NO treatment in a patient with severe right-to-left shunt due to an intrapulmonary av-fistula.
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Adult↗
Biomedical subjects
W Uhl
Publications and source records attributed to W Uhl.
Human pancreas-specific protein. A diagnostic and prognostic marker in acute pancreatitis and pancreas transplantation.
CONCLUSION: Human pancreas-specific protein (hPASP) is a very sensitive reflector of the extent of pancreatic necrosis on the cellular level, and is of both diagnostic and prognostic value in acute pancreatitis. Furthermore, it allows the estimation of the severity of graft pancreatitis soon after simultaneous renal and pancreatic transplantation. BACKGROUND: Diagnosis of acute pancreatitis (AP) has been improved in the past 15 yr as new methods for the determination of specific pancreatic enzymes have been developed. However, these enzymes have no prognostic implications. In this prospective study, we evaluated the role of human pancreas-specific protein (hPASP) in comparison with pancreatic amylase and C-reactive protein (CRP) in acute pancreatitis and pancreas transplantation. PATIENTS AND METHODS: The study included 40 patients (22 female, 18 male; mean age 51 yr, range 22-88 yr) with AP and 7 patients (2 female, 5 male; mean age 37 yr, range 25-49 yr) with type I diabetes and renal insufficiency who underwent simultaneous kidney and pancreas transplantation. By means of contrast-enhanced computed tomography (CT) and/or intraoperative findings, patients were judged to have edematous-interstitial (AIP, n = 20, mean age 55.2 yr, range 24-88 yr) or necrotizing pancreatitis (NP, n = 20, mean age 46.3 yr, range 22-81 yr). Serum hPASP concentration was measured daily by a commercial radioimmunoassay technique. In 25 healthy subjects and in several control groups (35 patients with chronic pancreatitis, 20 patients with pancreatic carcinoma and 80 patients with different gastrointestinal diseases) a single blood specimen was taken at hospital admission for the determination of the normal range of hPASP and for specificity analysis. RESULTS: The upper normal value for hPASP in healthy subjects was found to be 52 ng/mL. Serum hPASP was elevated in all patients suffering from AP, with a median of 343 ng/mL (lower-upper quartile: 192-478 ng/mL) at hospital admission. In the daily serum monitoring with respect to the onset of symptoms, significantly higher hPASP levels were found in NP compared with AIP after day 2 (p < 0.001). In patients with NP, peak values of hPASP correlated significantly with the extent of pancreatic necroses measured by contrast-enhanced CT-scanning, whereas CRP did not. Six patients of the transplantation group had the same serum hPASP course as AIP, with almost normal values on the third postoperative day. One patient had elevated levels throughout the observation period. This patient suffered from necrotizing graft pancreatitis, confirmed by relaparotomy, and died because of subsequent septic complications.
Acute Disease↗
Influence of etiology on the course and outcome of acute pancreatitis.
It has been supposed that there are differences with regard to clinical course and outcome due to the underlying etiological factor in acute pancreatitis. Therefore, the objective of this study was to analyze the severity of the disease, serum enzymes, indicators of necrosis, systemic complications, and mortality in acute pancreatitis with regard to the etiology. One hundred ninety patients with acute pancreatitis (127 male, 63 female) were studied prospectively and subdivided into three etiological groups: (i) alcohol, (ii) gallstones, and (iii) other causes and idiopathic acute pancreatitis. Severity scores (Ranson and Bank) and findings by contrast-enhanced computed tomography were similar in all three groups. Analysis of serum enzymes [lipase, aspartate aminotransferase (ASAT)] and indicators of necrosis (C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, and lactate dehydrogenase) showed only for ASAT within 24 h significantly higher levels in biliary acute pancreatitis in comparison with the other groups. There were no differences in the rate of infected pancreatic necrosis and mortality in alcohol-related acute pancreatitis (31 and 5.3%), biliary acute pancreatitis (38 and 10%) and acute pancreatitis due to other etiological factors (43 and 5.5%). In conclusion, this study clearly showed that once the pathogenetic mechanisms have initiated the disease, the course and outcome of acute pancreatitis are not influenced by the underlying etiological factor.
Acute Disease↗
Hyperlipaemia intensifies the course of acute oedematous and acute necrotising pancreatitis in the rat.
BACKGROUND: Serum triglyceride concentrations higher than 10 to 20 mmol/l are probably a risk factor for developing acute pancreatitis in humans. AIMS: To therefore analyse the influence of hyperlipaemia on the course of acute oedematous and acute necrotising pancreatitis in rats. SUBJECTS: Male Wistar rats were used in all experiments. METHODS: Six different groups of animals were used: two groups without pancreatitis (controls), two with acute oedematous pancreatitis, and two with acute necrotising pancreatitis. One group from each pair was treated with Triton WR 1339, which induces endogenous hyperlipaemia. Blood samples were taken from all subjects to measure triglyceride, cholesterol, amylase, and lipase. Pancreatic tissue samples were taken and the degree of pancreatic damage was judged microscopically. RESULTS: In the control groups no significant changes occurred, either in serum enzyme activities or in histology. The hyperlipaemic subgroup of animals with acute oedematous pancreatitis developed significantly higher (p < 0.001) serum amylase activities and a greater degree of histological damage (p < 0.01) than the animals of the non-hyperlipaemic acute oedematous pancreatitis group. In the animals with necrotising pancreatitis, serum lipase activity and the histological degree of pancreatic damage were significantly higher in the hyperlipaemic animals than in the non-hyperlipaemic animals. CONCLUSION: This study shows that hyperlipaemia intensifies the course of acute oedematous and acute necrotising pancreatitis in rats.
Acute Disease↗
Protease-antiprotease interactions and the rationale for therapeutic protease inhibitors.
A number of pancreatic enzymes have been suggested as the initiating factor for acute pancreatitis. In particular, the relationship between proteases and antiproteases has been examined extensively, based on the suspicion that an imbalance between them is the central factor in the pathogenesis of acute pancreatitis. Animal studies with antiproteolytic agents in models of acute pancreatitis have shown an improvement in outcome. However, more recently, prospective, randomized, multicentre trials treating human acute pancreatitis with antiproteolytic drugs (aprotinin, gabexate mesilate, and even fresh frozen plasma) have failed to show any benefit in the clinical setting. Thus, clinically, it seems likely that antiproteolytic therapy has no effect on the course of severe acute pancreatitis. Today, the mortality in severe acute pancreatitis is determined by septic complications due to infected pancreatic necroses in the late phase 2-3 weeks after the onset of the disease. Death in the early phase of the disease has become increasingly rare where an imbalance between proteases and antiproteases may be involved.
Acute Disease↗
[Technique and outcome of surgical therapy 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 necroses indicating parameters in the serum, like CRP and PMN-elastase are 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 of disease should be treated in the intensive-care unit. Patients with biliary acute pancreatitis should be examined by ERCP with the performance of a papillotomy with stone removal in case of impacted ampullary stones within 24 hours. Surgical decision-making in patients with necrotizing pancreatitis should be based on the development of septic signs due to infected pancreatic necrosis. The information about infected pancreatic necrosis can be easily obtained by a bedside ultrasound-guided fine needle aspiration and bacteriological examination of the aspirate [gram stain plus culture]. Patients without organ complications and with focal necroses should be treated conservatively while patients with persisting organ insufficiencies or progressive multiple organ failure despite maximum intensive care measures 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. For this postoperative therapeutical concept three comparable procedures are available today, the closed continuous lavage, the 'open packing technique' and the management by planned, staged re-laparotomies. Hospital mortality in severe acute pancreatitis has been reduced to less than 15% by these procedures in experienced hands.
Acute Disease↗
[Increased phospholipase A2 and diacylglycerol lipase activities in colorectal carcinoma: possibility for carcinoma prevention or therapy?].
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Aged↗
[Inhibition of secretion in pancreas surgery reduces postoperative complication rate: a meta analysis of 4 multicenter studies].
We report on a meta-analysis of four randomized, placebo-controlled, double-blind multicenter trials evaluating the role of perioperative octreotide treatment in the prevention of postoperative complications following elective pancreatic surgery. From a total of 963 patients (483 placebo, 480 octreotide), the postoperative complication rate (329 placebo, 206 octreotide) and the number of patients with postoperative complications (placebo 38%, octreotide 22%) were significantly higher in the placebo groups compared with the octreotide groups. Postoperative morality was comparable between the placebo (3.9%) and the octreotide (3.5%) groups. These data indicate that perioperative application of octreotide can prevent postoperative complications following pancreatic surgery.
Double-Blind Method↗
Lipid peroxidation and glutathione metabolism in chronic pancreatitis.
In experimental models of pancreatitis lipid peroxidation products are increased possibly because of an enhanced generation of oxygen radicals. The purpose of this study was to determine whether lipid peroxidation products are increased in pancreatic tissue and serum of patients suffering from chronic or acute pancreatitis. In 20 patients undergoing operative treatment for chronic (n = 11) and acute pancreatitis (n = 9) the levels of malondialdehyde, conjugated dienes, and reduced and oxidized glutathione were determined in resected tissue samples. The excised tissue was examined and evaluated by light microscopy. Shortly before operation the serum concentrations of malondialdehyde, alpha-amylase, and lipase were measured. Pancreatic tissue from eight organ donors who had no abdominal trauma or pancreatic disease served as control. In chronic pancreatitis, conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. In acute pancreatitis only the tissue and serum malondialdehyde levels were significantly high, whereas conjugated dienes remained within the normal range. Serum malondialdehyde levels correlated significantly with tissue concentrations (r = 0.76; p < 0.05) but not with the clinical course or the enzyme levels. In chronic pancreatitis, the increased tissue levels of lipid peroxidation products and the changes in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. In hemorrhagic necrotizing pancreatitis, however, oxygen radical-induced lipid peroxidation cannot be proven. Apparently, other pathomechanisms are involved in the development of the severe tissue damage.
Acute Disease↗
Management of sterile necrosis in instances of severe acute pancreatitis.
BACKGROUND: The clinical management of sterile pancreatic necrosis is still a matter of debate. In this study we analyzed the clinical course and outcome of patients with sterile necrotizing pancreatitis treated surgically versus nonsurgically. STUDY DESIGN: Between May 1982 and December 1993, 249 patients with necrotizing pancreatitis (NP) entered this study, of which 172 (69 percent) had intraoperatively or fine needle aspiration-proven sterile NP. One hundred seven of 172 patients underwent surgery (S group) with necrosectomy and continuous postoperative closed lavage and 65 of 172 were treated by nonsurgical means (NS group). RESULTS: Median Ranson and admission APACHE II scores were 4.7 (range, 1 to 10) and 11 (range, 1 to 29) in the S group, significantly higher than those in the NS group with 3.0 (range, 0 to 6) (p = 0.022) and 8 (range, 1 to 23) (p = 0.036). After 48 hours of intensive care treatment, APACHE II scores persisted at 10.5 (range, 1 to 29) in the S group and decreased to 6 (range, 0 to 15) (p = 0.013) in the NS patients. Median C-reactive protein (CRP) levels on admission were 179 mg/L and 68.5 mg/L (p = 0.023), respectively. Within 72 hours, 61 (94 percent) of 65 NS-managed patients responded to intensive care therapy, whereas organ complications persisted or increased and thus led to surgery in the S group. Mortality rates were 13.1 percent in the surgically treated patients and 6.2 percent in the nonsurgically treated patients (p = NS). CONCLUSIONS: Most patients with limited and sterile pancreatic necrosis respond to intensive care treatment. Indication for surgery in sterile NP should be based on persisting or advancing organ complications despite intensive care therapy. APACHE II scores and admission CRP levels represent a helpful tool in decision making for surgical or nonsurgical management of NP.
APACHE↗
The analytical and clinical performance of the new Boehringer Mannheim Enzymun-Test PSA assay for prostate-specific antigen.
A combined evaluation effort of the Boehringer Mannheim Research and Development and Evaluation Departments and the University Hospital Rotterdam is described regarding the new, fully automated Enzymun-Test PSA assay for prostate-specific antigen. The study consisted of an analytical and a clinical part. At both sites, the vast majority of intra-assay coefficients of variation ranged from 2 to 3% above prostate-specific antigen = 1 microgram/l. Below that concentration higher coefficients of variation were measured. Comparable results were obtained for the interassay imprecision. The analytical sensitivity (lower limit of detection) was found to be 0.02 microgram/l at both sites. Regarding the linearity of the assay no systematic drift to either elevated or lower values which increasing dilution was found. Deviations remained well in the range between 100 +/- 10%. The correlation with the Abbot IMx PSA assay as performed with a large set of clinical specimens revealed: y (= Enzymun) = 1.16x (= IMx) + 0.0; r = 0.985; n = 245. In this comparison study small differences between benign prostatic hyperplasia patients and prostate cancer patients were detected, perhaps partly based on the differences in recognition patterns of various molecular prostate-specific antigen forms in both assays. A follow-up after radical prostatectomy with 17 patients (50 serum samples) also showed a good comparability between the Enzymun-Test and the IMx assay. The limited check of the reference range resulted in data comparable to what can be found in the literature: out of 100 samples originating from healthy males, aged 20-60 years, 99 had prostate-specific antigen values lower than 4 micrograms/l. Based on our findings it can be concluded that the new Enzymun-Test PSA assay meets the current state-of-the-art criteria in prostate-specific antigen methodology.
Adult↗
A multicenter study of phospholipase A2 in patients in intensive care units.
BACKGROUND: Multiple organ failure (MOF) is becoming the most common cause of death in patients in surgical intensive care units. In this respect, a multicenter study in four different groups of patients in surgical intensive care units was done to evaluate the role of phospholipase A2 (PLA2) in comparison with C-reactive protein (CRP) and polymorphonuclear (PMN) elastase. STUDY DESIGN: A total of 223 patients entered the study: 73 patients with multiple injuries, 46 patients with diffuse peritonitis, 52 patients with sepsis, and 52 patients in a control group who were at a higher risk for postoperative sepsis after defined surgical interventions. The patients underwent a daily monitoring of PLA2, CRP, and PMN elastase for seven days. RESULTS: Phospholipase A2 activity remained within the normal range in patients with multiple injuries and patients in the control group, indicating that this parameter is not influenced by the postaggression metabolism. In contrast, in patients with peritonitis, high PLA2 values were found from the beginning. The efficiency for predicting a lethal MOF was 85 percent for PLA2 (cut-off 80 U/L) in patients if determined at the day of operation. A comparably favorable efficiency (84 percent) was demonstrated for PMN elastase in patients with multiple injuries (cut-off 205 micrograms/L) measured at day one. CONCLUSIONS: These efficiency rates of PLA2 in peritonitis and PMN elastase in multiple injuries were comparable or even better than multifactorial scoring systems used in the study. C-reactive protein did not contribute to an early estimation of the prognosis in all groups analyzed. Therefore, the measurement of PLA2 in patients with diffuse peritonitis and PMN elastase in patients with multiple injuries, as single parameters, is recommended to estimate the individual risk for the occurrence of lethal MOF.
Adolescent↗
Multicentre evaluation of a new fully automated enzyme immunoassay for total prostate-specific antigen.
UNLABELLED: The evaluation is reported of a newly developed automated assay for measuring total prostate-specific antigen: Enzymun-Test PSA. Starting with a small field study, the study was extended to 74 laboratories in different countries. The median values for the intra-assay imprecision ranged from 5.0% (0.0-2.0 micrograms/l) to 2.5% (> 10.0 micrograms/l). For the inter-assay imprecision the results for the same ranges were 23.2 and 3.8%, respectively. The lower limit of detection, biological and functional sensitivity were 0.03, 0.1 and 0.25 micrograms/l, respectively. The linearity and dilution experiments showed acceptable data. The determined reference ranges (95% confidence intervals) were: men < 40 years: 0.1-1.3 micrograms/l, men 40-50 years: 0.2-2.0 micrograms/l, men 50-60 years: 0.2-3.0 and men > 60 years: 0.2-4.5 micrograms/l. Comparison of Enzymun-Test PSA with most present-day commercially available assays generally revealed very good correlations. IN CONCLUSION: the new Boehringer Mannheim Enzymun-Test PSA is compatible with the state-of-the-art for the measurement of total prostate-specific antigen.
Adult↗
[Therapy of acute pancreatitis].
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Acute Disease↗
Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group.
There is increasing evidence that the hypercortisolemia in inflammatory diseases suppresses the elaboration of proinflammatory cytokines, thus protecting the host from its own defence reactions. In severe sepsis and septic shock cortisol levels are usually elevated, but some patients may have relative adrenal insufficiency. This may contribute to the overwhelming systemic inflammatory response syndrome. We evaluated the impact of low-dose hydrocortisone infusion (10 mg/h) on the course of the systemic inflammatory response syndrome. This dose corresponds to a maximum secretory rate of cortisol achieved in corticotropin-stimulated healthy humans. In a prospective observational study 57 surgical patients with severe sepsis or septic shock were studied, of which in addition to the conventional treatment 12 patients were infused with low-dose hydrocortisone, and 45 were treated without any corticosteroid. In the longitudinal analysis the systemic inflammatory response--as judged by body temperature, cardiovascular response, and kinetics of inflammatory mediators such as phospholipase A2, C-reactive protein, and neutrophil elastase--started to differ in favor of the hydrocortisone-treated patients after 2 days of treatment (P < 0.05, Mann-Whitney U test). The difference disappeared after withdrawal of exogenous cortisol. Shock reversal was achieved in all patients treated with low-dose hydrocortisone. The data provide evidence that low-dose hydrocortisone infusion attenuates the systemic inflammatory response in human septic shock. From an immunological point of view a relative cortisol deficiency may contribute to the amplified immune response in systemic inflammatory diseases. A randomized clinical trial must clarify the impact of low-dose hydrocortisone infusion on the clinical course and outcome of septic shock patients.
Adrenal Insufficiency↗
Octreotide in the treatment of acute pancreatitis: results of a unicenter prospective trial with three different octreotide dosages.
Acute necrotizing pancreatitis is still associated with high morbidity and mortality. In this prospective clinical trial, we analyzed the effect of octreotide in patients with acute pancreatitis. Eight patients received either 3 x 100, 3 x 200 or 3 x 500 micrograms octreotide subcutaneously per day over a period of 10 days. The complication rate was lower in the group of patients who received 3 x 200 or 3 x 500 micrograms octreotide than in the control group and the group of patients who received the dosis of 3 x 100 micrograms octreotide per day. The results of this study are promising and must be validated in a controlled clinical trial with octreotide in a larger patient population.
Acute Disease↗
Prophylaxis of complications after pancreatic surgery: results of a multicenter trial in Germany.
Major pancreatic resection still carries a considerable risk for morbidity and even mortality. Complications occurring after pancreatic surgery are chiefly linked with exocrine pancreatic secretion. Therefore to inhibit exocrine pancreatic secretion perioperatively seems to be a promising concept in the prevention of complications following pancreatic resection. The hormone somatostatin and its synthetic analogue octreotide have been demonstrated to inhibit exocrine pancreatic secretion profoundly, particularly the secretion of proteases is decreased. In a randomized placebo-controlled multicentric and double-blind trial we analyzed the role of octreotide in the prevention of post-operative complications after major pancreatic surgery. A significant reduction of complications (fistula, abscess, fluid collection, sepsis, pulmonary insufficiency, postoperative acute pancreatitis) could be demonstrated in patients receiving octreotide (3 x 100 micrograms/day s.c.). The effect of octreotide was particularly true in patients undergoing a Whipple resection for cancer.
Austria↗
Free fatty acids in serum of patients with acute necrotizing or edematous pancreatitis.
Serum concentrations of free fatty acids (FFA) were assayed in 20 patients with acute necrotizing pancreatitis (ANP). Pancreatic and peripancreatic fat necrosis was verified on operation and/or by contrast-enhanced computed tomography. For comparison, 20 patients with acute edematous pancreatitis (AEP) were examined. On admission, FFA serum levels were 1.14 +/- 0.12 (SEM) mmol/L in ANP and, thus, significantly (p < 0.03) higher than in AEP (0.78 +/- 0.09 mmol/L). The two groups also differed in the later course: in ANP, the FFA values remained raised (d 5-11:0.86 +/- 0.13 mmol/L; p > 0.05 vs day 1), whereas in AEP, the FFA concentrations normalized within 1 wk (d 2-4:0.52 +/- 0.11 mmol/L; d 5-11:0.39 +/- 0.05 mmol/L; p < 0.05 vs day 1 and p < 0.01 vs ANP). Serum FFA correlated positively with C-reactive protein levels (rs = 0.42; p < 0.01), but has less discriminating potency between ANP and AEP. In AEP, the initial peak may correspond to the disease outburst itself and to unspecific stress. In ANP, the higher and sustained elevation of FFA may predominantly mirror the ongoing pancreatic parenchymal and extrapancreatic fat necrosis, and be pathophysiologically relevant, especially in view of significantly reduced serum albumin levels in ANP.
Acute Disease↗