[A 17 year old adolescent with chronic neutropenia, recurrent infections, severe dysphagia and peroneus palsy]. / 17-jähriger Mann mit jahrelanger Neutropenie und Infektneigung, schwerer Dysphagie und Peroneuslähmung.

A 17-year-old German adolescent with a four year history of neutropenia and repeated infections presented with severe dysphagia and progressive right-sided peroneus palsy. In the past four years, extensive medical workup had been performed, and despite conspicuous findings, no diagnosis was made. Finally we diagnosed HIV related CMV esophagitis and HIV associated polyneuropathy. The CMV esophagitis was treated antivirally, and highly active antiretroviral HIV therapy was initiated. The mode of HIV transmission remained obscure until further research revealed a probable nosocomial infection during early childhood in Romania.

Bile synthesis in rat models of inflammatory bowel diseases.

BACKGROUND: A broad spectrum of hepatobiliary disorders are found in patients with inflammatory bowel diseases. The aim of the present work was to study interactions between gut and liver in experimental rat models of colitis and small bowel inflammation. MATERIALS AND METHODS: Colitis was induced either by trinitrobenzene sulphonic acid or dextran sodium sulphate. Small-bowel inflammation was induced by indomethacin. Bile acid secretion, bile acid pool, and cholesterol 7-alpha hydroxylase were studied. Cholesterol 7-alpha hydroxylase protein expression was analysed in the microsomal liver fraction. As portal mediators released form the inflamed gut we measured lipopolysaccharide, tumour necrosis factor-alpha and interleukin-1beta in portal serum. The hepatic inflammatory response was evaluated by binding activity of nuclear factor-kappaB, activator protein-1 and alpha-2-macroglobulin. RESULTS: Increased bile acid secretion, total bile acid content in gut and liver (bile acid pool size), and hepatic cholesterol 7-alpha hydroxylase protein and mRNA levels were found in the two colitis models associated with only a minor hepatic acute phase and cytokine response. In contrast, during indomethacin-induced small-bowel inflammation bile acid secretion, pool size, and cholesterol 7-alpha hydroxylase decreased in parallel to a strong hepatic cytokine and acute phase response. CONCLUSIONS: Colitis without portal cytokine release and acute phase reaction shows an induction of bile acid secretion, pool size, and cholesterol 7-alpha hydroxylase. In contrast, intestinal inflammation after indomethacin treatment is associated with an acute phase response and a repression of bile acid synthesis.

[Noninvasive brush biopsy as an innovative tool for early detection of oral carcinomas]. / Nichtinvasive Bürstenbiopsie als innovative Methode in der Früherkennung des Mundhöhlenkarzinoms.

PURPOSE: The aim of this prospective study was to investigate the diagnostic accuracy of DNA image cytometry in combination with non-invasive brush biopsies taken from suspicious oral lesions. MATERIAL AND METHODS: Cytological diagnoses obtained from 1328 exfoliative smears of 332 different lesions were compared with histology and/or clinical follow-ups of the respective patients. Additionally, nuclear DNA contents were measured after Feulgen restaining using a TV image analysis system. DNA aneuploidy was assumed if abnormal DNA stemlines or cells with DNA content greater than 9c were observed. RESULTS; The sensitivity of our cytological diagnosis in addition to DNA image cytometry on oral smears for the detection of cancer cells was 97.8%, specificity 100%, positive predictive value 100%, and negative predictive value 98.1%. CONCLUSION: The application of DNA image cytometry with DNA aneuploidy as a marker for neoplastic transformation in oral smears secures cytologic diagnosis of carcinomas. Smears from brushings of all visible oral lesions are an easily practicable, cheap, noninvasive, painless, and safe screening method for detection of oral precancerous lesions and squamous cell carcinoma in all stages. We conclude that DNA image cytometry is a very sensitive and highly specific, objective, and reproducible adjuvant tool for identification of neoplastic cells in oral smears.

[82-year old patient with hyperostosis frontalis, prognathism, makroglossia and cutis gyrata. Acromegaly]. / 82-jährige Patientin mit Hyperostosis frontalis, Prognathie, Makroglossie und Cutis gyrata. Akromegalie.

We present a 82 year old female patient with typical acral enlargement. There were no signs of visceromegaly. Magnetic resonance imaging of the pituitary region showed a macroadenoma. Oral glucose tolerance test revealed missing suppression of the Human Growth Hormone (HGH), which could be achieved with a long acting somatostatin analog. A HGH suppressive therapy with a long acting dopamine agonist (Cabergolin) was induced. The patient died one year later following cardiovascular complications.

Randomized, controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C.

BACKGROUND/AIMS: Efficacy and safety of interferon-alpha (IFN-alpha)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C. METHODS: Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-alpha alone or in combination with ribavirin or amantadine were treated with IFN-alpha 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000-1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24. RESULTS: An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 (P<0.001), low viremia (P=0.011) and only one previous antiviral treatment (P=0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-alpha/ribavirin alone (25 versus 18%, P=0.172). CONCLUSIONS: The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-alpha/ribavirin alone, in particular in patients with low baseline viremia.

Lipopolysaccharide represses cholesterol 7-alpha hydroxylase and induces binding activity to the bile acid response element II.

BACKGROUND: Inflammatory states such as hepatitis and sepsis are frequently associated with alterations of bile acid synthesis. These conditions are mediated by bacterial wall products like lipopolysaccharide (LPS). Cholesterol 7-alpha hydroxylase is the rate-limiting enzyme of bile acid synthesis. Hydrophobic bile acids repress cholesterol 7-alpha hydroxylase transcription via binding to the farnesoid X receptor and interaction with the bile acid response element II in the cholesterol 7-alpha hydroxylase promoter. METHODS: We tested the effect of LPS on hepatic expression of cholesterol 7-alpha hydroxylase in C57BL/6 mice and Wistar rats. Further, we analyzed the binding activity of hepatic nuclear extracts to the bile acid response element II and the binding site for farnesoid X receptor heterodimers (ecdysone response element). RESULT: Lipopolysaccharide caused a 100-fold reduction of cholesterol 7-alpha hydroxylase mRNA levels in mice and a 10-fold reduction in rats. Protein levels of cholesterol 7-alpha hydroxylase also decreased in both species. These changes inversely correlated with the increased binding activity of nuclear proteins to the bile acid response element II and the ecdysone response element. CONCLUSION: Lipopolysaccharide-induced repression of cholesterol 7-alpha hydroxylase occurs at the transcriptional level. The underlying mechanism involves an increased binding activity of nuclear proteins to the bile acid response element II and the ecdysone response element. In conclusion, the farnesoid and retinoid X receptors participate in LPS-induced cholesterol 7-alpha hydroxylase repression.

Phenylalanine kinetics in healthy volunteers and liver cirrhotics: implications for the phenylalanine breath test.

Expired 13CO2 recovery from an oral l-[1-13C]phenylalanine ([13C]Phe) dose has been used to quantify liver function. This parameter, however, does not depend solely on liver function but also on total CO2 production, Phe turnover, and initial tracer distribution. Therefore, we evaluated the impact of these factors on breath test values. Nine ethyl-toxic cirrhotic patients and nine control subjects received intravenously 2 mg/kg of [13C]Phe, and breath and blood samples were collected over 4 h. CO2 production was measured by indirect calorimetry. The exhaled 13CO2 enrichments were analyzed by isotope ratio mass spectrometry and the [13C]Phe and l-[1-13C]tyrosine enrichments by gas chromatography-mass spectrometry. The cumulative 13CO2 recovery was significantly lower in cirrhotic patients (7 vs. 12%; P < 0.01), in part due to lower total CO2 production rates. Phe turnover in cirrhotic patients was significantly lower (33 vs. 44 micro mol. kg(-1). h(-1); P < 0.05). When these extrahepatic factors were considered in the calculation of the Phe oxidation rate, the intergroup differences were even more pronounced (3 vs. 7 micro mol. kg(-1). h(-1)) than those for 13CO2 recovery data. Also, the Phe-to-Tyr conversion rate, another indicator of Phe oxidation, was significantly reduced (0.7 vs. 3.0 micro mol. kg(-1). h(-1)).

Comparison of ultrasonic scalpel versus argon-beam and conventional electrocautery for internal thoracic artery dissection.

BACKGROUND: We used an ultrasonic scalpel (USS) and an argon beam coagulator (ABC) to test their effectiveness and feasibility in comparison to conventional electrocautery for Internal Thoracic Artery (ITA) takedown, time for takedown, number of clips, thermal impact, along with morphological integrity assessed by histology. PATIENTS AND METHODS: Ninety-three patients undergoing elective coronary bypass surgery were prospectively randomized into three groups. In thirty-one patients, either an ultrasonic scalpel (USS, group A), an argon-beam coagulator (ABC, group B) or conventional electrocautery (CEC, group C) was used for ITA harvesting. RESULTS: Harvest times for ITA takedown using CEC (16.7 +/- 6 min) was significantly faster compared to ABC (21.6 +/- 8.1 min; p = 0.02) and USS (24.1 +/- 8.1 min; p < 0.001). There was no significant difference comparing harvest times of USS and ABC (p = 0.1). The number of hemostatic clips used was significantly lower when using USS (5.5 +/- 4.6 clips) compared to both CEC (16.6 +/- 6.2 clips; p < 0.001) and ABC (20.4 +/- 6.5 clips; p < 0.001) and significantly lower using CEC compared to ABC (p < 0.007). There were no significant differences in bleeding points within the tissue bed among the groups (ABC 11/31 patients, CEC 11/31 patients and USS 12/31 patients). CONCLUSION: This study demonstrates that dissection of the ITA pedicle can be safely done with USS, ABC, and CEC. However, USS is associated with less hemostatic clip demand but prolonged harvest time compared it to ABC and CEC; histological assessment revealed no significant difference when comparing groups and equipment used. A variety in design of the hooks may probably ease ultracision practicability.

Oxidized low-density lipoproteins bind to the scavenger receptor, CD36, of hepatic stellate cells and stimulate extracellular matrix synthesis.

Cumulating evidence suggests that oxidative stress resulting in lipid peroxidation and protein modification is involved in the pathogenesis of chronic liver injury and fibrogenesis. We investigated the effects of oxidized low-density lipoproteins (oxLDL) on collagen and fibronectin synthesis of cultured human and rat hepatic stellate cells (HSC). As shown on protein and mRNA levels, oxLDL dose-dependently stimulated the synthesis of collagen types I and III and fibronectin of cultured HSC. The effect was biphasic, with a maximum between 5 and 25 microg/mL oxLDL (c-fibronectin concentration in HSC supernatants increased 3.9-fold; collagen type I increased 4-fold). Higher oxLDL concentrations were cytotoxic. LDL modified with malondialdehyde (MDA) was not toxic, but stimulated extracellular matrix synthesis as well. As demonstrated by immunofluorescence microscopy (double staining of CD36 and iso-alpha-smooth muscle actin [iso-alpha-sm actin]), immunoblot, and reverse-transcription polymerase chain reaction (RT-PCR), respectively, cultured human HSC express the oxLDL receptor, CD36 (glycoprotein IIIb). Colocalization of CD36 and iso-alpha-sm actin on sinusoidal lining cells was further demonstrated using sections of human fibrotic liver. Preincubation of cultured human HSC with the monoclonal antibody, OKM5, known to block CD36-mediated oxLDL uptake, resulted in a reduction of the oxLDL-stimulated collagen type I synthesis by 56%. In summary, our results demonstrate that low concentrations of modified lipoproteins (oxLDL and MDA-LDL) represent fibrogenic mediators that bind to CD36 and stimulate matrix synthesis of HSC.

Cytologic and DNA-cytometric early diagnosis of oral cancer.

OBJECTIVE: The aim of this prospective study was to report on the diagnostic accuracy of conventional oral exfoliative cytology taken from white-spotted, ulcerated or other suspicious oral lesions in our clinic. In addition we checked DNA-image cytometry as an adjuvant diagnostic tool. Our hypothesis is that DNA-aneuploidy is a sensitive and specific marker for the early identification of tumor cells in oral brushings. STUDY DESIGN: 251 cytological diagnoses obtained from exfoliative smears of 181 patients from macroscopically suspicious lesions of the oral mucosa and from clinically seemingly benign oral lesions which were excised for establishing histological diagnoses were compared with histological and/or clinical follow-ups of the respective patients. Additionally nuclear DNA-contents were measured after Feulgen restaining using a TV image analysis system. RESULTS: Sensitivity of our cytological diagnosis on oral smears for the detection of cancer cells was 94.6%, specificity 99.5%, positive predictive value 98.1% and negative predictive value 98.5%. DNA-aneuploidy was assumed if abnormal DNA-stemlines or cells with DNA-content greater 9c were observed. On this basis the prevalence of DNA-aneuploidy in smears of oral squamous cell carcinomas in situ or invasive carcinomas was 96.4%. Sensitivity of DNA-aneuploidy in oral smears for the detection of cancer cells was 96.4%, specificity 100%, positive predictive value 100% and negative 99.0%. The combination of both techniques increased the sensitivity to 98.2%, specificity to 100%, positive predictive value to 100% and negative to 99.5%. CONCLUSIONS: Brush cytology of all visible oral lesions, if they are clinically considered as suspicious for cancer, are an easily practicable, cheap, non-invasive, painless, safe and accurate screening method for detection of oral precancerous lesions, carcinoma in situ or invasive squamous cell carcinoma in all stages. We conclude that DNA-image cytometry is a very sensitive, highly specific and objective adjuvant tool for the early identification of neoplastic epithelial cells in oral smears.

Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells.

The aim of this study was to identify fibrogenic mediators stimulating activation, proliferation, and/or matrix synthesis of rat pancreatic stellate cells (PSC). PSC were isolated from the pancreas of normal Wistar rats and from rats with cerulein pancreatitis. Cell activation was demonstrated by immunofluorescence microscopy of smooth muscle alpha-actin (SMA) and real-time quantitative RT-PCR of SMA, fibronectin, and transforming growth factor (TGF)-beta(1). Proliferation was measured by bromodeoxyuridine incorporation. Matrix synthesis was demonstrated on the protein and mRNA level. Within a few days in primary culture, PSC changed their phenotype from fat-storing to SMA-positive myofibroblast-like cells expressing platelet-derived growth factor (PDGF) alpha- and PDGF beta-receptors. TGF-beta(1) and tumor necrosis factor (TNF)-alpha accelerated the change in the cells' phenotype. Addition of 50 ng/ml PDGF and 5 ng/ml basic fibroblast growth factor (bFGF) to cultured PSC significantly stimulated cell proliferation (4.37 +/- 0.49- and 2.96 +/- 0.39-fold of control). Fibronectin synthesis calculated on the basis of DNA was stimulated by 5 ng/ml bFGF (3.44 +/- 1.13-fold), 5 ng/ml TGF-beta(1) (2.46 +/- 0.89-fold), 20 ng/ml PDGF (2.27 +/- 0.68-fold), and 50 ng/ml TGF-alpha (1.87 +/- 0.19-fold). As shown by RT-PCR, PSC express predominantly the splice variant EIII-A of fibronectin. Immunofluorescence microscopy and Northern blot confirmed that in particular bFGF and TGF-beta(1) stimulated the synthesis of fibronectin and collagens type I and III. In conclusion, our data demonstrate that 1) TGF-beta(1) and TNF-alpha accelerate the change in the cell phenotype, 2) PDGF represents the most effective mitogen, and 3) bFGF, TGF-beta(1), PDGF, and, to a lesser extent, TGF-alpha stimulate extracellular matrix synthesis of cultured rat PSC.

[Value of magnetic resonance tomography for interventions in the ENT specialty]. / Die Nutzung der Magnetresonanztomographie bei Interventionen auf dem Gebiet der HNO-Heilkunde.

PURPOSE: Presentation of new concepts and applications of MR-guided head and neck surgery are presented. Examples of diagnostic and therapeutic procedures such as evaluation of transseptal tumor biopsies, placement of afterloading catheters for brachytherapy, and microscopic surgery of paranasal sinuses in the open MRI are discussed. MATERIAL AND METHODS: 24 MRI-guided ENT-procedures (14 transsphenoidal biopsies, one transnasal biopsy, 6 placements of brachytherapy catheters, and 3 operations of the paranasal sinuses) were performed in an open 0.5 T MR system. RESULTS: Localisation and/or extension of all lesions as well as the placement of biopsy needles or catheters were determined with great precision during the interventions. CONCLUSIONS: Surgical risk and postoperative morbidity are significantly reduced in MR-guided surgery of the petroclival region and the region of head and neck compared to other, conventional methods. Thus, interventional MRI-guidance optimizes minimal invasive surgery and catheter placement in difficult anatomical regions like the petroclival region.

Ability of MR cholangiography to reveal stent position and luminal diameter in patients with biliary endoprostheses: in vitro measurements and in vivo results in 30 patients.

OBJECTIVE: Our goal was to evaluate the ability of MR cholangiography to show stent position and luminal diameter in patients with biliary endoprostheses. MATERIALS AND METHODS: Susceptibility artifacts were evaluated in vitro in three different stent systems (cobalt alloy-based, nitinol-based, and polyethylene) using two breath-hold sequences (rapid acquisition with relaxation enhancement, half-Fourier acquisition single-shot turbo spin echo) on a 1.5-T MR imaging system. The size of the stent-related artifact was measured, and the relative stent lumen was calculated. In vivo stent position and patency were determined in 30 patients (10 cobalt alloy-based stents, five nitinol-based stents, and 15 polyethylene stents). RESULTS: In vitro, the susceptibility artifact of the cobalt stent caused complete obliteration of the stent lumen. The relative stent lumens of the nitinol-based and polyethylene stents were 38-50% and 67-100%, respectively. In vivo, all stents were patent at the time of imaging. The position of the cobalt alloy-based stent could be determined in nine of 10 patients, but stent patency could not be evaluated. Stent position of nitinol stents could not be adequately evaluated in any of the five patients, and internal stent diameter could be visualized in only one patient. In nine of 15 patients, the fluid column within the implanted polyethylene stent was seen on MR cholangiography. CONCLUSION: The internal stent lumen could be visualized in most patients with an indwelling polyethylene stent, but not in patients with cobalt alloy- or nitinol-based stents.

Inhibition of nitric oxide synthesis by aminoguanidine increases intestinal damage in the acute phase of rat TNB-colitis.

The role of nitric oxide (NO) in the pathophysiology of inflammatory bowel diseases (IBD) is controversially discussed. The aim of the present study was to investigate the role of NO inhibition in the acute phase of rat 2,4,6-trinitrobenzenesulphonic acid (TNB)-colitis. To inhibit NO synthesis we used aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide synthase (iNOS). TNB-colitis was induced in rats with and without pretreatment with AG (200 mg kg-1 body weight in the drinking water). The severity of colitis was observed over a period of 7 days. On days 1 and 2, AG reduced concentrations of plasma nitrate and nitrite as well as of portal 6-keto-prostaglandin 1alpha. AG pretreatment increased colonic damage and inflammatory response, assessed by colonic myeloperoxidase and serum lactate dehydrogenase activity, macroscopic damage score, tumour necrosis factor-alpha concentration in stool and colonic glutathione content. The AG-treated group showed a higher and prolonged nuclear factor kappaB (NF-kappaB)/Rel binding activity in the colon. We conclude that NOS inhibition by AG is not beneficial in acute intestinal inflammation. With regard to appropriate therapeutic strategies, NF-kappaB/Rel activation might be a more suitable target.

Modulation of endogenous nitric oxide synthase in experimental acute pancreatitis: role of anti-ICAM-1 and oxygen free radical scavengers.

OBJECTIVE: To evaluate, in an experimental model of acute pancreatitis, the impact of nitric oxide on the disease process and the interaction between nitric oxide and oxygen free radicals. SUMMARY BACKGROUND DATA: Nitric oxide and oxygen free radicals are involved in the pathophysiology of acute pancreatitis. It is well established that oxygen free radicals play an important role in the development of pancreatic cell damage and remote organ failure, but the impact of nitric oxide on the disease process and the interactions between the two radical species remain controversial. METHODS: Necrotizing pancreatitis (NP) was induced in Wistar rats by intraductal sodium taurocholate infusion after pretreatment with isotonic saline (NP-S), superoxide dismutase/catalase (NP-SOD/CAT), or an anti-ICAM-1 antibody (aICAM-1). Sham-operated rats received isotonic saline (SHX). After an observation period of 5 minutes and 24 hours, the pancreas was removed for microscopy, glutathione, and myeloperoxidase (MPO) analysis. The inducible NO synthase (NOS-2) was detected by Western blotting or RT-PCR. Serum was analyzed for nitrite/nitrate (NO2-/NO3-) and S-nitrosothioles (RSNO), while plasma was used to assay for trypsinogen activation peptides (TAP). RESULTS: NP-S animals showed a significant decrease in GSH levels after NP-induction as compared with animals under therapy. Increased MPO levels in the NP-S group were significantly reduced by aICAM-1 while SOD/CAT injection showed no changes. Serum NO-derivatives peaked at 12 hours while TAP levels had a maximum at 6 hours after NP induction, and were lower after aICAM-1 application SOD/CAT treatment increased both parameters. Extended acinar cell damage and inflammatory infiltrate developed in NP-S animals and was significantly improved by SOD/CAT and aICAM-1 treatment. RT-PCR and Western-blot analysis revealed NOS-2 expression in the NP-S group, which was reduced by radical scavengers and aICAM-1. CONCLUSION: Enhanced nitric oxide synthase expression and increased nitric oxide derivatives are found during severe acute pancreatitis. Oxygen free radicals and neutrophils seem to be potent and important regulation mechanisms for nitric oxide synthase activity and nitric oxide-mediated toxicity but imply only a secondary role for nitric oxide in the local pathologic mechanism of this disease.

Transnasal and transsphenoidal MRI-guided biopsies of petroclival tumors.

Magnetic resonance imaging (MRI) allows excellent tissue characterization in the area of the petroclival region and can depict lesions not visualized with ultrasound or computed tomography (CT). The aim of this study was to demonstrate the clinical feasibility and utility of an interactive MR-guidance system to target and biopsy tumors in the petroclival region. MRI-guided biopsies of 10 patients with tumors in the clivus and petrous apex were performed in an open 0.5-T MR system. Lesions were targeted through a transsphenoidal or transnasal approach. Imaging during biopsies was achieved by a combination of standard and interactive mode. T1-weighted spin-echo, T2-weighted fast spin-echo (FSE), and three-dimensional T1-weighted gradient-echo (GRE) scans (standard mode) were selected to provide optimal tissue characterization for both the lesion and surrounding structures and varied according to the anatomic site. For interactive imaging, T1-weighted GRE and T2-weighted FSE sequences were used. We performed MRI-guided transsphenoidal biopsies in 10 patients who had lesions identified by CT (n = 5) and/or MRI (n = 10). The indications for biopsies were to differentiate between suspected malignant processes (n = 4 ) and benign processes (n = 6). Lesions adjacent to structures like the internal carotid artery were accurately targeted in particular. All biopsies were performed successfully and were the basis for selection of further treatment. No complications occurred during the procedures. An open MR system allows interactive control of biopsies in the area of the petroclival region, providing maximum patient safety and diagnostic accuracy not possible in other systems. The advantages of MRI tissue characterization are combined with an interactive, one-step method of localization and targeting, as well as tissue sampling. J. Magn. Reson. Imaging 2001;13:3-11.

Effects of hepatocellular iron imbalance on nitric oxide and reactive oxygen intermediates production in a model of sepsis.

BACKGROUND/AIMS: In mammals iron homeostasis is most important, as imbalance of iron such as iron overload may lead to severe diseases. Recently, it has been shown that the iron regulatory protein-1 is partially controlled by nitric oxide and reactive oxygen intermediates, molecules frequently seen in inflammatory events. The aim of the present study was to investigate the effects of impaired iron homeostasis on the interaction of nitric oxide, and reactive oxygen intermediate formation in hepatocytes in a model of acute inflammation. METHODS: Hepatocytes isolated from Corynebacterium parvum (C parvum)-injected rats were used to examine the formation of nitrogen and oxygen intermediates by iron deprivation and iron overload in the presence of lipopolysaccharide. In addition, we investigated the RNA binding and aconitase activity of iron regulatory protein-1. RESULTS: In the present study we show that iron overload in lipopolysaccharide-treated C. parvum-primed hepatocytes downregulated the RNA binding of iron regulatory protein-1 and aconitase activity. Subsequently, we observed a reduced formation of nitrite/nitrate and S-nitrosothiols but an increased production of reactive oxygen species, and hepatocellular damage. Moreover, the addition of iron to cell cultures caused a further increase in cellular damage, a drop in the cellular glutathione pool, and an increase in peroxynitrite and hydroxyl-like radicals. In contrast, addition of deferoxamine (an iron chelator) to lipopolysaccharide-treated C. parvum-primed hepatocytes protected cells by stabilizing the GSH content, maintaining the nitric oxide formation, and by reducing Fenton oxidants. CONCLUSIONS: Our results show that the antioxidative effects of iron chelators prevent the formation of toxic Fenton oxidants in severe inflammatory events, which should be considered in the treatment of disorders characterized by an iron imbalance.

Minimally invasive saphenous vein harvesting techniques: morphology and postoperative outcome.

BACKGROUND: Conventional saphenous vein harvest is associated with numerous complications, which may be reduced by minimally invasive vein-harvesting techniques. The integrity of the venous endothelium must be guaranteed before using new saphenous vein harvesting techniques. This short-term study compared the clinical outcome of two minimally invasive techniques with the conventional technique, and compared morphology as documented by light and electron microscopy. METHODS: Ninety-two patients were prospectively randomized into three groups. Two different minimally invasive techniques of greater saphenous vein harvesting were used in sixty-two patients. One used a video-assisted dissector (group A, n = 31), and one used a light-coupled retractor (group B, n = 31). Thirty patients were treated by the conventional technique (group C). RESULTS: Incision lengths were 7.6+/-2.1 cm in group A and 9.3+/-3.2 cm in group B, as compared with 38.9+/-8.7 cm in the conventional group. Harvesting time was prolonged by a mean of 26% when using a minimally invasive technique. Conversion rate to the open technique was 3 of 31 (9.3%) in group A and 2 of 31 (6.2%) in group B. No wound complications were noted in group A, but one wound inflammation was seen in group B; only a mild hematoma was seen in both groups. Edge necrosis, wound separation and inflammation were noted in the conventional group. Light and electron microscopy revealed no significant denudation of the endothelial layer in groups A and B as compared with group C. CONCLUSIONS: These data show an excellent postoperative result when using the minimally invasive technique as compared with the conventional group. The safety of the technique is demonstrated by the preservation of endothelial integrity.

[The value of spiral CT in the staging of carcinomas of the oral cavity and of the oro- and hypopharynx]. / Wert der Spiral-CT im Staging von Karzinomen der Mundhöhle und des Oro- und Hypopharynx.

PURPOSE: To compare spiral and conventional CT in the staging of carcinomas of the oral cavity, the oropharynx and hypopharynx. METHOD: Retrospectively 101 conventional CTs and prospectively 107 spiral CTs were analyzed regarding to correct T and N staging. CT results were compared with histological staging. RESULTS: In conventional CT, there were correctly staged 85% of T stages (T1 62%, T2 74%, T3 81%, T4 94%) and 85% of N stages (N0 79%, N1 71%, N2 89%, N3 94%). Spiral CT showed correct results in 84% of T stages (T1 67%, T2 74%, T3 88%, T4 95%) and in 86% of N stages (N0 82%, N1 78%, N2 90%, N3 93%). No statistically significant differences could be found between both CT methods. CONCLUSION: In spite of the tendency of improved diagnosis of T1, N0 and N1 stages no clear improvement in the staging of carcinomas of the oral cavity, the oropharynx and hypopharynx could be expected by spiral CT.

Disturbed bile secretion and cytochrome P450 function during the acute state of experimental colitis in rats.

BACKGROUND/AIMS: A variety of hepatobiliary abnormalities has been described in patients with inflammatory bowel diseases. However, the pathophysiological mechanisms leading to these liver alterations are poorly understood. The aim of the present study was to investigate parameters of liver function in a trinitrobenzenesulfonic acid (TNB)-induced rat colitis model. METHODS: Glucose output, bile acid secretion, bile acid uptake, and the cytochrome P-450 metabolic capacity during TNB-colitis were studied in the perfused liver model. Furthermore, hepatic bile acid- and glycogen content was measured. To evaluate the inflammatory response in the colon and liver, NF-kappaB/Rel was quantified by electrophoretic mobility shift assays. As an NF-kappaB/Rel regulated gene the inducible NO-synthase (NOS2) was evaluated by Western blot analysis. As possible mediators released from the inflamed colon into the portal vein, endotoxin and the stable metabolite of prostaglandin I2 (6-keto-prostaglandin-F1alpha) were determined. RESULTS: Glucose output, bile acid secretion, bile acid uptake, and cytochrome P-450 metabolic capacity decreased on the first and second day of TNB-colitis. Hepatic bile acid content increased at day 14 of colitis. Glycogen content was reduced, most likely due to an inadequate chow intake of these animals. A low level of portal endotoxin was detectable during the first 2 days of colitis. In addition, 6-keto-prostaglandin-F1alpha was clearly increased in portal blood. NF-kappaB/Rel binding activity and inducible NOS2 were strongly positive in the colon during colitis. Although low levels of portal endotoxin were measured during the first 2 days of colitis, no significant NF-kappaB/Rel activity and NOS2 induction were detected in the liver. CONCLUSION: Our results indicate that during the acute state of the TNB-colitis, bile acid secretion and cytochrome P-450 function are disturbed in the absence of distinct inflammatory changes in the liver.