Biomedical subjects

E G Hahn

Publications and source records attributed to E G Hahn.

At least 127 records · Page 7Linked to original sources

PubMed2001

Changes in quality of life after medical intensive care.

OBJECTIVES: To determine outcome and changes in health-related quality of life (QOL) in medical intensive care patients. DESIGN AND SETTING: Prospective comparison of QOL before and 6 months after intensive care unit (ICU) admission in a 12-bed noncoronary medical ICU of a university hospital. PATIENTS: All 325 consecutively admitted adult patients who spent at least 24 h on the ICU were eligible. MEASUREMENTS AND RESULTS: QOL measurements were collected before and 6 months after ICU admission. Comorbidity classified by the Charlson index was 2.44 +/- 1.96. Mean stay in the ICU was 10.4 +/- 15.1 days, mean Acute Physiology and Chronic Health Evaluation II score was 23 +/- 10. Cumulative mortality was: ICU 24 %, hospital 34 %, 6 months 43 %. Relative to baseline, follow-up interviews of 185 survivors revealed no significant changes in the overall QOL score (p = 0.93). The subscales basic physiological activities (p = 0.07) and normal daily activities (p = 0.15) showed a nonsignificant deterioration. A significant improvement was noted for the domain emotional state (p = 0.013). CONCLUSIONS: Six months after admission to a medical ICU most survivors had regained their preadmission health-related QOL. Multivariate analysis showed that preadmission QOL, age, and severity of illness were most strongly associated with follow-up QOL. Of the survivors 86 % were living at home, and all but one of those previously in employment had returned to their former work. Most patients (94%) would undergo ICU treatment again if necessary.

Adolescent↗

PubMed2001

Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer.

Helicobacter pylori (HP) infection is usually accompanied by an increased plasma level of gastrin, a potent mitogen able to induce cyclooxygenase (COX)-2. This study examined (a) the seroprevalence of HP, its cytotoxic protein, CagA, and cytokines (tumor necrosis factor alpha, interleukins 1beta and 8) in 80 patients with colorectal cancers, before and after the removal of tumor, compared with 160 age- and gender-matched controls; (b) the gene expression of gastrin and its receptors (CCKB-R) in the cancer tissue, (c) the plasma levels and tumor tissue contents of gastrin, and (d) the mRNA expression of COX-1, COX-2, and apoptotic proteins (Bax and Bcl2) in cancer tissue and intact colonic mucosa. Anti-HP IgG, anti-CagA IgG seroprevalence, and cytokine levels were analyzed by enzyme-linked immunosorbent assay tests; gene expressions of gastrin, CCKB-R, COX-1, COX-2, Bax, and Bcl2 by reverse transcriptase polymerase chain reaction; and gastrin by radioimmunoassay. The seroprevalence of HP, especially that expressing CagA, was significantly higher in cancer patients than in controls and did not change 1 week after tumor resection while plasma cytokines were significantly reduced after this operation. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and the resection margin; similarly, COX-2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa, where only COX-1 was detected. The colorectal cancer tissue contained several folds more immunoreactive gastrin than cancer resection margin and many folds more than the intact colonic mucosa. We conclude that colon adenocarcinoma and its resection margin overexpress gastrin, its receptors, CCKB-R, and COX-2, and that HP infection may contribute to colonic cancerogenesis via overexpression of gastrin and COX-2, which may account for the stimulation of the tumor growth and the reduction in apoptosis as documented by enhanced mRNA expression of anti-apoptotic Bcl2 over proapoptotic Bax proteins.

Adenocarcinoma↗

PubMed2001

Dynamic contrast-enhanced power Doppler sonography improves the differential diagnosis of liver lesions.

The aim of this paper was to investigate the diagnostic value of dynamic contrast-enhanced power Doppler sonography in the differential diagnosis of liver lesions. We prospectively examined 85 focal liver lesions in 71 patients by real-time gray-scale sonography, power Doppler sonography, and contrast-enhanced power Doppler using two ultrasound contrast agents (Levovist, Optison). Amount and architecture of lesion vascularity and the kinetics of contrast enhancement within the lesions were analyzed. Vascularity was detected in 61% of liver lesions (52/85) by conventional power Doppler, compared to 86% (73/85) by contrast-enhanced power Doppler sonography. Dynamic contrast-enhanced power Doppler identified arterial radial hypervascularity <16 s after contrast injection in 19/22 focal nodular hyperplasias (86%). Irregular hypervascularity was seen with contrast enhancement in the arterial phase in 14/15 hepatocellular carcinomas (93%). In 14/25 hemangiomas (56%), a circular vascularization pattern was noted. Specific lesion diagnosis based on B-scan and conventional and dynamic contrast-enhanced power Doppler sonography led to correct diagnosis in 86% (73/85, 95% confidence interval 78%-94%) compared to 57% (48/85, 95% confidence interval 47%-94%) by B-scan criteria and conventional power Doppler sonography. Contrast-enhanced power Doppler sonography improves diagnostic accuracy in the differential diagnosis of focal liver lesions.

Albumins↗

PubMed2001

Proliferating bile duct epithelial cells are a major source of connective tissue growth factor in rat biliary fibrosis.

Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta1 (TGF-beta1) and thus a potential target for antifibrotic treatment strategies. CTGF is up-regulated in disorders such as atherosclerosis, scleroderma, and fibrosis of kidneys and lungs. We investigated the temporospatial expression patterns of CTGF and TGF-beta1 mRNA in rat livers with acute fibrogenesis (after a single dose of CCl(4)) and with advanced fibrosis (6 weeks after complete bile duct occlusion). Multiprobe ribonuclease protection assay revealed increasing TGF-beta1 and CTGF mRNA levels 6 hours after injection of CCl(4), with peak levels after 72 hours. In biliary fibrosis TGF-beta1 and CTGF mRNA levels increased fourfold and sevenfold, respectively (P: < 0.001). In situ hybridization combined with cell-specific markers revealed CTGF transcripts in desmin-positive cells after a single dose of carbon tetrachloride, whereas no transcripts were found in normal livers. In biliary fibrosis, however, proliferating bile duct epithelial cells were the predominant source of CTGF mRNA. We conclude that in rat liver fibrogenesis CTGF is up-regulated in close association with TGF-beta1 and that, contrary to a previous report, not solely hepatic stellate cells but activated bile duct epithelial cells are the main source of this profibrogenic factor.

Acute Disease↗

PubMed2001

Sensitivity of a simplified forced oscillation technique for detection of upper airway obstruction.

The sensitivity of a simplified variant of forced oscillation technique (FOT) was studied for assessment of dynamic upper airway obstruction during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA). The airway impedance P[FOT] was measured by FOT and the oesophageal pressure (P(oes)) was recorded during stable stage II sleep in 11 patients with OSA. The CPAP level was initially set high enough to completely abolish upper airway obstruction. To induce gradually increasing upper airway re-obstruction, the CPAP pressure was then lowered stepwise. Thirty six such manoeuvres were analysed, blind, to define the first inspiration at which upper airway re-obstruction was detectable by analysis of P[FOT](t(FOT)) and by P(oes)(t(oes)), respectively. On seven occasions t(FOT) and t(oes) occurred together, in the remaining 29 cases t(FOT) preceded t(oes) with a mean latency of 6.0+/-7.7 (0-32) breath cycles. In no case did t(oes) preceed t(FOT). FOT is a highly sensitive tool for the assessment of incipient upper airway obstruction during nCPAP therapy.

Aged↗

PubMed2001

Implication of gastrin in cyclooxygenase-2 expression in Helicobacter pylori infected gastric ulceration.

Gastroduodenal ulcerations have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in pathogenesis of this disease. The HP infection is usually accompanied by hypergastrinemia and enhanced generation of prostaglandins (PG), both implicated in the pathogenesis of peptic ulcerations but no study has been undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the PG production. Since HP infection, usually accompanying peptic ulcerations, results in increased release of gastrin, a potent gastric mitogen that might be capable to induce COX-2 and to generate PG, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric ulcer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) at the margin of gastric ulcer and in the mucosa of antrum and corpus before and after successful eradication of HP, 3) to assess the plasma levels and gastric luminal contents of gastrin before and after HP eradication and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 as well as the PGE2 generation in ulcer margin tissue and gastric antral and fundic mucosa before and after the HP eradication. The trial material included 20 patients with gastric ulcer and 40 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 were examined using RT-PCR with beta-actin as a reference and employing Western blotting for COX-2 expression, while gastrin and PGE2 were measured by RIA. All gastric ulcers were located at smaller curvature within the antral mucosal area. The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric ulcers (85%) than in controls (62.5%). Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in ulcer margin and gastrin mRNA was overexpressed in remaining antral mucosa, while CCK(B)-R mRNA was overexpressed in fundic mucosa of HP infected patients. Similarly, COX-2 mRNA and protein were found in margin of gastric ulcer and in the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated patients in whom ulcers completely healed and gastrin was expressed only in antrum, CCK(B)-R only in corpus, while COX-1 was detected both in antrum and corpus. HP positive gastric ulcer patients showed about three times higher levels of plasma immunoreactive gastrin and about 50% higher luminal gastrin contents than the HP negative controls and this increased plasma and luminal gastrin was normalized following the HP eradication. A significant fall in gastrin and CCK(B)-R mRNA expression was noticed six weeks after HP eradication in gastric antral and fundic mucosa, while COX-2 mRNA completely disappeared after this treatment. We conclude that 1) HP infected gastric ulcer margin coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may be implicated in gastric ulceration via increased release of gastrin that could be responsible for the overexpression of COX-2 that in turn could help ulcer healing through the stimulation of mucosal cell growth, restoration of the glandular structure and angiogenesis in the ulcer area and 3) gastrin produced in HP infected antral mucosa seems to be involved in the induction of COX-2 and PG production by this enzyme and this may contribute to the ulcer healing.

Adult↗

PubMed2001

Modulation of collagen XVIII/endostatin expression in lobular and biliary rat liver fibrogenesis.

BACKGROUND/AIMS: The liver is the major source of collagen XVIII (C18), the precursor of the angiogenesis inhibitor endostatin. In human liver C18 is mainly expressed by hepatocytes. However, its quantitative and temporospatial expression patterns during liver fibrogenesis are unknown. METHODS: We used RNA quantification and in situ hybridization combined with cell-specific markers to study C18 compared to procollagen alpha1(I) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA expression in acute (single dose of CCl4) and chronic (biliary) rat liver fibrogenesis. RESULTS: C18 transcripts were only found in hepatocytes and bile duct epithelia of normal and fibrotic livers, and occasionally in arterial myocytes and hepatic stellate cells. 72 h after CCl4 injection, C18 mRNA levels remained unchanged, while procollagen alpha1(I) mRNA was increased at 72 h and TIMP-1 mRNA peaked at 12 h (P < 0.05). In biliary fibrosis C18 mRNA levels increased 1.8-fold, contrasting with 20- and 4-fold elevated procollagen alpha1(I) and TIMP-1 transcript levels, respectively. CONCLUSIONS: Hepatocytes and bile duct epithelia are the predominant sources of C18 in normal and fibrotic rat liver. Contrary to procollagen alpha1(I) and TIMP-1, C18 expression remains constant in acute fibrogenesis and is upregulated in biliary fibrosis. Modulation of epithelial C18 expression and its processing to endostatin could allow a liver-specific anticancer therapy.

Animals↗

PubMed2001

Prevalence of Helicobacter pylori infection in coronary artery disease and effect of its eradication on coronary lumen reduction after percutaneous coronary angioplasty.

BACKGROUND: Gastric infection caused by Helicobacter pylori has recently been associated with increased risk of coronary artery disease. AIM: To: 1) determine seroprevalence of Helicobacter pylori and its cytotoxin associated gene A in patients with/without coronary artery disease (group A), 2) assess influence of Helicobacter pylori eradication on coronary artery lumen reduction after percutaneous coronary angioplasty (group B) and 3) determine influence of Helicobacter pylori eradication on plasma cytokines, lipids and coagulation factors in patients subjected to percutaneous coronary angioplasty (group B). PATIENTS AND METHODS: Group A included 100 patients with coronary artery disease (subgroup 1) and 100 patients without (subgroup II). For Helicobacter pylori seroprevalence, plasma anti-Helicobacter pylori and anti-cytotoxin associated gene A IgG were examined. Group B included 40 patients with significant single-vessel coronary arterial disease and Helicobacter pylori infection confirmed by 13C-urea breath test and serologically using anti-Helicobacter pylori and anti-cytotoxin associated gene A IgG. Six months after percutaneous coronary angioplasty and triple anti-Helicobacter pylori therapy, the Helicobacter pylori status reassessed by urea breath test was negative in all but two patients of subgroup I subjected to Helicobacter pylori therapy. Coronary angiography and laboratory tests were repeated in both subgroups of group B included in the trial and reduction in coronary artery lumen in these subgroups was compared to baseline after percutaneous coronary angioplasty considered as 100%. RESULTS: Helicobacter pylori seropositivity reached 81.5% of coronary artery disease (subgroup I) and was significantly higher than that in controls without coronary artery disease (subgroup II) (51%), the odds ratio being 4.3 for Helicobacter pylori in coronary artery disease. Cytotoxin associated gene A IgG detection was also significantly higher (47.3%) in coronary artery disease than in controls (28%) giving the odds ratio about 2.3. Mean coronary artery lumen reduction in patients undergoing percutaneous coronary angioplasty + Helicobacter pylori eradication therapy (subgroup I) was significantly (p<0.05) smaller compared to percutaneous coronary angioplasty + placebo-treated subgroup II (22% vs 41%). CONCLUSIONS: 1) There is a significant link between coronary artery disease and infection with Helicobacter pylori, especially expressing CagA proteins, 2) Helicobacter pylori eradication significantly attenuates reduction in coronary artery lumen in coronary artery disease patients after percutaneous coronary angioplasty possibly by elimination of chronic inflammation and decline in proinflammatory cytokine release, and 3) Infection of Chlamydia pneumoniae in these percutaneous coronary angioplasty patients is not affected by eradication therapy.

Adult↗

PubMed2001

CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).

BACKGROUND: There have been contradictory reports on the benefit of CEA and CA 19-9 measurements in patients with metastatic colorectal cancer using palliative chemotherapy. The object of this study was to examine the diagnostic accuracy of monitoring of palliative chemotherapy by means of CEA and CA 19-9. PATIENTS AND METHODS: The tumour markers CEA and CA 19-9 were subjected to serial measurement in patients with metastatic colorectal cancer (n = 90) using palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were compared with objective response according to WHO criteria. 85 patients could be evaluated. 43 patients (51%) initially had elevated CEA (> or = 10 ng/ml) and 33 patients (39%) elevated CA19-9 (> or = 50 IE/ml). In 24 patients (28%), both markers were initially increased. With CEA positive patients, 143 cycles of chemotherapy were carried out, which showed the following response in the various cycles: 21 episodes with progressions (ePD), 69 episodes with no change (eNC), 53 episodes with partial/complete remission (ePR/eCR). With CA 19-9 positive patients, 100 cycles of chemotherapy were carried out with the following results: 21 episodes with progressions (ePD), 48 episodes with eNC, and 31 episodes with ePR/eCR. RESULTS: A CEA rise by at least 50% differentiated between ePD versus eNC/ePR/eCR with a sensitivity of 76% and specificity of 90%. With CEA decreases of at least 30% in 99% of these patient episodes (78 of 79), a tumour progression could be excluded. Patients with an initial drop in CEA after the first cycle of chemotherapy of at least 50% of the initial level had a significantly higher probability of achieving an ePR/eCR in further therapy (relative risk 2.9; P = 0.002). With an CA 19-9 increase of at least 30%, a sensitivity progression of 62% and a specifity of 90% could be calculated. A CA 19-9 decrease of at least 60% excludes a progression in 95% of the patient episodes. CONCLUSIONS: A CEA or CA 19-9 rise is only conditionally appropriate for recording progressions. A progression however, can be excluded with falling levels with high diagnostic accuracy, in which CEA offers a greater degree of certainty than CA 19-9. With a drop in CEA 79 of 143 (= 55%) of the CT scans could be saved, in which case 78 of 79 patient episodes (99%) were correctly assessed as 'no progression'. In patients with an increased CEA and CA 19-9 the CEA determination is sufficient for the further monitoring. A confirmation of these results by multicenter trials can result in a considerable decrease of monitoring costs for palliative treatment.

Adult↗

PubMed2001

Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.

BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Aged↗

PubMed2001

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C.

BACKGROUND/AIM: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. METHODS: Three hundred and sixty-seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. CONCLUSIONS: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.

Adult↗

PubMed2001

Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity.

BACKGROUND/AIMS: Quantitative testing of liver function (QTLF) may allow a prognostic assessment of patients with various liver diseases. However, there are insufficient data about patients with liver cirrhosis due to hepatitis C. PATIENTS/METHODS: 86 consecutive patients (58 males, 28 females, age: 48.3 +/- 11.7 years) with chronic hepatitis C (HCV RNA pos.) underwent sonographically guided liver biopsy to confirm the diagnosis of cirrhosis. QTLF included aminopyrine breath test (microsomal liver function), galactose elimination capacity (cytosolic liver function), sorbitol clearance (liver plasma flow) and indocyanine green clearance (liver perfusion). Values were correlated with the Child-Pugh classification. RESULTS: 55% of the patients (n=47) had cirrhosis of Child-Pugh grade A, 28% of grade B (n=24) and 17% of grade C (n=15). QTLF showed a steady decrease from Child-Pugh grade A to grade B and to grade C. Contrary to markedly reduced tests of metabolic liver function in Child-Pugh grade patients, surrogate tests of hepatic perfusion were at the lower normal limit. All QTLF were significantly reduced in Child-Pugh grade B and C patients compared to healthy controls. Differences between the three Child grades were significant. CONCLUSION: In patients with cirrhosis due to hepatitis C, QTLF correlated inversely with Child-Pugh grades. Since in cirrhosis of grade A, surrogate tests of hepatic perfusion remained at the lower normal limit, whereas those of metabolic function were decreased, QTLF may be a tool to predict prognosis or complications in early cirrhosis due to chronic hepatitis C.

Aminopyrine↗

PubMed2001

Adverse drug reactions in patients with gastroenterological diseases: does age increase the risk?

BACKGROUND: It has been claimed that the risk of adverse drug reactions increases with age. However, only limited data exist for disease-group specific risks and none for patients with liver and gastrointestinal diseases. AIMS: To determine the incidence and characteristics of adverse drug reactions and the physicians' awareness of adverse drug reactions. METHODS: During a 7-month period, a prospective survey of 532 male patients (158 aged 65 years or older; 30%) was conducted on a hepatogastroenterological ward of a tertiary-care university hospital, using intensive bedside and computer-assisted drug surveillance methods. RESULTS: No difference was found in the overall rate of adverse drug reactions between older and younger patients (25.9% vs. 24.2%) during 6213 treatment days. However, a significantly higher risk for developing adverse drug reactions could be shown for the elderly with biliary tract diseases (P < 0.01). Independently of age, patients suffering from gastric ulcers, acute episodes of pancreatitis, cholangitis or inflammatory bowel diseases were at high risk of adverse drug reactions. Adverse drug reaction-associated mortality was encountered in four elderly and none of the younger patients. Secondary pharmacological effects and drug toxicity were the main types of adverse drug reactions for both age groups. Although 75.3% of the adverse drug reactions were predictable, only 37.5% of all adverse drug reactions were recognized by the staff physicians. CONCLUSION: In hepatogastroenterological patients, advancing age was not associated with an overall increased risk of adverse drug reactions except for patients with biliary tract diseases. In the elderly, adverse drug reactions were more severe and carried higher mortality. Guidelines and educational programs should be developed to increase the awareness of adverse drug reactions and their prevention, especially in high risk patients and, thus, to improve patient outcomes.

Age Factors↗

PubMed2001

Expression of hepatocyte growth factor, transforming growth factor alpha, apoptosis related proteins Bax and Bcl-2, and gastrin in human gastric cancer.

BACKGROUND: Gastric cancer is one of the most frequent neoplasms and a leading cause of the death world-wide. In recent years, epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H. pylori. The exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remains unclear. There is evidence that the up-regulation of certain growth factors could play an important role in the promotion of the gastric carcinogenesis. AIMS: The present study was designed to determine the gene expression of major known growth factors such as transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and gastrin in the gastric cancer tissue, the surrounding mucosa and, for comparison, in the normal gastric mucosa. Furthermore, the luminal and plasma levels of gastrin in patients with gastric cancer were determined. In addition, the gene and protein expressions of apoptosis-related proteins such as Bax and Bcl-2 were investigated by reverse transcription-polymerase chain reaction and Western blot. Twenty-five gastric cancer patients and 40 age- and gender-matched control subjects hospitalized with non-ulcer dyspepsia were included into this study. RESULTS: An overall H. pylori-seropositivity among gastric cancer patients was about 72% and was significantly higher than in the controls (56%). The prevalence of CagA-positive strains was also significantly higher among gastric cancer patients than in controls (56% vs. 32%). The gene expression of HGF and TGFalpha was detected more frequently in gastric cancer tissue samples than in normal gastric mucosa (52% vs. 12% for HGF and 48% vs. 24% for TGFalpha). The extent of protein expression in Western blotting analysis for HGF and TGFalpha correlated with the mRNA expression of these factors. Gene expression of gastrin was detected in the antrum of all tested patients and in the majority (84%) of gastric cancer patients. The median plasma and luminal concentrations of gastrin in gastric cancer patients were significantly higher than in controls. The gene expression of bcl-2 was detected in all (100%) and that of proapoptotic bax only in 56% of gastric cancer samples. In comparison to the surrounding non-tumorous tisssue, the gene expression of bax was significantly down-regulated and the gene expression of bcl-2 was up-regulated in gastric cancer tissue. At the protein level, Bax was not detectable and Bcl-2 was seen in 80% of gastric cancer samples. CONCLUSIONS: It is concluded that the patients infected with H. pylori, especially with CagA-positive strains, are at a higher risk of developing a gastric cancer. An increased production and release of gastrin, as well as an over-expression of growth factors such as HGF and TGFalpha, might contribute to the gastric carcinogenesis. In addition, a dysregulation of the Bax/Bcl-2 system with significant up-regulation of Bcl-2 is observed in gastric cancer.

Adult↗

PubMed2001

Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease.

BACKGROUND & AIMS: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). METHODS: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI <150) at week 14. RESULTS: Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups. CONCLUSIONS: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

Adult↗

PubMed2001

Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems.

The short-term prognosis of acutely ill patients with cirrhosis is influenced by the degree of hepatic insufficiency and by dysfunction of extrahepatic organ systems. The purpose of this study was to assess and compare the prognostic accuracy of the Child-Pugh classification, the Acute Physiology and Chronic Health Evaluation (APACHE) II system and the Sequential Organ Failure Assessment (SOFA) for predicting hospital mortality in patients with cirrhosis when used 24 hours after admission to a medical intensive care unit (ICU). Prospective data were recorded on 143 patients. Cumulative mortality rates were 36% in the ICU, 46% in the hospital, and 56% at 6-month follow-up. By using the area under receiver operating characteristic (AUROC) curves, the SOFA showed an excellent discriminative power (AUROC 0.94), which was clearly superior to the APACHE II (AUROC 0.79) and the Child-Pugh system (AUROC 0.74). Hospital mortality rates below and above a cutoff of 8 SOFA points were 4% and 88%, respectively (P <.0005). The SOFA score also reflected resource use during the ICU treatment as measured by daily workload and length of stay. The SOFA is an easily applied tool with excellent prognostic abilities and can be used to enhance clinical judgment of prognosis as well as providing patients and families with objective information.

Adult↗

PubMed2001

Weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) with folinic acid (FA) in adjuvant therapy of colon cancer.

After curative resection (R-0) of primary colon cancer or curative metastases resection, the efficacy, toxicity and compliance of a weekly 24-h infusion of high-dose 5-FU with folinic acid was examined in a prospective feasibility trial. From June 1995 to June 1997, 19 patients were included, 11 patients with UICC stage III and 8 patients with UICC stage IV colon cancer. The patients received weekly 500 mg/m2 of calcium folinic acid (Rescuvolin) as a 1-2 h-infusion on an outpatient basis following a 24-h infusion of 2,000 mg/m2 5-FU via a pump system (intermate LV5 Baxter). The adjuvant therapy was administered for 6 months. 90% of the patients received the planned 18 chemotherapy applications. The total 5-FU dose given to each patient amounted to 34.4 g/m2 in 6 months, thus corresponding to 95% of the planned 5-FU total dose. The main toxicity was diarrhea CTC toxicity grade 3 in the case of 16% of the patients. After a median follow-up of 51 months (range: 37-59 months), 82% of the patients (9 out of 11) with stage III remained free of recurrence. The 2 cases of recurrence belonged to the pN2 subgroup. In stage IV only 12% of the patients (1 out of 8) remained free of recurrence. On an adjuvant basis, a weekly 24-h infusion of high-dose 5-FU with folinic acid is accompanied by a good complicance and a high-dose intensity of 5-FU. Now it is tested within randomized phase III trials of the "Arbeitsgemeinschaft Gastroenterologische Onkologie (AGO)" of the "Deutsche Gesellschaft für Verdauungs- und Stoffwechselerkrankungen" for UICC stage III colon cancer. Concerning stage IV, adjuvant therapy was not effective, a fact that seems to justify new drugs and new therapeutic strategies.

Adult↗

PubMed2001

[Liver toxicity of drugs of plant origin].

Herbal drugs are widely used and often contain highly active pharmacological compounds. Recently, reports have mounted about hepatotoxicity of herbal remedies which ranges from mild liver enzyme alterations to chronic liver disease and liver failure. Hepatotoxicity of Chinese herbs has been recognized, e.g. during treatment of patients with atopic eczema. However, the toxic compounds remain to be determined. Hepatic veno-occlusive disease may result from pyrrolizidine alkaloids which are contained in numerous plants worldwide. Teucrium chamaedrys, commonly referred to as germander, may cause hepatitis and even liver cirrhosis. Significant hepatotoxicity has also been observed after the ingestion of chaparral. Recently, greater celandine, which is widely used for biliary disorders and dyspepsia, was identified as a cause of cholestatic hepatitis. Hepatotoxic reactions have also been observed after the ingestion of Atractylis gummifera, Callilepsis laureola, Senna, Kavapyrone and Pulegium. The aim of this review is to summarize potentially hepatotoxic herbal remedies, to further elucidate their mechanisms of toxicity and thereby underline the likelihood of plants to be the cause of liver damage.

Chemical and Drug Induced Liver Injury↗