Antimicrobial resistance of Streptococcus dysgalactiae, Streptococcus agalactiae, and Streptococcus canis in quarter milk samples from Bavaria, Southern Germany, between 2012 and 2022.

The objective of this study was to analyze the in vitro antimicrobial resistance (AMR) of Streptococcus (Sc.) dysgalactiae, Sc. agalactiae, and Sc. canis over a 10-year period from 2012 to 2022 against the most commonly used antimicrobial agents. For this purpose, all quarter milk samples (QMS) submitted to the milk laboratory of the Bavarian Animal Health Service (TGD) were analyzed. Each QMS was tested using the California Mastitis Test (CMT) and categorized as negative (N), subclinical (S), or clinical (C) mastitis if the milk character was abnormal. Samples with Sc. dysgalactiae, Sc. agalactiae, or Sc. canis were included and a subset of isolates were further tested for in vitro antimicrobial resistance by breakpoint analysis with broth microdilution. Sc. dysgalactiae (61%, n = 65,750) was the most abundant pathogen among those 3 species, followed by Sc. agalactiae (28%, n = 30,486), and Sc. canis (11%, n = 11,336). All 3 species showed the highest resistance to the same 4 antimicrobial agents: erythromycin, marbofloxacin, pirlimycin, and cefalexin/kanamycin with varying degrees of resistance. Throughout the study period, Sc. dysgalactiae, Sc. agalactiae, and Sc. canis were largely susceptible to the remaining antimicrobial agents tested (penicillin, amoxicillin-clavulanate, oxacillin, cefazolin, cefoperazone, cefquinome). Only less than 14% of isolates of Sc. dysgalactiae and Sc. canis were resistant against any of the antimicrobials tested. Sc. agalactiae was the species with the highest percentage of resistant isolates. While the percentage of resistant isolates from Sc. canis and Sc. dysgalactiae decreased, the percentage of resistant Sc. agalactiae isolates increased since 2017. In summary, most isolates were not resistant to the most commonly used antimicrobial agents for mastitis therapy, including ß-lactam antibiotics and penicillin should remain the first-choice therapy against streptococcal mastitis.

Changes in antimicrobial resistance of Staphylococcus aureus in bovine quarter milk samples from Southern Germany between 2012 and 2022.

The objective of this study was to describe the in vitro resistance of Staphylococcus (S.) aureus from bovine quarter milk samples obtained by the udder health laboratory of the Bavarian Animal Health Services between 2012 and 2022. All S. aureus samples were tested for ß-lactamase production and only forwarded to further microbroth susceptibility testing either if the ß-lactamase result was positive or upon explicit request by the submitter. The growth of most S. aureus isolates was inhibited at the lowest evaluated minimum inhibitory concentration (MIC) of tested antimicrobials, with the MIC50 and MIC90 mostly beneath the respective breakpoint. On average, about a quarter (24%, n = 5,718) of tested isolates was resistant to erythromycin. However, the prevalence of resistant isolates dropped from 53% (n = 1,018) in 2012 to 8% (n = 113) in 2022. The second highest prevalence of in vitro resistance was to penicillin (17%, of all isolates tested for ß-lactamase production, n = 28,069). Less than 14% of isolates were resistant to the remaining assessed antimicrobial agents (cefoperazone, pirlimycin, kanamycin-cefalexin, marbofloxacin, amoxicillin-clavulanate, cefquinome, or cefazolin, respectively). Over the years, 4% (n = 959) of the S. aureus isolates selected for microbroth susceptibility testing (and 0.8% (n = 1,392) of all submitted S. aureus isolates) were methicillin-resistant S. aureus (MRSA), and 5% (n = 1,162) of S. aureus isolates were multidrug-resistant. However, there was an overall trend toward fewer resistant isolates. These findings are consistent with those of several European monitoring programs that reported a slight decrease of AMR of bovine S. aureus in countries where antibiotic use in veterinary medicine was reduced. Notably, isolates of clinical mastitis cases were consistently less likely to express in vitro resistance than isolates obtained from milk of healthy cows or subclinical mastitis cases. In conclusion, antimicrobial resistance (AMR) of S. aureus was decreasing and penicillin should remain the first-choice antimicrobial in the attempt of treating S. aureus intramammary infections in Bavaria.

Multiple cases of methicillin-resistant CC130 Staphylococcus aureus harboring mecC in milk and swab samples from a Bavarian dairy herd.

The discovery of a new mecA homolog, mecC, necessitates a modification of diagnostic procedures for the identification of methicillin-resistant Staphylococcus aureus (MRSA), as most assays used for the genotypic and phenotypic mecA detection cannot currently recognize mecC. Although the prevalence, distribution, and importance of mecC are not yet completely understood, an exchange of mecC-MRSA between humans and animals seems possible. All previously reported observations of mecC-positive strains have been sporadic. To the best of our knowledge, this is the first report about multiple cases of mecC-positive Staph. aureus in 1 dairy herd. Clonal complex 130 Staph. aureus harboring mecC were found in milk samples from 16 of 56 lactating cows kept in a herd in Bavaria, Germany. Almost all quarter milk samples positive for mecC-MRSA had the lowest possible California Mastitis Test score; composite somatic cell counts obtained from monthly milk recordings showed a mean of 51,600 cells/mL in mecC-MRSA affected cows. Additionally, mecC-positive clonal complex 130 Staph. aureus were detected in swab samples from the mammary skin and a teat lesion of 1 cow from this herd. This report suggests that mecC-carrying strains are able to spread among livestock, and that they have the ability to cause multiple cases in single herds. Therefore, future studies targeting MRSA in dairy cows need to consider mecC.

Effect of virtual endoscopy simulator training on performance of upper gastrointestinal endoscopy in patients: a randomized controlled trial.

BACKGROUND: Skills in gastrointestinal endoscopy mainly depend on experience and practice. Patients upon whom trainees perform their first endoscopic examinations are likely to suffer more discomfort and prolonged procedures. Training on endoscopy simulators may reduce the time required to reach competency in patient endoscopy. PATIENTS AND METHODS: Residents in internal medicine without experience of endoscopy were randomized to a group who trained on a simulator before conventional training (group S) or one that received conventional training only (group C) before starting upper gastrointestinal endoscopy in patients. After endoscopy, discomfort and pain were evaluated by patients, who were blind to the beginners' training status. Results in terms of time, technique (intubation, pyloric passage, J-maneuver), and diagnosis of pathological entities were evaluated by experts. RESULTS: From 2003 to 2007, 28 residents were enrolled. Comparing group S with group C in their first ten endoscopic examinations in patients, time taken to reach the duodenum (239 seconds (range 50 - 620) vs. 310 seconds (110 - 720; P < 0.0001) and technical accuracy ( P < 0.02) were significantly better in group S. Diagnostic accuracy did not differ between the groups. Fourteen residents (7 simulator-trained, 7 not simulator-trained) continued endoscopy training. After 60 endoscopic examinations, investigation time was still shorter in group S. Technical and diagnostic accuracy improved during on-patient training in both groups; here differences between groups were no longer observable. There were no significant differences in discomfort and pain scores between the groups after 10 and after 60 endoscopies. Discomfort and pain were higher than for endoscopy performed by experts. CONCLUSION: This randomized controlled trial shows that virtual simulator training significantly affects technical accuracy in the early and mid-term stages of endoscopic training. It helps reduce the time needed to reach technical competency, but clinically the effect is limited. Simulator training could be useful in an endoscopy training curriculum but cannot replace on-patient training.

Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.

OBJECTIVE: Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS: A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS: Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3 ± 24.6, 34.4 ± 35.1, 61.1 ± 37.9; P < 0.001), fewer subsequent therapies (0.43 ± 1.0, 2.1 ± 2.4, 3.1 ± 3.0; P ≤ 0.001), and a longer relapse-free interval (P = 0.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P ≤ 0.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P = 0.023). CONCLUSIONS: Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.

HIV-HCV co-infected patients with low CD4+ cell nadirs are at risk for faster fibrosis progression and portal hypertension.

Patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) are fraught with a rapid fibrosis progression rate and with complications of portal hypertension (PHT) We aimed to assess the influence of immune function [Centers of Disease Control and Prevention (CDC) stage] on development of PHT and disease progression in HIV-HCV co-infection. Data of 74 interferon-naïve HIV-HCV co-infected patients undergoing liver biopsy, measurement of portal pressure and of liver stiffness and routine laboratory tests (including CD4+ cell count, HIV and HCV viral load) were analysed. Time of initial exposure (risk behaviour) was used to assess fibrosis progression. Fibrosis progression, time to cirrhosis and portal pressure were correlated with HIV status (CDC stage). HIV-HCV patients had rapid progression of fibrosis [0.201 +/- 0.088 METAVIR fibrosis units/year (FU/y)] and accelerated time to cirrhosis (24 +/- 13 years), high HCV viral loads (4.83 x 10(6) IU/mL) and a mean HVPG at the upper limit of normal (5 mmHg). With moderate or severe immunodeficiency, fibrosis progression was even higher (CDC-2 = 0.177 FU/y; CDC-3 = 0.248 FU/y) compared with patients with higher CD4+ nadirs (CDC-1 = 0.120 FU/y; P = 0.0001). An indirect correlation between CD4+ cell count and rate of fibrosis progression (R = -0.6654; P < 0.001) could be demonstrated. Hepatic venous pressure gradient (HVPG) showed early elevation of portal pressure with median values of 4, 8 and 12 mmHg after 10, 15 and 20 years of HCV infection for CDC-3 patients. Patients treated with highly active anti-retroviral therapy (HAART) had similar rates of progression and portal pressure values than patients without HAART. Progression of HCV disease is accelerated in HIV-HCV co-infection, being more pronounced in patients with low CD4+ cell count. A history of a CD4+ cell nadir <200/microL is a risk factor for rapid development of cirrhosis and PHT. Thus, HCV treatment should be considered early in patients with HIV-HCV co-infection and largely preserved CD4+ cell counts.

Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C.

Antiviral treatment results in a sustained virologic response (SVR) in 50-75% of patients with chronic hepatitis C. Long-term follow up studies have observed ongoing SVR in the overwhelming majority of them. Thus chronic hepatitis C is considered 'cured' if an SVR is achieved. Consequently, it is expected that in sustained virologic responders long-term complications of hepatatic C virus (HCV) related chronic liver disease including hepatocellular carcinoma are eliminated or have a decreased incidence. We report on five patients (three from Austria, two from USA) who developed hepatocellular carcinoma during follow up (3-6 years) after achieving SVR. During follow up and at diagnosis all were HCV-RNA neg. None of the patients had other liver diseases. One patient presented with bilateral adrenal metastasis, the remaining four with large hepatic tumours. Three patients were noncirrhotic at the start of treatment at the time of tumour diagnosis. Successful antiviral treatment in HCV patients does not prevent development of hepatocellular carcinoma even in non-cirrhotic livers. Long-term follow up of patients with SVR is mandatory and should include surveillance for hepatocellular carcinoma.

Efficacy of interferon in immunocompromised HCV patients after liver transplantation or with HIV co-infection.

BACKGROUND: Interferon (IFN)-based antiviral therapy is increasingly used in immunocompromised patients with chronic hepatitis C after orthotopic liver transplantation (OLT) and HIV-HCV co-infection. Differences in early viral kinetics have not been compared in these patients. MATERIALS AND METHODS: We retrospectively analysed 76 patients (31 OLT, 20 HIV-HCV and 25 HCV control patients) undergoing IFN sensitivity testing before starting antiviral therapy with pegylated IFN-alpha 2a (180 microg week(-1)) plus ribavirin (0.8-1.2 g day(-1)) for 48 weeks. We compared baseline parameters, response to IFN and treatment outcome between the groups and assessed the influence of specific calcineurin inhibitors in OLT patients and immune status in HIV-HCV patients on treatment response. RESULTS: Viral loads pretherapy were higher in OLT compared to nontransplanted HCV controls (P = 0.003). The same trend was present in HIV-HCV (P = 0.09). The log-drop after test dose was less in OLT compared to HCV (P = 0.02), while no significant difference was found between HIV-HCV and HCV. In HIV-HCV patients viral load log-drop correlated significantly with CD4(+) cell counts (P = 0.001). No difference in viral load pretherapy, log-drop and treatment outcome was noted between different calcineurin inhibitors in OLT patients. Sustained virological response rates were 28% in OLT, 50% in HIV-HCV and 56% in HCV patients. CONCLUSIONS: Immunosuppression results in high HCV viral loads. Initial efficacy of IFN is significantly impaired in OLT patients, but not in HIV-HCV with largely preserved CD4(+) cell counts. Sustained virological response rates of 28% in OLT patients are suboptimal, but encouraging results are shown for HIV-HCV patients with relatively high CD4(+) cell counts.

Safety and efficacy of endoscopic balloon dilation for treatment of Crohn's disease strictures.

BACKGROUND AND STUDY AIMS: Strictures are a substantial cause of morbidity in patients with Crohn's disease. Endoscopic balloon dilation is a therapeutic option in limited strictures to avoid intestinal surgery, although there have been few reports regarding the long-term outcome. PATIENTS AND METHODS: Balloon dilation was scheduled for 46 patients (26 women, 20 men; median age 34) with Crohn's-associated symptomatic and radiographically confirmed intestinal stenosis. The study plan envisaged up to four consecutive treatments within the first 2 months until relief of symptoms, and thereafter dilations depending on clinical requirements. RESULTS: Dilation was not possible in seven of the 46 patients (15 %), due to technical problems (n = 2), internal fistulas (n = 3), or absence of a stenosis (n = 2). Thirty-nine patients received at least one treatment. The site of obstruction was the ileocolonic anastomosis in 23 of the 39 patients (59 %) and surgically untreated areas in 16 patients (41 %). After the initial dilation series (median 1, interquartile range 1-2), strictures were traversed in 37 of the 39 patients (95 %). During a median follow-up period of 21 months (range 3-98 months), 24 of the 39 patients (62 %) underwent a repeat intervention, including 12 (31 %) with repeat dilation, 11 (28 %) with surgical resection, and one patient who received an intestinal stent. The cumulative percentages of patients without a repeat intervention or surgery at 6, 12, 24, and 36 months were 68 %, 48 %, 36 %, and 31 %, and 97 %, 91 %, 84 % and 75 %, respectively. Two perforations and one case of severe bleeding were seen in the 73 dilation procedures (4 %) performed. CONCLUSIONS: Endoscopic balloon dilation is a safe and effective method that allows surgery to be avoided in approximately 75 % of patients with Crohn's-associated short intestinal strictures. However, recurrent symptoms frequently make it necessary to repeat the procedure.

Suppression of haematopoiesis during therapy of chronic hepatitis C with different interferon alpha mono and combination therapy regimens.

BACKGROUND: Treatment of chronic hepatitis C with interferon (IFN)-alpha and ribavirin has haematotoxic effects. We evaluated the effects of four different IFN/IFN-ribavirin treatment regimens on haematopoiesis. METHODS: Haematopoiesis was studied in 133 patients with chronic hepatitis C receiving IFN-alpha2b alone (group A) or in combination with ribavirin (group B), pegylated IFN-alpha2a (group C), or pegylated IFN-alpha2b (group D) in combination with ribavirin. RESULTS: At week 4, haemoglobin levels were diminished in all groups receiving combination therapy. In the monotherapy group, haemoglobin decreased slightly after eight weeks. In all groups, haemoglobin remained diminished throughout therapy. In all patients, leucocytes (while blood cells) decreased after four weeks and remained low during treatment. Platelets (peripheral platelet count (PPC)) were decreased in all groups after four weeks and remained below baseline levels during therapy in group A, C, and D whereas in group B PPC recovered early and reached baseline levels at week 16 of therapy. Concomitantly with the decreases in haemoglobin and PPC, erythropoietin increased in all groups receiving combination therapy and thrombopoietin in all groups. Patients treated with pegylated IFN-alpha2a and those who received pegylated IFN-alpha2b combination therapy differed only in leucopoiesis, whereas erythropoiesis and thrombopoiesis were comparable. CONCLUSION: IFN-alpha based therapies are associated with a decrease in all three haematopoietic lineages, irrespective of the type of therapy used. The stronger suppressive effect of pegylated IFN-alpha2a on leucopoiesis could be due to a dose effect. Overall, concentrations of endogenous haematopoietic growth factors are increased but can only partially alleviate haematotoxicity. Potential uses of exogenous haematopoietic growth factors and their impact on the virological response need to be explored.

Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection.

Immune response to viral infection is an important determinant of liver injury in chronic hepatitis C (CHC). Experimental and clinical data suggest a protective role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4) was investigated on (i) susceptibility to CHC, (ii) progression of hepatic fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1 infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage 1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3 in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found between the SNP4 allele and the presence of cirrhosis (P=0.01). Homozygous SNP4 individual variants segregated within the cirrhosis group (P=0.03). We found neither an association with SNP3 nor with the necroinflammatory disease activity (as measured by ALT levels) nor with the response to antiviral therapy. Our work implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic cirrhosis in HCV genotype-1 infection.

Short- and long-term effects of therapy with interferon-alpha and pegylated interferon-alpha/ribavirin on platelet plug formation and von Willebrand factor release in patients with chronic hepatitis C.

BACKGROUND: A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy. AIM: To evaluate the effect of pegylated interferon-alpha administration on platelet plug formation and von Willebrand factor antigen release in patients with chronic hepatitis C. METHODS: Thirty patients with chronic hepatitis C (genotype 1; fibrosis 1-3: n = 16, cirrhosis: n = 14) received a single dose of 9 MU interferon-alpha2a, followed by weekly administration of 180 mug of pegylated interferon-alpha2a/ribavirin for 48 weeks. Platelet counts, platelet function (collagen-epinephrine-induced closure time) and von Willebrand factor antigen were measured. RESULTS: Platelet counts and collagen-epinephrine-induced closure time decreased by 13% and 16%, respectively, 24 h after the first dose of interferon-alpha2a, and von Willebrand factor antigen levels increased by 31% (P < 0.01) compared with baseline. During a 48-week observation period, platelet counts decreased by a maximum of 33% (P < 0.001), von Willebrand factor antigen levels increased by 69% (P < 0.001) whereas collagen-epinephrine-induced closure time did not change. In noncirrhotic patients, the increase of von Willebrand factor antigen levels was maintained throughout therapy without a change in collagen-epinephrine-induced closure time. In contrast, in cirrhotics, von Willebrand factor antigen levels did not increase, while collagen-epinephrine-induced closure time was prolonged. CONCLUSION: Single-dose interferon-alpha decreases platelet counts but improves platelet function, possibly by the release of von Willebrand factor antigen. Accordingly, long-term antiviral treatment had no effect on collagen-epinephrine-induced closure time, despite the decrease in platelet count in noncirrhotic patients. Such a compensation of decreased platelet counts by increased von Willebrand factor antigen level did not occur in cirrhotics.

Mycobacterium avium ssp. paratuberculosis--combined serological testing and classification of individual animals and herds.

Several serological tests for detection of antibodies to Mycobacterium avium ssp. paratuberculosis, which is the causative agent of Johne's disease are validated, some of which are available commercially. These tests differ in sensitivity and specificity. Test results reported to farmers or veterinarians are therefore dependent upon the test in use. In the present study, three commercially available tests are used to test 2748 bovine sera from 119 Bavarian herds serologically. Serological results are compared with individual animals and on herd level. A scheme for serological testing and classification of herds as well as of individual animals based on a combination of serological test results is proposed.

Bradycardia and sinus arrest during percutaneous ethanol injection therapy for hepatocellular carcinoma.

BACKGROUND: Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC) and considered a safe procedure, with severe complications occurring rarely. Cardiac arrhythmias have not been reported to date. Aim of the study was to investigate the occurrence of dysrhythmias during PEI. PATIENTS AND METHODS: Twenty-six consecutive patients with inoperable HCC were included. During ultrasound-guided PEI with 95% ethanol, electrocardiogram (ECG) monitoring was performed before starting and continuously during PEI. RESULTS: During PEI a significant reduction in mean heart rate (> 20%) was seen in 15 of 26 (58%) patients. In 11 of 26 patients (42%) occurrence of sinuatrial block (SAB) or atrioventricular block (AVB) was observed after a median time of 9 s (range 4-50) from the start of PEI with a median length of 24 s (range 12-480). Clinical symptoms were seen in two patients, including episodes of unconsciousness, seizure-like symptoms in both and a respiratory arrest during PEI in one patient, requiring mechanical ventilation. In four of 12 patients with repeat interventions, dysrhythmias were reproducible during monthly performed procedures. There was a significant association between the occurrence of SAB or AVB and the amount of instilled alcohol (P = 0.03) and post-PEI serum ethanol levels (P = 0.03). CONCLUSIONS: Bradycardia and block formation occur frequently during PEI. These symptoms could be explained by a vasovagal reaction and/or the direct effect of ethanol on the sinus node or the right atrial conduction system. Ethanol dose is an important factor for the occurrence of SAB/AVB. ECG-monitoring seems mandatory during PEI. Prophylactic use of intravenously administered Atropine might be useful.

Diagnosing colitis: a prospective study on essential parameters for reaching a diagnosis.

BACKGROUND AND STUDY AIMS: It is generally believed that making a correct histological diagnosis of colitis at colonoscopy requires segmental mucosal biopsies, information on the endoscopic features, and clinical data. This prospective study was carried out to determine the essential parameters required for an accurate diagnosis of colitis. PATIENTS AND METHODS: Two hundred consecutive patients with suspected or established colitis who underwent colonoscopy were prospectively examined. A double biopsy was taken at a macroscopic site of typical inflammation, or, if no abnormalities could be found, from normal mucosa. In addition, segmental biopsies were obtained. Endoscopic features and the patient's clinical history and symptoms were recorded. Histology was analyzed by providing the pathologist with the double-biopsy sample, segmental biopsies, and endoscopic and clinical information in a segmental fashion. Changes in the diagnoses were noted after each step of the analysis. RESULTS: Colitis was diagnosed in 152 patients (76 %). Double-biopsy examination provided the correct final diagnosis in 66 % of cases. After assessment of the segmental biopsies, the diagnosis had to be changed in 26 % of cases. Information on the endoscopic features altered the diagnosis in 2.5 %. Finally, the diagnosis was changed in an additional 5.5 % of cases after clinical data (the patient's history and symptoms) had been provided. CONCLUSIONS: Segmental biopsy specimens are essential for the differential diagnosis of intestinal inflammation. Information on the endoscopic features and clinical data are useful in differentiating some forms of colitis.

Donor dependent, interferon-gamma induced HLA-DR expression on human neutrophils in vivo.

Neutrophils are effector cells of innate immune responses. Stimulated by interferon-gamma (IFN-gamma) to express HLA-DR, neutrophils acquire accessory cell functions for superantigen-mediated T cell activation. In vitro HLA-DR induction on neutrophils varies in a functionally relevant way as levels of MHC class II expression and magnitude of neutrophil induced T cell responses are correlated functions. The aim of this study was to assess whether IFN-gamma induces HLA-DR on human neutrophils in a donor dependent fashion in vivo and to define regulatory events operative in MHC class II expression of neutrophils. In vivo administration of rhIFN-gamma in 55 patients with renal cell carcinoma resulted in a varying increase of HLA-DR on neutrophils. By setting a cut-off for response at>10% HLA-DR positive neutrophils, HLA-DR responders (51%) were as frequent as nonresponders (49%). In vivo kinetic studies revealed a peak expression of HLA-DR on neutrophils 48 h after rhIFN-gamma application, while nonresponders remained HLA-DR negative over a 72-h period. In vitro IFN-gamma stimulated neutrophils recapitulated the response profiles observed in vivo. No differences in IFN-gamma dependent CD64 and invariant chain expression, and IFN-gamma serum levels were observed among the response subgroups. HLA-DR mRNA was detected in neutrophils from rhIFN-gamma treated responders and nonresponders, HLA-DR protein solely in lysates of responder neutrophils. IFN-gamma stimulated HLA-DR expression on neutrophils is subject to donor dependent variations in vivo, which result from rather post-transcriptional than transcriptional regulation. Due to their abundance in inflammatory reactions heterogeneous HLA-DR expression by neutrophils could determine the outcome of superantigen-driven diseases.

Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: In patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), prognostic scores may identify those with a poor prognosis or even those with a clear survival benefit. The Child-Pugh score (CPS) is well established but several drawbacks have led to development of the model of end stage liver disease (MELD). AIM: The aim of the study was to compare the predictive power of CPS and MELD, to validate the original MELD formula, and to assess the predictive value of the determinants used in the two prognostic scores outside of a study setting. PATIENTS: A total of 501 patients underwent elective TIPS placement and 475 patients fulfilled the inclusion criteria. METHODS: Data of all patients undergoing elective TIPS in one university hospital and four community hospitals in Vienna, Austria, between 1991 and 2001, were analysed retrospectively. The main statistical tests were Cox proportional hazards regression model, the log rank test, Kaplan-Meier analysis, and concordance c statistics. RESULTS: Median follow up was 5.2 years and median survival was 4.6 years. During follow up, 230 patients died, 75 within three months after TIPS placement. In stepwise proportional hazards analyses, independent predictors of death were creatinine level, bilirubin level, age, and refractory ascites. MELD was better in predicting survival in a stepwise Cox model but both scores were equally predictive in c statistics for one month, three month, and one year survival. Renal function was the strongest independent predictor of survival. CONCLUSIONS: Although MELD was the primary predictor of overall survival in multivariate analysis, c statistics showed that both scores can be used for patients undergoing TIPS with equal accuracy. For assessing prognosis in patients undergoing TIPS implantation, there seems little reason to replace the well established Child-Pugh score.

Exocrine pancreatic dysfunction in sepsis.

BACKGROUND: Sepsis in critical illness is associated with the progressive failure of multiple organs. This study aims to establish a correlation between the severity of sepsis and exocrine pancreatic dysfunction. MATERIALS AND METHODS: In a prospective cohort study pancreatic exocrine function was tested by means of a secretin-cholecystokinin test in 21 critically ill, mechanically ventilated patients with sepsis according to criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (ACCP/SCCM): 11 patients with shock and 10 patients without shock. Data were compared with seven healthy controls. RESULTS: The volume of duodenal fluid was not statistically different in the three groups. Sepsis patients without shock had significantly reduced content of amylase and chymotrypsin in duodenal juice compared with healthy controls (P < 0.01). Secretion of amylase, chymotrypsin, trypsin (P < 0.01 each) and bicarbonate in duodenal fluid (P < 0.05) was impaired in the septic shock patients when compared with the healthy controls. The content of trypsin was different between sepsis patients and septic shock patients (P < 0.05). Spearman correlation analysis was significant between the amylase secretion and the APACHE III and SOFA scores (P < 0.01). The SOFA score was also related to secretion of trypsin (P < 0.05). In patients on pressor therapy, use of norepinephrine was associated with a significant decrease in bicarbonate secretion (P < 0.05). CONCLUSIONS: Sepsis is associated with secretory pancreatic dysfunction that is worse in septic shock than in sepsis without shock. Impaired exocrine function was significantly correlated to the APACHE III and SOFA scores.