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W Uhl

Publications and source records attributed to W Uhl.

At least 73 records · Page 4Linked to original sources
PubMed1998

Phospholipase A2 isoforms are altered in chronic pancreatitis.

OBJECTIVE: To determine if phospholipase A2 (PLA2) type II and type IV mRNA expression and protein are altered in chronic pancreatitis. SUMMARY BACKGROUND DATA: PLA2s have an important regulatory function in several signaling pathways, especially in inflammation. In this study, we examined the expression of three PLA2 isoforms (type I, type II, and type IV) in chronic pancreatitis. METHODS: The distribution of PLA2 was studied in 15 pancreas samples obtained from patients with chronic pancreatitis using immunohistochemical, Northern blot, and in situ hybridization techniques. Normal pancreas obtained from healthy organ donors served as control. RESULTS: Northern blot analysis revealed enhanced mRNA levels of PLA2 type II (5.7-fold) and type IV (5.1-fold) in chronic pancreatitis (p < 0.01) versus normal pancreas. In normal pancreas, intense PLA2 type I immunostaining was present in acinar cells, whereas PLA2 type II immunostaining was visible only in some acinar cells. In chronic pancreatitis, PLA2 type II immunostaining was present more frequently and with higher intensity in acinar cells. Furthermore, PLA2 type II immunoreactivity was more abundant in metaplastic ductal cells in the chronic pancreatitis samples. By in situ hybridization, areas with ductal metaplasia in chronic pancreatitis exhibited intense PLA2 type IV mRNA signals. All chronic pancreatitis tissues with concomitantly increased mRNA expression for PLA2 type II and type IV exhibited a higher degree of degeneration, ductal metaplasia, and fibrosis. CONCLUSIONS: Upregulation of PLA2 types II and IV in areas with more histologic damage suggests that these PLA2 isoforms might contribute to the morphologic changes that occur in chronic pancreatitis.

Adult↗
PubMed1998

The clinical value of human pancreas-specific protein procarboxypeptidase B as an indicator of necrosis in acute pancreatitis: comparison to CRP and LDH.

Early assessment of severity in acute pancreatitis (AP) has a major impact on further treatment. Previous studies have shown that human pancreas-specific protein (hPASP)/procarboxypeptidase B (PCPB) is a new diagnostic and prognostic marker in AP. In the present study we focused on the prognostic properties of this parameter and analyzed the clinical value of hPASP in discriminating edematous from necrotizing AP. The results were compared to those for C-reactive protein (CRP) and lactate dehydrogenase (LDH). A total of 70 patients was enrolled in this prospective study. Based on contrast-enhanced computed tomography or intraoperative results, 39 patients (27 male, 12 female; median age, 42 years; median Ranson score, 6) suffered from necrotizing pancreatitis (NP) and 31 patients (12 male, 19 female; median age, 57; median Ranson score, 1.5) from acute interstitial-edematous pancreatitis (AIP). Serum concentrations of hPASP/PCPB, CRP, and LDH were measured at 24-h intervals over 14 days after admission by a radioimmunoassay (upper normal value, 60 ng/ ml), a lasernephelometric assay (upper normal value, 4 mg/L), and an enzymekinetic method (upper normal value, 240 U/L), respectively. During the overall observation period concentrations of hPASP/PCPB, CRP, and LDH were significantly higher in patients with NP compared to those with AIP. Based on receiver operating characteristics, the best cutoff levels for predicting NP were >200 ng/ml for hPASP/PCPB, >140 mg/L for CRP, and >290 U/L for LDH. Discrimination between AIP and NP was best on day 3 for both hPASP/PCPB (sensitivity, 91%; specificity, 64%; accuracy, 79%) and CRP (sensitivity, 83%; specificity, 84%; accuracy, 83%) and on day 5 of AP for LDH (sensitivity, 88%; specificity, 100%; accuracy, 91%). The overall accuracy in differentiating AIP from NP within the first 4 days after onset of symptoms was 74% for hPASP/PCPB, 75% for CRP, and 76% for LDH. None of the parameters correlated with the extent of necrosis or the etiology of AP. hPASP/PCPB provides good discrimination between AIP and NP at an early stage of the disease, with results comparable to those for CRP and LDH. Although hPASP/PCPB is both disease specific and predictive for necrosis, the clinical use of this test in its present form is limited due to drawbacks in terms of test performance and cost factors.

Adolescent↗
PubMed1998

[Surgical therapy of ileus of the small intestine].

BACKGROUND AND AIMS: Small bowel obstruction is a disease the surgeon frequently is confronted with. In the present study the records of the patients (n = 202) with mechanical obstruction of the small intestine from the last four years were analysed and the results are critically compared with the literature. METHODS: In the reported retrospective study the length of patient's history, the cause of bowel obstruction, the preoperative examinations performed, the kind of surgical intervention and the postoperative management and outcome were investigated. RESULTS: The average patient's age was 62 years, the mean preoperative duration of symptoms was 6.5 days. 77% of the patients had underwent abdominal surgery prior to the obstruction. Conventional x-ray was performed in 92%, gastrographin passage in 46% and CT-scan in 23% of the cases. The average length of hospitalisation was 12 days. The overall postoperative morbidity was 21%, the mortality 2.5%. CONCLUSION: It could be shown that patient's history, clinical symptoms and conventional x-rays of the abdomen are sufficient for the indication of surgical intervention. In uncertain cases the examination of the passage with contrast medium is recommended. The surgical results of small bowel obstruction management have significantly improved over the past decades, today's mortality is lower than 5%.

Aged↗
PubMed1998

[Surgical therapy of ileus of the large intestine].

Acute colonic obstruction is a life threatening emergency. In this prospective study 69 patients suffering from large bowel obstruction, admitted between November 1993 and March 1998 to the University hospital of Bern, were analyzed with regard of the performed surgical procedure. The causes of obstruction were colorectal carcinomas (38%), other malignancies (19%), volvulus (13%), hernias (10%), diverticulitis (7%) and others (13%), 8 benign and 19 malignant lesions were surgically treated without colonic resection, the latter by colostomy (13), ileostomy (5) or bypass (1). All the other 42 patients had their obstruction resected within 24 hours after admission, 24 of them with primary anastomosis and 18 as a two-staged procedure. However, 9/18 (50%) patients never have had restoration of bowel continuity. No three-stage procedure was planned or performed. In-hospital mortality was 4/69 (5.8%), all of them after staged resections due to non-surgical complications. No anastomotic leakage was clinically apparent, neither in one-stage procedures, nor in completed two-stage procedures. Median length of total hospital stay in one-stage and two-stage procedures was 14 and 30 days, respectively. The advantages of one-stage procedures, especially in terms of subtotal colectomy, are discussed on the basis of an overview of the literature.

Acute Disease↗
PubMed1998

[A new pathophysiologic concept in chronic pancreatitis: tissue destruction induced via inflammatory mediators].

In the present study we analyzed the three phospholipase A2 isoforms phospholipase A2 type I (PLA2-I), phospholipase A2 type II (PLA2-II), phospholipase A2 type IV (PLA2-IV) in chronic pancreatitis in comparison with normal pancreas. PLA2-I also named pancreatic phospholipase is a digestive enzyme while PLA2-II and PLA2-IV play an important function in inflammatory reactions. In chronic pancreatitis PLA2-I mRNA expression was significantly reduced. In contrast, PLA2-II and PLA2-IV mRNA were increased in 73% of the chronic pancreatitis samples (PLA2-II; 5.7-fold overexpressed; PLA2-IV:5.1-fold overexpressed; p < 0.05). By in situ hybridization the highest expression signals were found in chronic pancreatitis samples in areas with ductal metaplasia. Immunohistochemistry of PLA2-II revealed also the strongest immunoreactivity in ductal metaplasia. Increased PLA2-II and PLA2-IV mRNA levels were associated with a higher degree of tissue destruction, ductal metaplasia and degree of fibrosis. Our findings indicate that PLA2-II and PLA2-IV seems to play a role in the pathobiological alterations in chronic pancreatitis and contribute to the morphological changes which occur in chronic pancreatitis.

Adult↗
PubMed1998

Infections complicating pancreatitis: diagnosing, treating, preventing.

The most important risk factor in patients suffering from acute necrotizing pancreatitis is pancreatic infection, a factor that determines the course of the disease, its therapeutic management, and its outcome. The bacterial infection route is very likely via the colon. In patients with acute pancreatitis, the infection rate is about 40 to 70% within the first 3 wks. Bacteria most frequently found are those from the gastrointestinal tract: Escherichia coli, Pseudomonas species, Streptococcus fecalis, Enterococcus, and Staphylococcus aureus. Screening methods for infected necrotizing pancreatitis include fine needle puncture by ultrasonography or computed tomographic guidance with Gram staining and culture of the aspirate. We previously investigated different broad-spectrum antibiotics with regard to their efficacy at preventing infection. This analysis indicated that antibiotics have different efficacy factors based on pharmacodynamic properties. Imipenem and quinolones, in combination with metronidazole, are the drugs of choice for treating or preventing pancreatic infection, whereas aminoglycosides do not enter the pancreas and therefore are not indicated. Based on increasing evidence that patients with acute necrotizing pancreatitis will benefit by early and appropriate antibiotic therapy, we altered the approach in such patients with an immediate start of antibiotic therapy continued for at least 14 days. We have found a reduction of the infection rate to 33% (11/32) in the third week after the onset of the disease. This treatment of the infection and the possibility of delaying operative intervention resulted in optimal surgical conditions. However, further prospective, controlled, and randomized studies are necessary to determine which antibiotics and antimycotic therapeutic regimens should be chosen.

Anti-Bacterial Agents↗
PubMed1998

Elecsys CEA, PSA and AFP. Clinical results of a multicentre evaluation.

Three tumormarker assays, Elecsys CEA, PSA and AFP, have been evaluated in an international multicentre study to characterize their clinical performance and to verify the comparability with the corresponding tests of the Enzymun-Test product line and other methods. For each of the markers results were obtained from four laboratories. On the basis of 314 and 199 specimens respectively, (preliminary) reference ranges could be established for CEA and PSA. For the prostate marker, the age dependence of the antigen level could be clearly confirmed. Mean concentrations range between 0.51 ng/ml (< 40 years) and 3.57 ng/ml (> 70 years). Referring to CEA, 95th percentiles of 4.31 ng/ml and 2.69 ng/ml were elaborated for smokers and nonsmokers. In general, good to excellent correlations (r > 0.98) were found between the Elecsys and Enzymun-Tests. Regarding the systematic comparability of both systems, most of the slopes derived from the individual method comparison studies are within the +/- 10% range of the respective standardization results. The specific distribution pattern of the individual tumormarker values elaborated with sample material of known clinical background, reflects the well established categorization of different benign and malignant diseases according to their characteristic marker levels. Of utmost importance, however, is the excellent comparability of the Elecsys assays with the corresponding Enzymun-Tests and the FDA approved AIA 1200 tests from TOSOH in follow-up studies. Almost superimposable concentration curves guarantee that identical diagnostic information is derived from all three methods. Especially for PSA, a series of measurements on sera of prostatectomized patients proved the usability and clinical value of the test also for this particular indication. For either one of the Elecsys tests, the feasibility of using plasma as sample material was verified.

Adult↗
PubMed1998

[Definition of predictors of a complicated course in acute pancreatitis].

It is of utmost importance to assess the severity of acute pancreatitis immediately in order to identify patients with severe or necrotising disease who can benefit from early intensive care therapy. Additionally, in face of new therapeutic concepts (e.g., antibiotic therapy) and for the evaluation of new drugs (e.g. PAF antagonist) patients should be staged as soon as possible into mild and severe disease. At hospital admission it is not possible to assess the severity on a clinical basis. The "gold standard" up to now has been imaging procedures (contrast-enhanced CT and MRI) which should be preserved for the severe cases to estimate the extent of pancreatic necrosis. The ideal predictor in blood/urine should be objective, reliable, cheap, easy to measure, and available every time and should have on hospital admission a high efficacy and independence from other diseases. As single factors there are a variety of mediators of the "systemic inflammatory response syndrome" which are elevated in this disease (C-reactive protein, antiproteases, enzyme activation peptides, PMN-elastase, complement factors, interleukines and chemokines, etc.). Among all these prognostic indicators, C-reactive protein is now the best analyzed parameter. However, one should take into account that its highest efficacy is reached 3-4 days after onset of disease.

Biomarkers↗
PubMed1997

[Surgical therapy of severe acute pancreatitis].

There is some evidence that the incidence of acute pancreatitis is increasing worldwide. Improved treatment concepts, especially in the severe course of the disease, have significantly reduced formerly high mortality. According to the different clinical courses it is of the utmost importance for the therapeutic approach to this disease to differentiate between mild (morphologically characterized as edema) and severe (intra- and extrapancreatic necroses) as early as possible. In this respect, contrast-enhanced CT scanning and the determination of so-called necrosis indicating parameters (e.g. C-reactive protein) have been established as the "gold-standard". While patients with acute edematous pancreatitis are successfully treated in a normal ward, patients with a proven necrotizing course of the disease should undergo intensive monitoring and maximum intensive care therapy in the ICU. Additionally, these latter patients should receive antibiotics which are capable of penetrating the pancreas and the pancreatic necroses in bactericidal concentrations. It seems more and more evident that only patients under this treatment regimen who develop infected pancreatic necrosis and sepsis are candidates for surgical intervention. Infected pancreatic necrosis can be easily diagnosed with a high level of safety and reliability by fine needle puncture and aspiration of pancreatic necrosis and fluid collections under imaging-guided procedures. Patients with sterile necrosis respond in most cases to intensive care therapy and in these patients the indication for surgery will be only exceptional. Surgery should be performed as late as possible to ensure sufficient demarcation of the necroses. In our experience the best surgical treatment modality for infected pancreatic necrosis is necrosectomy combined with postoperative continuous local lavage of the retroperitoneum. Mortality of severe acute pancreatitis has been reduced under this treatment concept to below 10%.

Acute Disease↗
PubMed1997

[Pancreatic pseudocysts in chronic pancreatitis. Differential diagnosis and therapy].

Pancreatic pseudocysts occur as a complication in the natural course of acute or chronic pancreatitis, with a spontaneous resolution rate of 40% to 60%. The incidence of pseudocysts in the course of chronic pancreatitis amounts to 60%. Pseudocysts have to be differentiated from neoplastic or congenital pancreatic cystic lesions. Careful diagnostic work-up including ERCP and CT scanning is mandatory in the management of pancreatic pseudocysts. The indication for treatment depends on the development of symptoms or complications. Pain is present in up to 90% of all patients, and the rate of complications varies between 2% and 55%. Pancreatic pseudocysts are usually an epiphenomenon of chronic pancreatitis. Pancreatic resection therefore represents a causative treatment. New percutaneous and endoscopic techniques for draining pseudocysts are challenging the previous hegemony of the surgeon. However, so far no prospectively collected data are available comparing the results of interventional and surgical drainage procedures. Therefore, in most symptomatic cases surgery is considered the treatment of choice.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1997

Surgical treatment of infected necrosis.

Over the years, experience has shown that the cornerstone for improved survival in patients with infected pancreatic necrosis is an early, precise diagnosis followed by adequate drainage combined with modern intensive care management. In experienced hands, this goal can be achieved with different surgical approaches, provided that all septic collections are thoroughly removed and that reexploration is performed promptly if there is evidence of ongoing sepsis. If there is any concept preferable, and under what conditions, future large-scale randomized trials with precise and comparable patient stratification will have to demonstrate it.

Debridement↗
PubMed1997

Increased expression of transforming growth factor beta s after acute oedematous pancreatitis in rats suggests a role in pancreatic repair.

BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. AIMS: To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using northern blot analysis and immunohistochemistry, the expression and localisation of TGF beta isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGF beta s was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the pancreatic parenchyma.

Acute Disease↗
PubMed1997

Pathophysiological role of secretory type I and II phospholipase A2 in acute pancreatitis: an experimental study in rats.

BACKGROUND: In human acute pancreatitis two different types of secretory phospholipase A2 (PLA2) have been found. AIM: To analyse the specific pattern of distribution of these PLA2 activities and their pathophysiological role in experimental acute pancreatitis. SUBJECTS AND METHODS: Catalytic activities of secretory type I (pancreatic) and type II (non-pancreatic) PLA2 and the protein concentration of immunoreactive pancreatic PLA2 (IR-PLA2) in serum and pancreatic tissue of rats with cerulein (mild form) and sodium taurocholate (severe form) induced acute pancreatitis were determined. RESULTS: Cerulein infusion caused a significant increase in type I PLA2 activity (p < 0.01) and IR-PLA2 protein concentration (p < 0.01) in serum and pancreas, whereas type II PLA2 activity remained unchanged during the 12 hour observation period. Histology showed no significant tissue destruction. In sodium taurocholate induced acute pancreatitis type II PLA2 activity significantly increased, reaching values over 10-fold higher than controls (p < 0.01), whereas IR-PLA2 protein concentration and type I PLA2 activity were only marginally increased. In this severe model of acute pancreatitis significantly lower values were detected than in the control pancreas (p < 0.002) for PLA2 activity and IR-PLA2 protein concentration. Histology showed parenchymal and fat necroses with haemorrhage, oedema, and inflammatory cell infiltration. CONCLUSIONS: Type I PLA2 activity is dependent on the IR-PLA2 protein concentration in serum and pancreatic tissue. The type II PLA2 activity is not stimulated by cerulein, which indicates an extra-acinar origin of this enzyme. Type II PLA2 activity is significantly increased in sodium taurocholate induced acute pancreatitis indicating its role in the local necrotising process and involvement in the systemic effects in severe acute pancreatitis.

Acute Disease↗
PubMed1997

[Therapy of acute pancreatitis].

Therapy in patients with acute pancreatitis (AP) is primarily conservative and follows the rules of generally accepted principles. A very important basis in the treatment of AP is the interdisciplinary approach to this disease which demands teamwork between clinicians, intensive care specialists and surgeons. Patients with a necrotising course should be hospitalised on the ICU and should receive maximum intensive care measures and antibiotics. Indications for surgical interventions in severe AP are infected pancreatic necrosis and non-response to intensive care therapy.

Acute Disease↗
PubMed1996

Serum phospholipase A2 in patients with multiple organ failure.

Multiple organ failure (MOF) is the most common cause of death in the surgical intensive care unit. We studied the relation of MOF to changes in the concentration of group II phospholipase A2 (PLA2) in serum. Altogether, 215 surgical intensive care patients with multiple injuries, diffuse peritonitis, or sepsis and control patients, who were at a high risk for postoperative sepsis after various surgical interventions, were included in the present prospective study. The clinical performance of the MOF score and the concentrations of group II PLA2 and C-reactive protein (CRP) in serum were studied using receiver operating characteristic (ROC) curves. The group II PLA2 level was considerably above normal in all groups of patients during the first week of observation. There was a highly significant difference in group II PLA2 levels between patients with severe infections (peritonitis and sepsis) and the other patients studied (multiple injuries and elective surgery) (ROC 0.931, P < 0.0001). The concentration of group II PLA2 had a significant positive correlation to the CRP level and body temperature, which indicates that group II PLA2 is an acute phase reactant and that the determination of group II PLA2 is a useful measurement to diagnose severe infections. It was concluded that the concentration of group II PLA2 in serum effectively predicts lethal MOF in patients with multiple injuries after the second day (ROC 0.739, P < 0.01) and in patients with diffuse peritonitis after the fourth day (ROC 0.750, P < 0.02).

Adolescent↗