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G Ramadori

Publications and source records attributed to G Ramadori.

At least 19 recordsLinked to original sources
PubMed2006

[Successful management of malaria tropica with 50% parasitaemia].

HISTORY: A 52-year-old woman was hospitalized with fever after a 3-week stay in tropical Kenya. Prophylaxis against malaria had been carried out with chloroquine. DIAGNOSIS: Falciparum malaria with 28% parasitaemia at first examination, rising to 50% after 3 hours. TREATMENT AND COURSE: Treatment with quinine dihydrochloride i.v. was initiated immediately after diagnosis. In addition, in view of increasing parasitemia of up to 50%, a partial exchange blood transfusion was carried out. No clinical signs of organ damage caused by malaria were observed. Because of a drop in blood pressure the patient needed catecholamine treatment for a short time. After decrease of the parasitemia the patient rapidly recovered and complete cure was achieved. CONCLUSION: Despite extremely high parasitemia the clinical signs were unusually mild. Standard treatment for severe malaria is intravenous administration of quinine. However, this drug is no longer sold in Germany, so that difficulty in obtaining it must be expected. A stockpiling of quinine is recommended for hospitals treating patients with malaria. Transfusion may improve outcome and must be considered if parasite counts are high or if there are clinical signs of malaria complications.

Animals↗
PubMed2006

Characterization of gene expression profile in rat Kupffer cells stimulated with IFN-alpha or IFN-gamma.

BACKGROUND AND AIM: Kupffer cells are intrasinusoidal space located macrophages with phagocytic capacity. Interferons are cytokines with antiviral, antiproliferative and immunomodulatory activities which may influence the activity of Kupffer cells. Aim of this study was to evaluate Kupffer cell gene expression after interferon-alpha or interferon-gamma stimulation in order to investigate a link between these cytokines and macrophage activation. METHODS: Rat Kupffer cells were cultured for 24 h and divided into three groups: unstimulated; stimulated with interferon-alpha and stimulated with interferon-gamma. After 8 h stimulation total RNA was extracted and processed according to Affymetrix protocols and hybridised on R34A microarray gene set. Data analyses was performed using Microarray Analysis Suite 5.0 software. Genes showing remarkably different expression in microarray analysis were confirmed by real-time PCR. RESULTS: Nearly 4000 out of the 8800 genes represented in the array were expressed by Kupffer cells. Among these, interferon-alpha up-regulates 91 genes by over two-fold (antiviral, antigen processing and presentation, and tumour suppressor/proapoptotic genes) and down-regulates 72 genes by 50% or more. Interferon-gamma up-regulates 70 genes by over two-fold and down-regulates 78 genes by 50% or more. Most of the genes induced by interferon-alpha are also induced by interferon-gamma. Down-regulated genes include growth factors and genes involved in cell cycle/proliferation. Real-time PCR confirms the results of the array. CONCLUSION: Interferons directly target rat Kupffer cells and are involved in the regulation of a wide variety of genes. Their expression profile shed light onto molecular mechanism of Kupffer cells activation in specific pathways such as antiviral and antitumour processes.

Animals↗
PubMed2005

Gastrointestinal stromal tumor (GIST) -- single center experience of prolonged treatment with imatinib.

BACKGROUND: The tyrosine kinase inhibitor imatinib has been introduced into the treatment of gastrointestinal stromal tumors (GIST). Here we report our results of prolonged treatment in comparison to a similar group of GIST patients who had died before imatinib became available. METHODS: Fourteen patients with recurrent or metastatic GIST were treated with imatinib. Clinical data and tumor samples of ten patients from the pre-imatinib era were available for comparison. Comparative genomic hybridisation (CGH) was performed on tumors to identify changes that may predict response to treatment. RESULTS: Fourteen patients were treated, mean treatment time 22.3 months (1 non-response, 2 progression after initial response, 2 stable diseases, 8 partial responses, 1 complete response). Adverse side effects were mild in general. Survival was higher in the treated group (41.1 months vs. 34.8 months in the historical group). Eleven treated patients are alive. CGH analysis showed comparable numbers of chromosomal aberations in both groups. CONCLUSION: Prolonged treatment with imatinib is safe and effective in patients with recurrent or metastatic GIST.

Adult↗
PubMed2005

[Esophageal carcinoma -- current status in diagnosis and therapy].

Esophageal carcinoma is characterized by an increasing incidence in the last 15 years whereas the prognosis still remains almost invariably poor. The therapy of choice is still deemed to be surgical resection including extended lymphadenectomy which is accompanied by considerable amounts of peri- and postoperative complications and only rare long-time survival. Precursor lesions and early stage cancers are therefore increasingly often treated by local ablative procedures including mucosectomy, which demonstrates promising results. In advanced tumor stages definitive chemoradiation provided long-term survival equivalent to that in contemporary surgical series and thus represents another alternative to tumor resection. This review points out the epidemiology, aetiology, staging and consequences in therapy for esophageal carcinoma considering current points of view.

Adenocarcinoma↗
PubMed2005

Fasting hyperglucagonemia in patients with transjugular intrahepatic portosystemic shunts (TIPS).

BACKGROUND: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). METHODS: Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). RESULTS: Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. CONCLUSION: In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.

Adult↗
PubMed2005

Nonsurgical treatment of the primary tumor in four consecutive cases of metastasized colorectal carcinoma.

BACKGROUND AND STUDY AIMS: Surgical resection of the primary tumor is standard treatment in stage IV colorectal cancer, but palliative surgery is associated with high morbidity and mortality and with uncertain benefit. The wisdom of surgical resection of asymptomatic or oligosymptomatic primary tumors is therefore questionable. By studying a small series of such patients, we aimed to assess whether endoscopic techniques can offer an effective alternative form of nonsurgical palliative treatment for the prevention of local complications caused by a primary colorectal tumor. PATIENTS AND METHODS: We treated four consecutive patients who had stage IV colorectal cancer by endoscopic tumor debulking, either using a standard polypectomy snare technique alone or by argon plasma coagulation ablation followed by snare debulking of the primary tumor. RESULTS: Palliation was achieved in all patients, demonstrated by regression of the primary tumor and absence of symptoms related to the colonic tumor during the observation period of up to 24 months. No procedure-associated complications were observed and it was possible to commence systemic chemotherapy immediately after the endoscopic treatment in all four patients. CONCLUSIONS: We believe that surgical resection of the primary tumor is not appropriate in all patients with stage IV colorectal cancer, and that this form of treatment should be reserved for patients with signs of complete obstruction in whom local ablative procedures are not possible. Simple endoscopic techniques for treatment of the primary tumor, in conjunction with systemic chemotherapy, may be the most suitable form of management for patients with stage IV colorectal tumors.

Adenocarcinoma↗
PubMed2004

The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium.

Prox1 is a transcription factor with two highly conserved domains, a homeobox and a prospero domain. It has been shown that Prox1 knock-out mice die during early embryonic stages and display a rudimentary liver. We have studied the expression of Prox1 at RNA and protein levels in chick, rat, mouse and human liver and in transformed and non-transformed hepatic cell lines. Prox1 is expressed in early embryonic hepatoblasts and is still expressed in adult hepatocytes. Prox1 protein is located in the nuclei of hepatoblasts, which grow into the neighboring embryonic mesenchyme. The expression pattern in chick, mouse, rat and human embryos is highly conserved. Besides albumin and alpha-fetal protein, Prox1 belongs to the earliest markers of the developing liver. In adult liver, Prox1 is expressed in hepatocytes but is absent from bile duct epithelial and non-parenchymal cells (Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells and myofibroblasts). Isolated primary hepatocytes and hepatoma cell lines (HepG2, Hep3B) are Prox1 positive, whereas the immortalized murine liver cell-line MMH, which constitutively expresses the receptor c-met, is Prox1 negative. Transfection of MMH with Prox1 cDNA increases the expression level significantly as compared to control transfectants. In HepG2 and Hep3B, the Prox1 levels are even up to 100 times higher. Our studies show that Prox1 is a highly conserved transcription factor, expressed in hepatocytes from the earliest stages of development into adulthood and over-expressed in hepatoma cell lines. Its absence from bile duct epithelial cells suggests a function for the specification of hepatoblasts into hepatocytes. The genes controlled by Prox1 need to be studied in the future.

Animals↗
PubMed2004

Glucocorticoid receptor expression in inflammatory bowel disease: evidence for a mucosal down-regulation in steroid-unresponsive ulcerative colitis.

BACKGROUND: Glucocorticoids (GC) play a major role in the attenuation of inflammation. Glucocorticoid receptor (GR) expression is an important determinant of steroid sensitivity. AIMS: To investigate whether GR mRNA expression is altered in inflammatory bowel disease, and whether GR mRNA expression correlates with disease activity and may predict response to GC therapy. METHODS: Mucosal biopsies were taken from 33 patients with ulcerative colitis, 21 with Crohn's disease and 11 controls. Peripheral blood mononuclear cells were isolated from 24 ulcerative colitis and 18 Crohn's disease patients and 11 controls. GR mRNA was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and correlated to endoscopic findings, clinical activity and outcome of GC therapy. In a subset of subjects GR localisation was shown by immunohistochemistry. RESULTS: In patients with inflammatory bowel disease GR expression was not different from controls. However, GR was decreased in biopsies from ulcerative colitis patients with impaired GC response. The inhibitory subtype GRbeta was expressed 100-1000 times lower than GRalpha. GR immunoreactivity was identified in immune and epithelial cells except for colonic crypts. CONCLUSION: In inflammatory bowel disease systemic and mucosal GR mRNA expression is not altered. However, in ulcerative colitis patients, low mucosal GR expression may predict the outcome of GC therapy. The low expression of GRbeta challenges its role in steroid refractoriness in inflammatory bowel disease.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

Ultrasound-guided laser interstitial thermo therapy for treatment of non-resectable primary and secondary liver tumours--a feasibility study.

AIM: Therapeutic options for primary and secondary liver tumours not suitable for resection or transplantation are limited. In this palliative situation, the scope of ablative therapeutic procedures has improved. Laser interstitial thermotherapy is a minimal invasive procedure for local tumour destruction within solid organs. This pilot study reports initial clinical experience using ultrasound-guided percutaneous laser interstitial thermotherapy. METHODS: Sixty patients between the ages of 34 and 78 years with non-resectable primary and secondary liver tumours were treated palliatively with Nd:YAG laser interstitial thermotherapy. High resolution abdominal ultrasound with power duplex was used to control the placement and coagulation procedure. RESULTS: In all cases, sonographic imaging allowed exact placement of the laser probe and verification of thermocoagulation by a resulting hyperechogenic signal enhancement. The maximum diameter of laser-induced destruction measured 5 cm. Ultrasound with power duplex and echo enhancer, CT or MRI scans indicated necrosis of treated tumour lesions. No serious adverse event occurred and 30-day-mortality was zero. CONCLUSIONS: Ultrasound-guided laser interstitial thermotherapy is safe and reliably ablates primary and secondary liver tumours. The combination of high resolution ultrasound and laser therapy facilitates a minimally invasive but elaborate treatment. Besides chemotherapy, this procedure could be a useful palliative treatment to control the mass of liver tumours unsuitable for resection or transplantation.

Adult↗
PubMed2003

The transjugular intrahepatic portosystemic stent-shunt (TIPS) as rescue therapy for complete Budd-Chiari syndrome and portal vein thrombosis.

We present a 40-year-old female patient with epigastric pain, ascites, and progressive liver failure, caused by Budd-Chiari syndrome (BCS) with thrombotic occlusion of the right and middle hepatic veins. As underlying diseases, essential thrombocythemia and resistance to activated protein C (APC) due to heterozygote factor V Leiden were found. Initial therapy with heparin caused thrombocytopenia (HIT) type II culminating in thrombosis of the last patent left hepatic vein and further deterioration of liver function. The decision against a surgical shunt and liver transplantation by our surgeons on the basis of the risks involved, prompted us to insert a transjugular intrahepatic portosystemic stent-shunt (TIPS). There was no measurable flow signal in the doppler sonography of the portal vein presumably due to thrombosis. A further evaluation with magnetic resonance tomography and angiography was impossible due to movement artefacts. TIPS initially served as a diagnostic tool allowing direct angiography-diagnosed thrombosis of the portal vein, the superior mesenteric and the splenic vein respectively. However, insertion of the TIPS shunt and subsequent fragmentation led to an effective hepatic decompression and full recanalisation of the portal vein. In the present case TIPS simultaneously allowed the diagnosis of portal vein thrombosis and served as rescue therapy of complicated Budd-Chiari syndrome. The potential development of HIT type II should be kept in mind when heparin is given, especially to patients with thrombophilia.

Activated Protein C Resistance↗
PubMed2003

TIPS implantation raises leptin levels in patients with liver cirrhosis.

Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74% ethyltoxic men, 50% ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls. In women ascitic-free BMI significantly increased (from 22.8 +/- 4.6 kg/m2 to 23.9 +/- 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 +/- 4.7 vs. 26.7 +/- 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 +/- 8.8 ng/ml vs. 18.6 +/- 14.9; p = 0.009) and in men (7.7 +/- 6.2 ng/ml vs. 12.2 +/- 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 +/- 0.29 vs. 0.73 +/- 0.52; p = 0.017; men 0.28 +/- 0.22 vs. 0.43 +/- 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations. After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.

Adipose Tissue↗
PubMed2003

HFE genotype and parameters of iron metabolism in German first-time blood donors - evidence for an increased transferrin saturation in C282Y heterozygotes.

BACKGROUND: Hemochromatosis is usually inherited in an autosomal recessive mode and associated with missense mutations in the hemochromatosis gene (HFE), an HLA class 1 related gene. However the degree of penetrance is presently matter of debate. METHODS: To elucidate the frequency of HFE mutations in a German population and the relationship between genotype and phenotype, we determined the HFE C282Y and H63D genotypes in 500 first-time blood donors using an allele-specific ligase chain reaction (LCR). Ferritin and transferrin saturation (TS) of all donors found to have at least one mutation were compared to gender- and age-matched controls. RESULTS: The C282Y allele frequency was 46 in 1000 chromosomes (4.6 %). The allele frequency of H63D was 108 in 1000 (10.8 %) chromosomes. We found three persons homozygous for H63D, nine compound heterozygotes and none homozygous for C282Y. TS was elevated in C282Y heterozygotes (p = 0.002) and C282Y/H63D compound heterozygotes (p = 0.04) compared to wild-type controls. Serum ferritin tended to be elevated in compound heterozygotes (p = 0.053). Mean corpuscular volume (MCV) and hemoglobin (MCH) were not different from controls. CONCLUSION: The frequency of HFE mutations in the tested population was comparable to those of other northern European populations. The elevated TS in subjects carrying a single copy of the C282Y mutation suggests that C282Y heterozygosity is associated with an increased intestinal iron absorption and might therefore offer a selection advantage in conditions of iron depletion.

Alleles↗
PubMed2002

Mesenchymal cells in the liver--one cell type or two?

The wall of the liver sinusoid is made of highly specialized cells, the hepatic stellate cells (HSC) which together with the sinusoidal endothelial cells represent a loose barrier to the corpusculate part of the blood flowing through the liver. Quiescent stellate cells (quiescent HSC) store Vitamin A; "activated" stellate cells become involved in the reaction to acute or chronic noxae damaging the liver parenchyma. Activated HSC show increased protein synthesis capacity, increased DNA-synthesis and acquire a myofibroblast-like phenotype. Under similar conditions liver myofibroblasts (MF) of the portal field and of the pericentral area may also become "activated" by increasing protein synthesis, DNA synthesis and cell division. They express the fibulin-2 gene and produce large amounts of IL-6. In contrast to "activated" HSC they do not undergo spontaneous apoptosis in vitro and do not express the CD95-ligand gene. So far no definite prove has been found for a "transdifferentiation" of HSC to myofibroblasts. On the contrary an increasing amount of data support the conviction that HSC and MF represent two similar but not identical cell populations the latter being comparable to those of other organs.

Animals↗