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W Uhl

Publications and source records attributed to W Uhl.

At least 109 records · Page 6Linked to original sources

Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group.

BACKGROUND: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. METHODS: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. RESULTS: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placebo and gabexate mesilate groups. CONCLUSIONS: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

Acute Disease↗

Complications of acute pancreatitis and their management.

Severe acute pancreatitis remains a disease with high hospital mortality. In the period from 1991 to 1992, several articles dealt with the complicated form of acute pancreatitis. There is no question that necrosis of the pancreas and fatty tissue in the peripancreatic spaces and particularly secondary infection of necrosis are the most important prognostic factors for these patients. Indications for surgery and the efficacy of conservative treatment of acute pancreatitis (including interventional measures) have not been clearly determined. Most surgeons would elect to operate on a patient with multiorgan failure caused by infected necrosis, however. Another major question is the type of surgery to be performed: closed continuous lavage of the lesser sac and retroperitoneal cavities, staged relaparotomy, or open packing. This review concentrates on articles pertaining to complicated acute pancreatitis in humans.

Acute Disease↗

Surgical strategies in acute pancreatitis.

The most important diagnostic step in the management of patients with acute pancreatitis is to discriminate between interstitial-edematous and necrotizing pancreatitis. Measurement of C-reactive protein or PMN-elastase is useful in detecting the necrotizing course of acute pancreatitis. While patients with acute edematous pancreatitis can be treated on a regular ward, patients with a necrotizing course should be treated in the ICU. Surgical decision-making in necrotizing pancreatitis should be based on the extent of necroses found by contrast-enhanced CT, and on the development of septic signs due to bacterial infection of the necroses. Information about the latter can be obtained by a bedside ultrasound-guided fine needle aspiration and bacteriological examination of the aspirate. Patients with no organic complications and with focal necrosis should be treated conservatively, while patients with persistent organic insufficiencies or progressive multiple organ failure despite maximum intensive care are candidates for surgical therapy. The procedure of choice in necrotizing pancreatitis is the careful removal of necrotic tissue (necrosectomy) followed and supplemented by a postoperative regimen for the continuous evacuation of further necrotic debris. Hospital mortality rate has been reduced to less than 20% by this procedure.

Abscess↗

Pancreatic necrosis: an early finding in severe acute pancreatitis.

Despite the clinical importance of pancreatic necrosis in the course of acute pancreatitis, little is known about when it develops. Serum C-reactive protein (CRP) is a reliable parameter with a high deduction rate for pancreatic necrosis. We analyzed 199 patients with acute pancreatitis. The development of pancreatic necrosis was ascertained by a daily measurement of serum CRP in 45 patients with contrast-enhanced computed tomographic-proven necrotizing pancreatitis. In all 45 cases, the criteria for pancreatic necrosis were satisfied within the first 4 days of the onset of symptoms. This indicates that pancreatic necrosis is an early finding that develops within hours.

Acute Disease↗

Clinical relevance of experimental acute pancreatitis.

There are several well-standardized models of experimental acute pancreatitis such as the closed duodenal loop technique, cholecystokinin or cerulein stimulation, duct injection and diet-induced acute experimental pancreatitis. With regard to human acute pancreatitis, experimental models in animals have a considerable high clinical relevance if the subject of investigation concerns pathogenetic, morphological and diagnostic approaches to the disease; as regards the treatment modalities and causative therapy of acute pancreatitis, experimental models in animals up to now seem to be far away from the clinical situation and therefore these protocols have low clinical relevance. The reasons for this discrepancy are outlined in this paper.

Acute Disease↗

Acute pancreatitis: when and how to operate.

Patients with proved necrotizing pancreatitis should be treated in an intensive care unit. Surgical management of necrotizing pancreatitis is indicated if an acute abdomen or persistent or increasing signs of organ complications develop, such as pulmonary or renal insufficiency, cardiocirculatory dysfunction or metabolic disorders, and these do not respond to maximum intensive care treatment over at least 72 h. Besides these so-called non-responders to ICU treatment, operative management is clearly indicated in patients who develop signs of sepsis on the basis of a bacteriologically positive fine-needle aspiration of pancreatic necroses. In patients with minor necroses without any bacterial contamination and without extensive retroperitoneal fatty tissue necroses intensive care therapy can be successful without the necessity of a surgical intervention. The gold standard of surgical management of necrotizing pancreatitis is careful removal of necrotic tissue, drainage of bacterially infected area, elimination of the pancreatogenic ascites in order to prevent systemic spread of vasoactive and toxic substances and interruption of the inflammatory process. For the treatment of pancreatic necrosis we strongly support surgical debridement (necrosectomy), supplemented by postoperative closed continuous lavage of the lesser sac and the adjacent necrotic cavities. In 152 patients suffering from severe necrotizing pancreatitis the hospital mortality was 12.5% (19/152) by this surgical approach.

Acute Disease↗

Characterization of two phospholipases A2 in serum of patients with sepsis and acute pancreatitis.

Pancreatic phospholipase A2 and non-pancreatic ascitic phospholipases A2 were studied in sera of healthy individuals and of patients suffering from sepsis or acute pancreatitis. In gel filtration experiments, immunoreactive ascitic phospholipase A2, as determined in serum by a time-resolved fluoroimmunoassay, eluted either unassociated with an apparent M(r) of 10,000-14,000 or associated with proteins of high molecular mass. Catalytically active ascitic phospholipase A2 was associated with high molecular weight proteins. In acute pancreatitis the catalytically active and immunoreactive pancreatic phospholipase A2 eluted mainly as a protein of M(r) of 14,000. The results of the gel filtration experiments indicate that pancreatic phospholipase A2 is not associated with other proteins in human serum, whereas ascitic phospholipase A2 is associated with protein(s) of relative high molecular weight, or exists in different polymeric forms. We also purified phospholipase A2 from sera of healthy individuals by ion exchange chromatography and HPLC. The enzyme was homogenous, displayed an M(r) of approximately 13,500 as judged by SDS-polyacrylamide gel electrophoresis, and reacted with an antibody raised against ascitic phospholipase A2.

Acute Disease↗

Determination of pancreatic lipase by immunoactivation technology. A rapid test system with high sensitivity and specificity.

This paper describes the test characteristics and clinical relevance of a newly developed homogeneous enzyme immunoassay IMAC lipase test for the determination of serum pancreatic lipase. The method of determination is based on an immunoactivation technology and utilizes antibody fragments against human pancreatic lipase covalently bound to the marker enzyme horseradish peroxidase. The serum samples of 408 persons were investigated with this new assay. The within-run and day-to-day precision, the linearity, and the recovery of this immunoassay correspond to a very high degree to the requirements made of a modern immunological test. Comparison with an ELISA method resulted in a correlation coefficient of 0.971, whereby the IMAC lipase assay tended to register lower serum values. The serum range for the IMAC lipase test is 0-47 micrograms/L, based on a normal collective of 187 healthy controls. A sensitivity of 95.8% for the diagnosis of acute pancreatitis at a cutoff level of twice the upper normal range and a specificity of 99.3% at an efficiency of 99.8% can be given. The advantage of the IMAC lipase test method is its ability to be adapted to work on automatic laboratory analyzers.

Acute Disease↗

Antineutrophil cytoplasmic autoantibodies (ANCA) in acute pancreatitis.

Antineutrophil cytoplasmic autoantibodies, which are now considered reliable serological markers of acute necrotizing vasculitic diseases, were measured in 11 patients with acute necrotizing pancreatitis and 12 patients with acute interstitial pancreatitis. When tested by indirect immunofluorescence, none of the sera was positive for diffuse cytoplasmic staining, and none was positive for perinuclear staining of antineutrophil cytoplasmic antibodies. Also by the sensitive enzyme-linked immunosorbent assay, none of the sera was positive when purified alpha-granule fraction of granulocytes was used as an antigen. We can therefore conclude that neither the diffuse cytoplasm-reacting, nor the perinuclear form of antineutrophil cytoplasmic antibodies, is involved in cases of acute pancreatitis.

Acute Disease↗

[Surgical therapy of acute pancreatitis].

In patients with proven acute pancreatitis which is not necrotizing conservative therapy leads to a rapid pain release; after sanitation of the basic disease, complete healing is achieved. In case of a biliary pancreatitis with incarcerated gallstones in the papilla an EPT with removal of the choledochal stones is carried out within the first 12 hours after onset of incarceration symptoms; after disappearance of the symptoms of acute pancreatitis an endoscopic or minilap.-cholecystectomy is performed. Conservative therapy leads to a complete cure in patients with minor necroses without any bacterial contamination and without extensive retroperitoneal fatty tissue necroses. Surgery is indicated if a surgical acute abdomen or a sepsis develops, if patients do not respond to maximum intensive care treatment over at least 72 hours, or if organ complications, such as pulmonary/renal insufficiency, cardiocirculatory dysfunction/shock and metabolic disorders grow worse under ICU treatment. The choice procedure against bacterially contaminated necrosis is their careful removal by necrosectomy or débridement. Resectional techniques should be avoided. A third of patients needs reoperation because of extensive inflammatory processes in the retroperitoneum and around the pancreas. Treatment centres report a hospital mortality rate of clearly below 20%.

Acute Disease↗

PMN-elastase in comparison with CRP, antiproteases, and LDH as indicators of necrosis in human acute pancreatitis.

We analyzed the role of polymorphonuclear granulocytes (PMN)-elastase in predicting the prognosis of patients with acute pancreatitis in comparison with C-reactive protein (CRP), lactate dehydrogenase (LDH), and the two antiproteases alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-M). Fifty-two patients with acute pancreatitis were subdivided according to morphological criteria into 29 patients with edematous pancreatitis and 23 patients with necrotizing pancreatitis. Within 5 days after the onset of acute pancreatitis, the accuracy rates for detecting necrotizing pancreatitis were 86%, 84%, 82%, 72%, and 69%, using cutoff levels of 120 mg/L for CRP, 120 micrograms/L for PMN-elastase, 270 U/L for LDH, 1.5 g/L for alpha 2-M, and 3.5 g/L for alpha 1-AT, respectively. The median peak value of PMN-elastase was reached on day 1 of acute pancreatitis in contrast to the median peak of CRP, which was at its highest between days 3 and 4. PMN-elastase represents a reliable indicator, comparable with CRP, for the staging of acute pancreatitis. The advantage of PMN-elastase over CRP appears to be its earlier increase and the greater dynamism of its serum course. Finally, the results suggest that CT scanning for the evaluation of the extent of intra- and extrapancreatic necrosis could be restricted to those patients with increased values of PMN-elastase and CRP.

Acute Disease↗

Carboxylic ester hydrolase. A sensitive serum marker and indicator of severity of acute pancreatitis.

When using clinical criteria, both falsely positive and falsely negative diagnoses of acute pancreatitis (AP) are often made. Based on a clinical study, elevated serum levels of the pancreatic lipolytic enzyme carboxylic ester hydrolase (CEH) was recently suggested to be a highly specific marker of acute pancreatitis. To determine the sensitivity of the test for AP, a study on patients with the diagnosis set objectively was necessary. In the present study, AP was diagnosed by contrast-enhanced computed tomography in 64 patients, and histopathological examination of tissue removed at laparotomy in 18 of them. By these criteria, 42 patients suffered from acute interstitial pancreatitis (AIP), and 22 patients from necrotizing pancreatitis (NP). Based on the CEH concentrations in the first serum sample obtained in each patient, the sensitivity of CEH for pancreatitis was 98%. From the second day after admission, CEH levels in patients with NP were significantly higher than in patients with AIP. Furthermore, in patients with NP, CEH values remained at a raised level for the following 10 d, whereas a significant decrease of CEH values was noted in patients with AIP. In contrast, total serum amylase activities were higher in patients suffering of AIP than in patients suffering of NP during the observation period. We conclude, that the sensitivity of the CEH test is very high for AP. CEH concentrations remaining at a high level are suggestive of NP, whereas diminishing CEH levels are suggestive of AIP.

Acute Disease↗

Serum phospholipase A2 in patients with multiple injuries.

Catalytic phospholipase A2 activity (CA-PLA2) and the concentration of immunoreactive pancreatic PLA2 (IR-PLA2) were measured in serum samples from 12 patients with multiple injuries (median Injury Severity Score: 41). CA-PLA2 was increased in all patients and positive correlations were found between the extent of the increase of CA-PLA2, mortality, and impairment of pulmonary function. IR-PLA2 values were slightly increased in the serum of nine patients with multiple injuries. Of these nine patients, eight had an additional blunt abdominal trauma. On the other hand, no relationship was found between IR-PLA2 and CA-PLA2 values. This finding was confirmed by immunoadsorption experiments with an antiserum to human pancreatic PLA2, which demonstrated that the increased serum levels of IR-PLA2 were not responsible for the increased CA-PLA2 values. The results suggest the existence of at least two immunologically different phospholipase A2 enzymes in sera of patients with multiple injuries.

Adolescent↗

Duodenum-preserving resection of the head of the pancreas--an alternative to Whipple's procedure in chronic pancreatitis.

Duodenum-preserving resection of the head of the pancreas is a low-risk operation for patients with chronic pancreatitis. Subtotal resection of the head of the pancreas does not result in a significant diminishment in the exocrine and endocrine functions of the pancreas. Owing to the limited nature of the intervention, hospital and late mortality rates are low. More than 80% of the patients with CP have experienced long-lasting relief of pain after this procedure. In comparison with the Whipple operation duodenum-preserving resection of the head of the pancreas spares the patient a gastrectomy, a duodenectomy, and resection of the extrahepatic bile duct.

Anastomosis, Surgical↗

Diagnostic value of immunoreactive phospholipase A2 in acute pancreatitis.

In a prospective clinical trial 85 patients with acute pancreatitis were analysed for serum total amylase, pancreatic amylase, pancreatic lipase, trypsin, elastase 1, and immunoreactive phospholipase A2 (IR-PLA2). The diagnostic sensitivity of serum IR-PLA2 was comparable to that of serum total amylase, pancreatic amylase, and trypsin. The specificity of IR-PLA2 is superior to that of serum total amylase determination due to the fact that the IR-PLA2 determination is based on an antibody against human pancreatic PLA2.

Acute Disease↗