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.

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.

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.

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.

Intestinal metabolism of plasma free fatty acids. Intracellular compartmentation and mechanisms of control.

Fatty acid metabolism in intestinal mucosa has been examined primarily in regard to lipid absorption. Since earlier studies suggested intestinal utilization of plasma free fatty acids (FFA), we investigated mucosal metabolism of plasma FFA in rats. Mucosal radioactivity (1 per cent of administered) was maximal 2 min after i.v. [14C]palmitate. Of mucosal 14C, 42 percent was in water-soluble metabolites, including CO2 and ketoacids, 28 percent in phospholipids, and only 16 per cent in triglycerides. The specific activity of mucosal triglyceride fatty acids (TGFA) was 11 times that of serum TGFA, confirming in situ synthesis. Double isotope experiments showed marked differences in the metabolism of fatty acids entering mucosa simultaneously from lumen and plasma. Whereas luminal fatty acids were chiefly esterified to triglyceride, plasma FFA were preferentially oxidized and incorporated into phospholipids. Crypts did not differ from villi, indicating that intestinal metabolism of plasma FFA is related to their site of entry into epithelial cells. Mucosal metabolism of i.v. [14C]palmitate was minimally affected by glucose administration. However, intraduodenal isocaloric ethanol inhibited mucosal oxidation of FFA by 60 per cent, and increased incorporation into triglycerides nearly twofold. During lipid absorption, mucosal uptake of plasma FFA doubled and incorporation into intestinal lymph triglycerides was increased sixfold. These studies demonstrate an intracellular compartmentation of fatty acids in the intestinal epithelium. In contrast to absorbed luminal fatty acids, plasma FFA in the fasting state are both an energy source and a substrate for the synthesis of tissue phospholipid. The fasting contribution of plasma FFA to mucosal and lymph triglyceride is minimal, but it increases during ethanol administration and fat absorption.

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.

Comparison of functional and structural brain disturbances in Wilson's disease.

We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD.

Wilson's disease: evidence of subgroups derived from clinical findings and brain lesions.

Using exploratory factor analysis, we prospectively investigated neuropsychiatric symptoms and structural brain lesions of 47 patients with proven Wilson's disease and identified three subgroups. The first subgroup clinically exhibited bradykinesia, rigidity, cognitive impairment, and an organic mood syndrome and by MRI showed a dilatation of the third ventricle. The second subgroup was characterized by ataxia, tremor, reduced functional capacity, and focal thalamic lesions. The third subgroup showed dyskinesia, dysarthria, an organic personality syndrome, and focal lesions in the putamen and in the pallidum.

Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study.

BACKGROUND: Extracorporeal photochemotherapy has been proven effective in selected T-cell mediated diseases. AIM: To evaluate the safety and efficacy of extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease by an open, monocentric trial in three phases of 24 weeks each. METHODS: In phase 1 standardized steroid tapering was initiated in patients with a history of steroid-dependent Crohn's disease. Those with a prospectively evaluated maintenance dose of at least 10 mg/day prednisolone continued steroid-withdrawal under the application of extracorporeal photochemotherapy in phase 2. The duration of remission or response was followed during phase 3. Colonic tissue bioptically obtained before and after extracorporeal photochemotherapy was studied by immunofluorescence microscopy for the presence of photoadduct positive cells. RESULTS: Out of 24 patients included in phase 1, 10 entered phase 2 for extracorporeal photochemotherapy. Four subjects achieved remission and four others response. Significant reductions in serum C-reactive protein levels and intestinal permeability were measured, as well as increases in quality of life and plasma adrenocorticotropic hormone levels. No major side-effects were observed. Remission remained stable in three out of four patients during phase 3. In three patients, positive nuclear stainings of photoadducts were detected in colonic mononuclear cells after extracorporeal photochemotherapy. CONCLUSIONS: Extracorporeal photochemotherapy represents a safe steroid-sparing approach in patients with Crohn's disease and is associated with intestinal homing of photopheresed cells.

Surface phenotypes of human peripheral blood mononuclear cells from patients with gastrointestinal carcinoma.

Peripheral blood mononuclear cells (PBMC) from 40 patients with gastrointestinal carcinoma (GIC), 13 patients with primary carcinoma in other localizations(non-GIC), and from 57 apparently healthy donors were isolated by Ficoll-Paque gradient centrifugation. The separated cells were stained with several monoclonal antibodies and subjected to analysis on a fluorescence-activated cell sorter. A decreased percentage of PBMC expressing T cell antigens was noted amongst GIC patients, and was mainly due to a reduction of the Leu 2a subset, thus, leading to an increase in the Leu 3a/Leu 2a ratio from 1.4 to 2.1 Non-GIC patients had decreased numbers of both T helper and suppressor cells. Amongst PBMC from GIC and non-GIC patients a statistically increased percentage of cells expressed LeuM 2 (P less than 0.001), LeuM 3 (P less than 0.001), OKM 1 (P less than 0.005), VEP 9 (P less than 0.001), and HLA-DR (P less than 0.001) antigens compared to healthy controls. The percentage of cells bearing these monocyte/macrophage antigens correlated well with the number of cells having monocyte morphology, stained for non-specific esterase, phagocytosed latex particles, and expressed Fc IgG receptor. Our results demonstrate clearly that tumor-bearing patients have an increased relative number of monocytes. The data suggest that cells of the macrophage lineage may be involved in defense mechanisms and changes of the immune system evoked by various tumors.

Giant benign cystic mesothelioma: a case report and review of literature.

A 28-year-old man was admitted because of weight loss and a huge abdominal mass. The abdominal cavity was filled by a large number of cysts with a maximum diameter of 10 cm as diagnosed by ultrasound and computed tomography. Laparotomy was performed and a 33 kg cystic tumour originating from the peritoneum was resected en bloc. Histopathological work-up showed multiple cysts covered by cubic or flat mesothelial cells with uniform nuclei. The final diagnosis was benign cystic mesothelioma. Twenty-three months after surgical debulking, a follow-up computed tomography scan showed recurrence of the disease. In this report, we describe the characteristics, aetiology and differential diagnosis of this rare lesion.

Prevention of bone mineral loss in patients with Crohn's disease by long-term oral vitamin D supplementation.

OBJECTIVE: To determine whether long-term dietary supplementation with low doses of vitamin D helps to prevent bone loss and the development of osteoporosis or osteomalacia in out-patients with Crohn's disease. DESIGN: A randomized controlled study. SETTING: The out-patient clinic of a tertiary centre (university hospital). PATIENTS: Seventy-five out-patients (31 men and 44 women, aged 16-77 years) with Crohn's disease. INTERVENTIONS: All patients were randomly assigned to receive either an oral supplement of 1000 IU/day vitamin D for 1 year or no supplement. Bone mineral density, assessed in the distal part of the nondominant forearm using single photon absorptiometry, and serum levels of 25-hydroxyvitamin D, assessed using a competitive protein binding assay, were measured before and after the period of dietary supplementation. MAIN OUTCOME MEASURE: Relative change of bone mineral density. RESULTS: Serum levels of 25-hydroxyvitamin D increased in 57% of patients who received a supplement (compared with 37% of control patients). Bone mineral density decreased significantly in control patients [median -7%, interquartile range -12.6-(+0.4%)] but not in patients who received a supplement [median -0.2%, interquartile range -3.8-(+14%); P < 0.005]. Increases in bone mineral density were especially prevalent among patients who received the supplement and had normal serum levels of 25-hydroxyvitamin D (68%), whereas increases occurred in only 18% of patients with low serum levels of 25-hydroxyvitamin D (P = 0.008). Patients without an intestinal resection and receiving the vitamin D supplement had a marginally greater increase in bone mineral content than patients who had undergone a resection (P = 0.05). CONCLUSION: Long-term oral vitamin D supplementation seems to be an efficient means of preventing bone loss in patients with Crohn's disease and could be recommended, especially for patients at high risk of osteoporosis.

Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation.

BACKGROUND AND AIMS: The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics at the time of presentation vary considerably among different parts of the world and over time. The number of patients seen at our institution has increased as compared to a period 20 years earlier. We investigated baseline characteristics of patients with hepatocellular carcinoma such as cirrhosis, hepatitis virus markers, age at presentation and stage of the tumour in an area with low prevalence of viral hepatitis. METHODS: All 245 patients seen at the Department of Gastroenterology and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998 were included in this retrospective study, and 19 different clinical characteristics were studied. RESULTS: The median age at detection of HCC was 63.3 years, and alcoholic liver disease (35.1%) and hepatitis C virus (HCV) infection (36.7%) were the most frequent underlying diseases. Both chronic alcoholism and HCV infection as risk factors were present in 6.9% of the patients. Liver cirrhosis was present in 86.5%. At the time of diagnosis, 43.5% had multi-nodular tumours. Of the remaining patients with a single nodule, only 10% had HCC < or =2 cm. Most of our patients presented at a late stage of the disease (TNM stage 3 29.4%, TNM stage 4 69.7%; Okuda stage 2 65.7%, Okuda stage 3 18.0%). Due to the late stage of the disease at the time of presentation, 145 patients (59.2%) received palliative care only, 24 (9.8%) underwent liver resection, 38 (15.5%) liver transplantation and 38 (15.5%) chemotherapy. CONCLUSIONS: In this large single-centre series of HCC, the dominant contribution of HCV infection and chronic alcohol abuse as the underlying aetiology is documented. Diagnosis is usually made very late as reflected in the high proportion of patients in TNM stages 3 and 4 or Okuda stages 2 and 3. This resulted in a high percentage of patients who received palliative care only and very few who were eligible for treatment modalities with curative potential such as resection and liver transplantation.

The relationship between juxtapapillary duodenal diverticula and biliary stone disease.

OBJECTIVE: To assess the relationship between juxtapapillary duodenal diverticula (JDD) and common bile duct stones and biliary stone disease in general. DESIGN: A retrospective study. METHODS: We analysed 1115 patients who underwent consecutive endoscopic retrograde cholangiopancreatography examinations. The patients were subdivided into three groups: the first group (group I; n = 482) had no biliary stone disease, the second one (group II; n = 329) had common bile duct stones, and the third group (group III; n = 304) had biliary stone disease of the gallbladder but without evidence of common bile duct stones. Additionally, the patients were subdivided into age groups of < 50, 50-59, 60-69, 70-79, and > or = 80 years of age. Logistic regression was applied for statistical analysis. RESULTS: Juxtapapillary duodenal diverticula were diagnosed in 111 (10.0%) patients. The incidence of JDD was 6.9% in group I, 14.3% in group II and 10.2% in group III. Age was the most dominant influence factor for JDD, common bile duct stones, and biliary stone disease (P < 0.0001). Sex was also a factor, female patients having a higher risk for common bile duct stones (P = 0.01) and biliary stone disease (P < 0.0001). After adjustment for age and sex, JDD was found to have a noticeable, but not statistically significant (P = 0.073), influence on common bile duct stones and no influence on biliary stone disease (P = 0.15). CONCLUSION: Our data support only moderately the existence of a relationship, which had been conjectured in a part of the literature, between JDD and common bile duct stones. No noticeable influence on biliary stone disease was found.

No evidence of activated blood coagulation in Crohn's disease.

BACKGROUND: Thromboembolism seems to be a significant and serious complication in Crohn's disease (CD), and multifocal microvascular infarction of the intestinal mucosa may be an important effector mechanism in the pathogenesis of CD. Therefore, it has been hypothesized that an increased activation of the blood coagulation system may favour thromboembolic complications. OBJECTIVES: To assess the activity of blood coagulation as a potential index of thromboembolic risk in CD using thrombin-antithrombin III complex (TAT). DESIGN: Prospective evaluation of TAT. SETTING: Out-patients at the gastroenterological department of a university hospital. PATIENTS: Eighty patients with CD, 47 with inactive (Crohn's disease activity index (CDAI) < 150) and 33 with active disease, and 80 healthy controls were investigated in this study. METHODS: TAT and fibrinogen were used as parameters of blood coagulation. C-reactive protein and orosomucoid were used as serum inflammatory parameters. RESULTS: Fibrinogen was significantly higher in patients with active CD (median 535 mg/dl; interquartile range 402-620 mg/dl) than in patients with inactive CD (357 mg/dl; 300-467 mg/dl) or controls (268 mg/dl; 231-299 mg/dl). Fibrinogen correlated with CDAI, C-reactive protein and orosomucoid. TAT did not show any difference between patients with active CD (3.2 ng/ml; 2.5-4.6 ng/ml), inactive CD (3.0 ng/ml; 2.4-3.9 ng/ml) and controls (3.1 ng/ml; 2.3-3.6 ng/ml). Correspondingly, TAT correlated neither with serum inflammatory parameters and CDAI nor with fibrinogen. CONCLUSION: We could not find evidence of activation of the blood coagulation system as determined by TAT plasma levels in CD, not even in patients with active disease. TAT is not, therefore, a potential index of thromboembolic risk in CD and of microvascular infarction as an effector mechanism in the pathogenesis of CD.

Changes in blood rheology caused by Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) are at increased risk for thromboembolism, and multifocal microvascular infarction has even been suggested as a pathogenetic mechanism in CD. Abnormalities in blood rheology may contribute to the thromboembolism. OBJECTIVES: To assess blood rheology in CD patients. DESIGN: Prospective evaluation of rheological parameters. SETTING: Out-patients at the gastroenterological department of a university hospital. PATIENTS: Thirty-seven patients with inactive CD (Crohn's disease activity index (CDAI) < 150), 31 patients with active CD (CDAI > 150), and 39 control subjects with no CD were included in the study. METHODS: C-reactive protein and orosomucoid were used as serum inflammatory parameters. Fibrinogen, red cell aggregation (low shear, 3/s) and plasma viscosity were used as rheological parameters. RESULTS: Fibrinogen (active CD: median 530 mg/dl (interquartile range 410-630); inactive CD: 377 (316-499); and controls: 246 (220-280)), red cell aggregation (active CD: 9.97 arb. units (8.58-11.77); inactive CD: 9.03 (7.25-10.37); controls: 7.58 (7-8.52)); and plasma viscosity (active CD: 1.82 mPa.s (1.68-1.95); inactive CD: 1.72 (1.65-1.82), controls: 1.61 (1.58-1.64)) were all significantly higher in patients with active and inactive CD than they were in controls. Additionally, fibrinogen was significantly higher in patients with active CD than it was in patients with inactive CD. The rheological parameters correlated with serum inflammatory parameters. CONCLUSION: Changes in blood rheology seem to be associated with inflammatory activity in patients with CD. These changes may be involved in the development of thromboembolism and the pathogenesis of mucosal inflammation, especially in patients with high inflammatory activity.