Biomedical subjects

B Rau

Publications and source records attributed to B Rau.

At least 55 records · Page 3Linked to original sources

PubMed2000

Mutation screening of the chromosome 8q24.3-human activity-regulated cytoskeleton-associated gene (ARC) in idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) comprises a heterogeneous group of disorders, in which a high genetic predisposition and a complex mode of inheritance have been suggested. However, genes, which confer liability to common IGE subtypes including juvenile myoclonic epilepsy (JME) and childhood absence epilepsy (CAE) have not been identified so far. Here, we tested the hypothesis that genetic variation in the human homolog of the <<< >>> (ARC) contributes to the etiology of common IGE disorders. The gene has recently been mapped to chromosome 8q24.3, a region which spans previously identified major IGE susceptibility loci. A systematic search for mutations was performed in 143 patients with a known family history of IGE. However, no evidence for functional variants was found in the ARC coding sequence. Nevertheless, we detected a novel common C489T single nucleotide polymorphism, which provides a useful marker in genetic linkage and association studies. By performing a population- and family-based study we however failed to show significant association between this novel single nucleotide polymorphism and IGE, a finding, which most likely rules out that genetic variation in or close to the ARC gene confers liability to common IGE subtypes.

Adult↗

PubMed2000

[The importance of delay in patients with tumors exemplified by pretreatment of locally advanced rectal carcinoma].

BACKGROUND: With the intention to achieve tumor reduction and thereby increase R0-resection rate, preoperative radiochemotherapy is increasingly applied in locally advanced rectum cancer. Along with the advantages of prior therapy, a delay of surgical treatment occurs which might despite continuing therapy give way to local tumor progression or metastatic disease. PATIENTS AND METHODS: Since 1993 we have treated locally advanced rectum carcinomas by preoperative radiotherapy according to a preoperative study protocol. We analyzed the incidence of local tumor progression or metastases during the 12 weeks of preoperative treatment. Hundred and fifteen patients with histologically proven primary rectum carcinoma without evidence of regional or distant metastases and endosonographically determined infiltration depth of stage T3 or more underwent preoperative radiochemotherapy between 3/1993 and 10/1999. Hundred and eight patients (88 times uT3 and (20 times uT4) have been operated and examined afterwards with respect to response to prior treatment. Before and after preoperative therapy, endorectal ultrasound was performed to evaluate local response. Distant metastatic manifestations were excluded by radiography and ultrasound scanning. RESULTS: A reduction of the infiltration depth was observed in 55 patients (51%). Tumor size remained unchanged in 50 patients (46%). Only 3 patients (3%) showed tumor growth in histological assessment. Fifty-seven patients (53%) showed no change in lymph node status after preoperative therapy, whereas lymph node metastases were detected in 11 patients (10%) who were judged uN0 preoperatively. We discovered metastases in 6 patients (6%) after preoperative therapy. CONCLUSION: During preoperative therapy, tumor progress is not entirely evitable. Considering the lack of precision in pretherapeutic staging diagnostics, we conclude that delays due to therapeutic regimen are responsible for prognostic disadvantage in only a small number of patients.

Antimetabolites, Antineoplastic↗

PubMed2000

[Necrosectomy or anatomically guided resection in acute pancreatitis].

Necrotizing pancreatitis is still associated with considerable morbidity and mortality. Formerly, surgical treatment with early and extensive pancreatic resection has been the standard. Improvements in our understanding of the pathogenesis of the disease and progress in the field of intensive care therapy have made conservative therapy the initial standard in the treatment of necrotizing pancreatitis. A considerable percentage of patients with sterile necrosis can be managed with low morbidity and mortality by conservative treatment without operation. Nevertheless, surgical treatment is indicated in patients with infected necrosis and in sterile necrosis if multiorgan failure persists over a limited period of time despite maximum intensive care therapy. Pancreatic resection should be abandoned for surgical treatment of pancreatic necrosis, as results with regard to morbidity, mortality and long-term outcome are unsatisfactory. Today the surgical standard is careful digital necrosectomy, which must be followed by either postoperatve drainage, repeated open lavage or continuous closed lavage. In experienced hands, all three procedures provide similar results with regard to morbidity and mortality.

Debridement↗

PubMed2000

Prospective comparison of endorectal ultrasound, three-dimensional endorectal ultrasound, and endorectal MRI in the preoperative evaluation of rectal tumors. Preliminary results.

BACKGROUND: The aim of this study was to compare the value of endorectal ultrasound (EUS), three-dimensional (3D) EUS, and endorectal MRI in the preoperative staging of rectal neoplasms. METHODS: Thirty consecutive patients with rectal tumors were assessed by EUS and endorectal MRI. Additionally, three-dimensional ultrasound was performed in a subgroup of 25 patients. EUS data were obtained with a bifocal multiplane transducer (10 MHz) and processed on a 3D ultrasound workstation. MR imaging was carried out with a 1. 5 T superconducting unit using an endorectal surface coil. RESULTS: EUS was carried out successfully in all 30 patients, whereas endorectal MRI was not feasible in two patients. Compared with the histopathological classification, EUS and endorectal MRI correctly determined the tumor infiltration depth in 25 of 30 and 28 patients, respectively. The comparative accuracy of EUS, 3D EUS, and endorectal MRI in predicting tumor invasion was 84%, 88%, and 91%, respectively. EUS, three-dimensional EUS, and endorectal MRI enabled us to assess the lymph node status correctly in 25, 25, and 24 patients, respectively. Both three-dimensional EUS and endorectal MRI combined high-resolution imaging and multiplanar display options. Assessment of additional scan planes facilitated the interpretation of the findings and improved the understanding of the three-dimensional anatomy. CONCLUSION: The accuracy of three-dimensional EUS and endorectal MRI in the assessment of the infiltration depth of rectal cancer is comparable to conventional EUS. One advantage of both methods is the ability to obtain multiplanar images, which may be helpful for the planning of surgery in the future.

Adult↗

PubMed2000

No evidence for association between the KCNQ3 gene and susceptibility to idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) comprises a heterogeneous group of disorders, in which a high genetic predisposition and a complex mode of inheritance have been suggested. Recent identification of ion channel gene mutations in Mendelian epileptic disorders suggests genetically driven neuronal hyperexcitability as one important factor in epileptogenesis. Mutations in two neuronal voltage-gated potassium channel genes (KCNQ2 and KCNQ3) have already been shown to cause epilepsy (BFNC), and we now tested the hypothesis that genetic variation in the KCNQ3 gene confers liability to common IGE subtypes. Length variation of two intragenic polymorphic markers (D8S558 and D8S1835) were therefore assessed in 71 nuclear families ascertained for an affected child. However, the transmission-disequilibrium-test did not show significant differences between the transmitted and non-transmitted parental alleles. Thus, our findings do not provide evidence that genetic variation in the KCNQ3 gene exerts a relevant effect in the etiology of common IGE subtypes.

Alleles↗

PubMed2000

Pathophysiologic role of oxygen free radicals in acute pancreatitis: initiating event or mediator of tissue damage?

BACKGROUND AND OBJECTIVE: Oxidative stress is an important factor in the pathogenesis of acute pancreatitis, as shown in vivo by the beneficial effects of scavenger treatment and in vitro by the potential of free radicals to induce acinar cell damage. However, it is still unclear whether oxygen free radicals (OFR) act only as mediators of tissue damage or represent the initiating event in acute pancreatitis in vivo as well. In the present study the authors aimed to address this issue in an experimental set-up. MATERIALS AND METHODS: Two hundred male Wistar rats were randomly assigned to one of the following experimental groups. In two groups, acute necrotizing pancreatitis was induced by retrograde intraductal infusion of 3% sodium taurocholate. Through the abdominal aorta, a catheter was advanced to the origin of the celiac artery for continuous regional arterial (CRA) pretreatment with isotonic saline (NP-S group) or superoxide dismutase/catalase (NP-SOD/CAT group). In another group, oxidative stress was generated by CRA administration of xanthine oxidase and intravenous administration of hypoxanthine (HX/XOD group). Sham-operated rats received isotonic saline both arterially and intraductally. After observation periods of 5 and 30 minutes and 3 and 6 hours, the pancreas was removed for light microscopy and determination of reduced glutathione (GSH), oxidized glutathione (GSSG), conjugated dienes (CD), and malondialdehyde as a marker for OFR-induced lipid peroxidation as well as myeloperoxidase as a parameter for polymorphonuclear leukocyte accumulation. RESULTS: A significant decrease of GSH was paralleled by an increased ratio of GSSG per total glutathione and elevated CD levels after 5 minutes in the NP-S group versus the sham-operated group. Thereafter, the percentage of GSSG and GSH returned to normal levels until the 6-hour time point. After a temporary decrease after 30 minutes, CD levels increased again at 3 hours and were significantly higher at 6 hours in contrast to sham-operated rats. Myeloperoxidase levels were significantly elevated at 3 and 6 hours after pancreatitis induction. In contrast to NP-S rats, treatment with SOD/CAT significantly attenuated the changes in glutathione metabolism within the first 30 minutes and the increase of CDs after 6 hours. HX/XOD administration lead to changes in levels of GSH, GSSG, and CDs at 5 minutes as well as to increased myeloperoxidase levels at 3 hours; these changes were similar to those observed in NP-S rats. Acinar cell damage including necrosis was present after 5 minutes in both NP groups, but did not develop in HX/XOD rats. In addition, serum amylase and lipase levels did not increase in the latter group. SOD/CAT treatment significantly attenuated acinar cell damage and inflammatory infiltrate compared with NP-S animals during the later time intervals. CONCLUSION: OFRs are important mediators of tissue damage. However, extracellular OFR generation alone does not induce the typical enzymatic and morphologic changes of acute pancreatitis. Factors other than OFRs must be involved for triggering acute pancreatitis in vivo.

Animals↗

PubMed2000

Serum amyloid A versus C-reactive protein in acute pancreatitis: clinical value of an alternative acute-phase reactant.

OBJECTIVES: The acute-phase reactant C-reactive protein (CRP) is currently the serum variable of choice for an early, accurate, and cost-effective severity assessment of acute pancreatitis in the daily clinical routine. Serum amyloid A (SAA) proteins comprise a family of apolipoproteins that constitute another major acute-phase reactant and thus could be a potential alternative to CRP assessment. In the present study we investigated the clinical usefulness of SAA determinations in acute pancreatitis using an automated immunoassay technique. DESIGN: Cohort study, comparing patients with complicated and mild acute pancreatitis; control groups included individuals with further abdominal disorders and healthy volunteers. SETTING: A collaborative study between the department of general surgery and the routine laboratory of the department of clinical chemistry/pathobiochemistry. PATIENTS: We enrolled 66 patients with acute pancreatitis in the present study. Control groups consisted of healthy subjects (n = 30), patients with chronic pancreatitis (n = 20), patients with pancreatic carcinoma (n = 20), and patients with acute appendicitis (n = 20). INTERVENTIONS: Blood samples were collected during 14 consecutive days in patients with acute pancreatitis. A single blood specimen was taken in all control groups after the diagnosis was established. MEASUREMENTS AND MAIN RESULTS: SAA concentrations were 3 mg/L (median; range, 3-93) in healthy subjects. Although SAA and CRP both reached their maximum within 4 days after onset of symptoms in patients with acute pancreatitis, SAA concentrations rose faster above normal ranges and reached 676 mg/L (median; range, 12-1880), higher than CRP, which reached 313 mg/L (median; range, 29-613). As observed for CRP, SAA was significantly higher in patients who developed complications such as necrosis, infection of necrosis, or multiple organ dysfunction syndrome or in patients who died. SAA achieved best results in discriminating between necrotizing pancreatitis and interstitial edematous pancreatitis. However, CRP provided an earlier differentiation between both entities and a significantly better overall accuracy, as shown by receiver operating characteristics analysis. SAA concentrations in patients with chronic pancreatitis were 6 mg/L (median; range, 3-756). In patients with pancreatic carcinoma, SAA concentrations were 7 mg/L (median; range, 3-492), and in patients with acute appendicitis, they were 50 mg/L (median; range, 3-2140). CONCLUSION: SAA is a nonspecific and rapidly produced variable in inflammatory abdominal disorders with a wider dynamic range than CRP. The current assay technique renders SAA an applicable and readily available variable under clinical routine conditions. In cases of acute pancreatitis, however, CRP is still superior to SAA for early and accurate stratification of patients with a complicated course.

Acute Disease↗

PubMed2000

Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications.

BACKGROUND: The time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown. PATIENTS AND METHODS: In a prospective clinical study, we measured the proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1 beta receptor antagonist (IL-1RA), and the soluble IL-2 receptor (sIL-2R), and correlated our findings with organ and systemic complications in acute pancreatitis. In 51 patients with acute pancreatitis admitted within 72 hours after the onset of symptoms, these parameters were measured daily for seven days. In addition, 33 aspirates from ascites and the lesser sac were measured. RESULTS: Sixteen patients had mild acute pancreatitis (AP) and 35 severe AP (Atlanta classification); 18 patients developed systemic complications requiring treatment. All mediators were increased in AP. sIL-2R, IL-10, and IL-6 were significantly elevated in patients with distant organ failure. An imbalance in IL-1 beta/IL-1RA was found in severe AP and pulmonary failure. Peak serum sIL-2R predicted lethal outcome and IL-1RA was an early marker of severity. IL-6 was the best prognostic parameter for pulmonary failure. CONCLUSION: Our results suggest that local mediator release, with a probable IL-1 beta-IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro- and anti-inflammatory mediators. The pattern of local and systemic mediators in complicated AP suggests a role for systemic lymphocyte activation (triggered by local release of mediators) in distant organ complications in severe AP.

Acute Disease↗

PubMed2000

Local and systemic zymogen activation in human acute pancreatitis.

BACKGROUND: Activation of trypsinogen and phospholipase A(2) is an early event in pancreatic inflammation, but little is known about zymogen activation and the severity of human pancreatitis. METHODS: Using a new fluoroimmunoassay we measured trypsinogen activation peptide (TAP) and phospholipase A(2) activation peptide (PROP) in plasma and ascites in 25 patients with acute pancreatitis. TAP, PROP, Pro-PROP and pancreatic PLA(2)-I were measured in plasma for 14 days and in pancreatic necroses, ascitic fluid and pleural effusions. RESULTS: All 16 patients with severe acute pancreatitis (SAP) had pancreatic necrosis, 10 developed systemic complications like sepsis, pulmonary or renal failure, 6 had infected necrosis, and 4 died. All 9 patients with mild pancreatitis (MAP) survived. Plasma TAP on admission was higher in patients with SAP than in those with MAP and increased in infected necroses. It did not correlate with systemic complications. Systemic PROP was not increased in complicated courses but was significantly higher in patients with MAP than in those with SAP on admission. Pro-PROP was higher in patients with SAP than in those with MAP but was not correlated with systemic complications. Plasma pancreatic PLA(2)-I was increased but not different in patients with SAP and those with MAP. In patients with pancreatic necrosis, TAP and PROP were highest, while in those with post-acute pancreatic abscess, only PROP and Pro-PROP were high. In patients with pleural effusion, TAP was low and PROP/ Pro-PROP were high. CONCLUSION: Trypsinogen and PLA(2)-I activation are early events in acute pancreatitis and the activation peptides can be detected in plasma. In the pancreas, trypsinogen activation is accompanied by PLA(2)-I activation in patients with pancreatic necrosis. However, in our study, organ complications in SAP patients was not associated with increased plasma PROP.

Acute Disease↗

PubMed2000

[Preoperative radiochemotherapy of rectal carcinoma. Current status].

BACKGROUND: In locally advanced rectal cancer RO-resectability is limited and outcome is combined with a relatively high rate of local recurrences. This paper focuses on experiences with preoperative (neo-)adjuvant therapy and the potential improvement of treatment results. PATIENTS AND METHODS: Different therapy regimen were demonstrated under consideration of therapeutic induced side effects, treatment response (downstaging) in relation to resectability, recurrence free and overall survival. RESULTS: The rate of treatment induced toxicity of preoperative radio-(chemo-)therapy in locally advanced rectal cancer is acceptable with regard to the obtained treatment results. Through the pretreatment it was possible to gain a downstaging by nearly 60%. The frequency of local recurrence is significantly reduced by preoperative radiotherapy, and combined radiochemotherapy possibly increases the disease free survival. In what extent the results of treatment could be improved through hyperthermia and/or consecutive postoperative chemotherapy, is proved at present. CONCLUSIONS: Preoperative radio-(chemo-)therapy should be increasingly introduced into the standard treatment regimen of locally advanced rectal cancer and has to be optimised within the scope of further studies.

Disease-Free Survival↗

PubMed1999

The role of polymorphonuclear leukocytes and oxygen-derived free radicals in experimental acute pancreatitis: mediators of local destruction and activators of inflammation.

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

Acute Disease↗

PubMed1999

Scanning E-field sensor device for online measurements in annular phased-array systems.

PURPOSE: A measurement device for noninvasive and simultaneous control of antennas during regional radiofrequency (rf) hyperthermia and, subsequently, the estimation of the power distribution in the interior of patients are essential preconditions for further technological progress. Aiming at this, the feasibility of an electro-optical electric field sensor was investigated during clinical rf hyperthermia. MATERIAL AND METHODS: The electro-optical electric field (E-field) sensor is based on lithiumniobate crystals and the Mach-Zehnder interferometer structure, and was tested in an earlier phantom study. For this study, a mechanical scanning device was developed allowing the registration of the E-field during clinical application. Data were recorded along a curve in the water bolus of the SIGMA 60 applicator of the annular phased-array system BSD-2000 (BSD Medical Corp., Salt Lake City, UT) close to the base points of the flat biconical dipole antennas. The results were compared with modeling calculations using the finite-difference time-domain (FDTD) method. For the latter, different antenna models were assumed. For systematic registration of the E-field curves in amplitude and phase, we employed an elliptical lamp phantom with fat-equivalent ring (filled with saline solution) and an elliptical polyacrylamide phantom with acrylic glass wall. Further measurements were carried out during the treatment of 5 patients with 20 hyperthermia treatments. RESULTS: Data of both phantom and patient measurements can be satisfactorily described by the FDTD method, if the antenna model is refined by taking into account the conical form of the dipoles and the special dielectric environment of the feeding point. Phase deviations can be entered ex posteriori for correction in the calculation algorithm. A comparison of amplifier power measurement (forward and backward power) and bolus E-field scans near the antenna base points demonstrates that E-field measurements between antennas and patient are a necessity for the appropriate characterization of antenna radiation properties. These measurements are sensitive to variations of the lossy medium in position and shape, and can be correctly predicted with current models. However, the differences between different patients are moderate and unspecific in both calculations and measurements, with fluctuations at maximum of 30 degrees in phases and 40% in amplitudes. CONCLUSIONS: The measurement method presented here turned out to be a practical tool for online registration of E-fields in phases and amplitudes along arbitrary curves in a water bolus or phantom. It can be utilized to evaluate antenna design and modeling calculations and leads, thus, to a better understanding of complicated multiantenna systems. In clinical routine, it can be employed as input for patient-specific hyperthermia planning and, finally, for the realization of online control with subsequent optimization of the power distribution in the patient.

Algorithms↗

PubMed1999

Hyperthermia for treatment of rectal cancer: evaluation for induction of multidrug resistance gene (mdr1) expression.

Environmental stress factors, such as heat, may induce multidrug resistance gene (mdr1) expression, which could result in the disadvantageous multidrug resistance (MDR) phenotype. To evaluate this possibility in a clinical situation, we investigated mdr1 gene expression in patients with locally advanced rectal cancer who underwent preoperative radio-chemo-thermo-therapy (RCTT). Patients were classified into groups according to the treatment schedule of RCTT vs. radio-chemo-therapy (RCT) without hyperthermia (control group). Expression of the mdr1 gene was analyzed in tumors and normal rectal tissues prior to and post-treatment (RCTT or RCT, respectively) by means of semi-quantitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The data were correlated with therapeutic response and survival parameters. Based on our evaluation criteria, in 2 of 19 tumors of the RCTT group, mdr1 gene expression was increased more than 2-fold; in 3 of 19 tumors of this group, however, mdr1 expression was decreased more than 2-fold. In the patient control group, levels of mdr1 gene expression were reduced in 2 of 8 tumors. Thus, hyperthermia combined with RCT (RCTT) in comparison with RCT alone does not lead to an increase in mdr1 gene expression in patients with locally advanced rectal cancer within the preoperative treatment schedule. The risk of inducing the classical multidrug resistance phenotype by hyperthermia was thus minimal in this clinical setting. Subsequent adjuvant chemotherapy should thus not be hindered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Experiences in HCV-NAT screening prior to releasing cellular components by the German Red Cross Blood Transfusion Service of Baden-Württemberg.

In this report we present the accumulated data on nucleic acid testing (NAT) for hepatitis C virus (HCV) RNA of blood donations by the Blood Transfusion Service of Baden-Württemberg in the period between March 1997 and March 1999. An extra barcoded blood sample was collected from each donor. Samples were tested by NAT in mini-pools of maximally 96 samples. First-time and repeat donors were tested separately. RT/HCV-PCR was performed with the COBAS HCV Amplicortrade mark, versions 1.0 and 2.0 from Roche Diagnostic Systems. Many modifications have been introduced to the original protocol since the implementation of NAT screening aiming at an increase in the sensitivity and specificity of the assay. NAT positive pools containing serologically positive samples were detected. Initially, reactive pools were identified that could not be confirmed by secondary pooling and single testing procedures. So far, no serologically negative but NAT positive sample has been found.

Blood Banks↗

PubMed1999

Accuracy of endorectal ultrasound after preoperative radiochemotherapy in locally advanced rectal cancer.

OBJECTIVES: Factors limiting the accuracy of endorectal ultrasound in staging, locally advanced primary rectal cancer after preoperative neoadjuvant radiochemotherapy (RCT) were evaluated. METHODS: Patients (n = 84) with initial locally advanced rectal cancer (uT3/uT4) undergoing R0 resection were investigated after preoperative treatment that combined radiotherapy up to 45 Gy with two cycles of chemotherapy (5-FU and leucovorin on d 1-5 and 22-28). At 4 to 6 weeks after completion of RCT and before tumor resection, preoperative endoluminal ultrasound was performed. RESULTS: The accuracy to predict the depth of tumor infiltration (T-category) was found to correlate with downstaging. The T-category was correctly staged before surgery in 15 of the 51 responders (29%) and in 27 of 33 nonresponders (82%), whereas misinterpretation occurred in 36 of the responders (71%) and in 6 of the nonresponders (18%) (p < 0.001). Neither tumor distance from anal verge nor tumor location correlated with the staging accuracy. Lymph node involvement was correctly assessed in 48 patients (57%). Wall invasion was correctly ascertained in 42 patients (50%), with under estimation in 11 patients (13%) and overestimation in 31 patients (37%). CONCLUSIONS: After radiochemotherapy, endosonography does not provide a satisfactory accuracy for preoperative staging of rectal cancer. New interpretation and diagnostic criteria are needed for the prediction of treatment response.

Adenocarcinoma↗

PubMed1999

Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis.

BACKGROUND: The risk factors predisposing to organ failure in patients with necrotizing pancreatitis remain unclear. The relationship between the extent of pancreatic necrosis, the presence of infection and the incidence of organ failure was analysed. METHODS: In a retrospective review, the occurrence of pulmonary insufficiency, renal insufficiency, shock, sepsis/sepsis-like syndrome (SLS) and coagulopathy was evaluated in 273 patients with necrotizing pancreatitis, and a comparison was made between patients with sterile or infected necrosis. Additionally, the relation between the incidence of organ failure and extent of pancreatic parenchymal necrosis was investigated by classifying the patients into three groups according to the amount of necrotic tissue found by contrast-enhanced computed tomography (group 1, extent less than 30 per cent; group 2, 30-50 per cent; group 3, more than 50 per cent). RESULTS: Organ failure was more frequent in patients with infected necrosis than in those with sterile necrosis. Differences were found in the incidence of pulmonary insufficiency, sepsis/SLS and coagulopathy. Organ failure occurred more frequently in group 3 than in group 2 or 1 (95 versus 79 and 66 per cent; P = 0.0004). The extent of infected necrosis was not related to the incidence of organ failure (group 1, 88 per cent; group 2, 86 per cent; group 3, 96 per cent). However, there was a relation between the incidence of organ failure and the extent of sterile necrosis (group 1, 59 per cent; group 2, 74 per cent; group 3, 94 per cent; P = 0.0001). Multivariate analysis confirmed the presence of infection and the extent of necrosis as independent determinants of organ failure. CONCLUSION: The incidence of organ failure is determined by both bacterial infection and extent of necrosis. The incidence of organ failure is determined by the extent of necrotic parenchyma in patients with sterile necrosis. Infected necrosis is associated with a high incidence of organ failure irrespective of the extent of necrosis.

Acute Kidney Injury↗

PubMed1999

Systemic lymphocyte activation modulates the severity of diet-induced acute pancreatitis in mice.

To examine the role of lymphocyte activation in the development of local and systemic complications in acute pancreatitis, we compared disease severity of choline-deficient, 0.5% ethionine supplemented (CDE) diet-induced acute pancreatitis in T- and B-cell deficient SCID mice and immunocompetent C.B-17 mice. Twenty-five female SCID and 17 female C.B-17 mice were fasted for 24 h and fed a CDE diet for 72 h. Twenty SCID and 12 C.B-17 mice were bled and their organs removed for histologic evaluation. Five control animals of both kinds were fed a regular diet for 6 days. Lung, kidney, and pancreas were examined microscopically, and pancreatic damage scored. Apoptosis was detected by DNA nick-end labeling and confirmed by DNA laddering. Trypsinogen-activation peptide was measured by enzyme-linked immunosorbent assay (ELISA), and the catalytic activity of PLA2 was determined by a radiometric assay. Four-day mortality was 10% in SCID and 33% in C.B-17 mice, and 10-day mortality was 0 in SCID and 60% in C.B-17 mice. SCID mice had mild pulmonary damage, whereas pulmonary injury was severe in C.B-17 mice. Pancreatic damage was severe in both groups. Even though in situ staining of apoptotic cells was found in all pancreatitis animals, apoptosis was confirmed by DNA laddering only in C.B-17 mice. In SCID mice, apoptotic cell staining positively correlated with necrosis (r = 0.91; p < 0.001). Plasma TAP and PLA2 catalytic activity did not differ significantly between the groups. In conclusion, the absence of T and B lymphocytes prevents severe pulmonary injury resulting from acute pancreatitis but does not influence pancreatic or renal damage. Our results suggest that systemic lymphocyte activation does not affect the initiating events that trigger pancreatic injury but modulates the systemic response, in particular, pulmonary injury caused by acute pancreatitis.

Acute Disease↗

PubMed1999

New approaches in surgical management of severe acute pancreatitis.

Despite many prospective randomized clinical studies a specific pharmacotherapy for severe acute pancreatitis is not in sight. To date, the only possibility to influence the prognosis of this severe illness is early diagnosis and prevention of intra- and extrapancreatic necrosis and its subsequent infection. In severe necrotizing pancreatitis the incidence of infected necrosis amounts to 40-70% of all patients within 3 weeks. Thereby, the clinical picture often varies to large extent. Ultrasonographically or computer tomography-guided fine-needle aspiration (FNAC) is a fast and reliable technique for diagnosis with an overall sensitivity of 88% and specificity of 90%. This method should however not be applied too early in the course of necrotizing pancreatitis. Since infection of pancreatic necrosis determines significantly the prognosis of disease, various studies have assessed the efficacy of prophylactic antibiotic treatment in patients. Three prospective randomized studies have shown that prophylaxis significantly minimizes septic complications, only in one study, however, the mortality rate could be improved. Although randomized studies are still mandatory to resolve the controversy, it seems justified to recommend prophylaxis with antibiotics which are capable of penetrating the pancreatic tissue and juice. Sterile necrosis should be treated conservatively, with prophylactic antibiotic treatment for as long as possible. Only if patients worsen despite intensive care medicine, surgical debridement should be considered. In contrast, in patients with infected necrosis immediate surgery is in most cases mandatory. Although in one prospective study conservative treatment did not lead to an enhanced mortality rate, possible delay of surgical treatment may endanger the patient. In order to improve the prognosis of the disease, timely and adequate treatment in specialized units provides the best chances for a good prognosis whereby the severely ill patient should not be treated according to a scheme but to his/her individual needs.

Antibiotic Prophylaxis↗