 4.0) to 7.23 +/- 0.06 (pH 3.0; n = 6). Similar intracellular acidosis (provoked by NH4+ prepulse) failed to cause the effects observed with luminal acid. The increase in apical cell membrane resistance caused by luminal acid was eliminated when N-methyl-D-glucamine+, but not Na+, was substituted for all cations in the luminal solution. CONCLUSIONS: Luminal acidification (pH 3.0-2.0) closes apical amiloride-blockable Na+ channels. Protons are probably able to pass and even block these channels, but their effect in closing the channels does not occur intracellularly.

Acids↗

PubMed1997

Increased serum trypsinogen 2 and trypsin 2-alpha 1 antitrypsin complex values identify endoscopic retrograde cholangiopancreatography induced pancreatitis with high accuracy.

AIMS: To evaluate the clinical utility of two new tests for serum trypsinogen 2 and trypsin 2-alpha 1 antitrypsin complex (trypsin 2-AAT) in diagnosing and assessing the severity of acute pancreatitis (AP) induced by endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS: Three hundred and eight consecutive patients undergoing ERCP at Helsinki University Central Hospital in 1994 and 1995. METHODS: Patients were followed prospectively for pancreatitis and clinical outcome. They were tested for serum trypsinogen 2, trypsin 2-AAT, and amylase in samples obtained before and one, six, and 24 hours after ERCP. RESULTS: Pancreatitis developed in 31 patients (10%). Their median serum trypsinogen 2 increased 26-fold to 1401 micrograms/l at six hours after the procedure and trypsin 2-AAT showed an 11-fold increase to 88 micrograms/l at 24 hours. The increase in both markers was stronger in severe than in mild pancreatitis, and in patients without pancreatitis there was no significant increase. Baseline trypsinogen 2 and trypsin 2-AAT concentrations were elevated in 29% and 32% of patients, respectively. The diagnostic accuracy of a threefold elevation over the baseline value was therefore analysed. The sensitivity and specificity of these parameters in the diagnosis of post-ERCP pancreatitis was 93% and 91%, respectively, for serum trypsinogen 2 at six hours after the examination, and 93% and 90%, for trypsin 2-AAT at 24 hours. CONCLUSIONS: Serum trypsinogen 2 and trypsin 2-AAT reflect pancreatic injury after ERCP. High concentrations are associated with severe pancreatic damage. The delayed increase in trypsin 2-AAT compared with trypsinogen 2 appears to reflect the pathophysiology of AP. A greater than threefold increase in trypsinogen 2 six hours after ERCP is an accurate indicator of pancreatitis.

Acute Disease↗

PubMed1997

Poor prognosis of gallbladder cancer persists regardless of improved diagnostic methods. Incidence and results of surgery during 20 years in Helsinki.

BACKGROUND AND AIMS: The ominous prognosis of primary gallbladder cancer is well-known. This study assesses whether the prognosis has improved, and whether the substantial development in the radiologic imaging techniques is reflected in the survival of these patients. MATERIAL AND METHODS: The series consisted of 122 patients operated on for primary cancer in the gallbladder in the Helsinki City area between 1970 and 1990. RESULTS: The mean age of the patients was 68.6 years and did not change during the period, but there was a significant proportional increase in male patients. Only 2% of patients had a localized disease at the time of diagnosis, and there was no improvement in the diagnostic sensitivity during the observation period. Yet, the number of unexpected postoperative cancer diagnoses increased from 4% to 15% during the two decades. The primary mortality decreased from 21% to 13%, the one-year survival increased from 7% to 13%, whereas the five-year survival remained unchanged. CONCLUSIONS: During the past two decades the frequency of surgery for primary gallbladder cancer has increased significantly among males in the Helsinki City area. Regardless of the improved immediate survival the long-term survival has remained poor. The marked development in radiologic techniques is not reflected in the prognosis of these patients. Even under conditions in which the potential for the diagnosis of a malignant gallbladder disease is available, the opportunities for radical surgery are not utilized maximally, which is a cause for concern.

Adult↗

PubMed1997

Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane.

We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta 1 and alpha 3 integrin subunits and laminin alpha 3 chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha 6 integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due to an abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha 3 beta 1 integrin receptor recognizing laminin-5.

Adenocarcinoma↗

PubMed1996

Serum complex of trypsin 2 and alpha 1 antitrypsin as diagnostic and prognostic marker of acute pancreatitis: clinical study in consecutive patients.

OBJECTIVE: To estimate the usefulness of serum concentrations of the complex of trypsin 2 and alpha 1 antitrypsin in diagnosing and assessing the severity of acute pancreatitis in comparison with serum C reactive protein, amylase, and trypsinogen 2 concentrations (reference markers). DESIGN: Markers were measured in consecutive patients admitted with acute abdominal pain that was either due to pancreatitis or to other disease unrelated to the pancreas (controls). SETTING: Department of surgery of a teaching hospital in Helsinki. SUBJECTS: 110 patients with acute pancreatitis and 66 with acute abdominal diseases of extrapancreatic origin. On the basis of the clinical course, acute pancreatitis was classified as mild (82 patients) or severe (28 patients). MAIN OUTCOME MEASURES: Clinical diagnosis of acute pancreatitis and severity of the disease. RESULTS: At admission all patients with acute pancreatitis had clearly raised concentrations of trypsin 2-alpha 1 antitrypsin complex (32 micrograms/l), whereas only three of the controls had such values. Of the markers studied, trypsin 2-alpha 1 antitrypsin complex had the largest area under the receiver operating curve, both in differentiating acute pancreatitis from extrapancreatic disease and in differentiating mild from severe disease. CONCLUSIONS: Of the markers studied, trypsin 2-alpha 1 antitrypsin complex was the most accurate in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for acute pancreatitis.

Abdominal Pain↗

PubMed1996

Urinary trypsinogen-2 test strip for acute pancreatitis.

BACKGROUND: A simple, rapid test is specific and sensitive enough to distinguish, in patients with clinically suspected acute pancreatitis, those whose abdominal pain is indeed of pancreatic origin has proved elusive. METHODS: In two consecutive series of surgical patients in a teaching hospital, whose acute abdominal pain turned out to be due to acute pancreatitis (n-57) or extrapancreatic in origin (n=40), we studied urinary trypsinogen-2 in two ways. A test strip, incorporating monoclonal antibodies to two epitopes on trypsinogen-2, recorded a blue line when concentrations exceeded 50 microgram/L; we also measured trypsinogen-2 concentrations in the laboratory. FINDINGS: In the patients with acute pancreatitis the test strip was positive in 52 and negative in five, whereas in the 40 extrapancreatic controls there were four false positives. In a further set of 57 orthopaedic controls, one urine was strip-test positive. Concentrations of urinary trypsinogen-2 and the test-strip results were in good agreement and in only three of the 154 patients were the two approaches discrepant, at the 50 microgram/L cut-off. INTERPRETATION: These findings, in patients whose acute abdominal pain was known to be pancreatic in origin or not, are encouraging but need to be confirmed in a consecutive series of patients in whom the diagnosis of pancreatitis is in doubt.

Abdominal Pain↗

PubMed1996

Early localization of necrosis by contrast-enhanced computed tomography can predict outcome in severe acute pancreatitis.

A total of 161 primary contrast-enhanced computed tomography (CT) scans of patients with acute necrotizing pancreatitis taken between 1982 and 1994 were analysed retrospectively. The aim was to assess the prognostic significance of the extent and anatomical site of pancreatic tissue necrosis in the first contrast-enhanced CT scan. The scans were obtained a mean of 2.9 days after the onset of symptoms. The pancreatic head was affected in 107 patients, the body in 119 and the tail in 138. Pancreatic tissue necrosis, when divided into four groups according to anatomical site, correlated with overall clinical outcome. The anatomical site of necrosis was clearly better than its crude extent in predicting the risk of complications. For patients with necrosis in the head of the pancreas, the outcome was as severe as when the entire pancreas was affected. In contrast, for patients with necrosis only in the distal part of the pancreas, the outcome was favourable with few complications. The exact site of pancreatic tissue necrosis should be known when early contrast-enhanced CT is used in prognostic scoring.

Acute Disease↗

PubMed1996

Role of Na(+)-H(+)-antiport in restitution of isolated guinea pig gastric epithelium after superficial injury.

In addition to its pHi regulatory function Na(+)-H(+)-antiport is also involved in volume regulation of epithelial cells, particularly in neutral conditions. It is also known that the antiport is activated after ligand binding following growth factor receptor activation. The aim of the present study was to evaluate the role of the antiport in restitution of gastric mucosa and whether its activity is dependent on the type of superficial injury. Therefore the fundic epithelium of guinea pig stomach was perfused in an Ussing chamber in neutral conditions. Na(+)-H(+)- and Cl(-)-HCO3(-)-antiports were inhibited with 1.0 mM amiloride, 1.0 mM SITS, or with HCO3- removal and Na(+)-K(+)-2Cl(2-)-cotransporter with 0.3 M furosemide during 4 hr of restitution after superficial injury induced either by 1.25 M NaCl or by 1.0% Triton. Luminal exposure of the epithelium to amiloride had no effect on restitution but serosal application abolished the process completely. The inhibitory effect of amiloride was similar after both NaCl and Triton injury. The inhibition of Cl(-)-HCO3(-)-antiport with SITS interfered with the process as well, while HCO3- removal had no significant inhibitory effect, nor did the inhibition of Na(+)-K(+)-2Cl(-)-cotransporter. The morphologic findings were in accordance with the electrophysiologic measurements in each pair of tissues. It is concluded that the Na(+)-H(+)-antiport is essential for the epithelial cells during restitution even in neutral conditions, but a functional Cl(-)-HCO3(-)-antiport is also required. The activity of Na(+)-H(+)-antiport is sensitive to basolateral amiloride and is necessary regardless of the type of chemical injury.

Amiloride↗