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Biomedical subjects

J Gelin

Publications and source records attributed to J Gelin.

At least 19 recordsLinked to original sources
PubMed2005

Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.

OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.

Aged↗
PubMed2004

Predictors of treatment outcome in intermittent claudication.

OBJECTIVE: To derive formulae to predict the likely 12-month health-related quality of life outcome following different treatments for intermittent claudication (IC). DESIGN: A prospective, randomized, controlled study. MATERIALS: One hundred and seventy-one unselected patients with stable IC were sequentially randomized to invasive therapy, supervised physical training or observation. Hierarchical analysis was used to identify significant predictors of outcome. RESULTS: The strongest outcome predictors were baseline values of the respective outcome variables in all groups. No more than two significant secondary predictors were identified for each outcome variable and no outcome variable was a predictor of any other outcome variable. Resulting prediction equations achieved between 61 and 90% concordance with improvement (75% considered adequate), with best prediction for invasive therapy and poorest for observation. Suggested cutpoints for the various endpoints in the three groups had sensitivities ranging between 65 and 100% and false positive rates between 5 and 50%. CONCLUSIONS: The derived equations adequately predicted improvement on the various outcome variables in invasive therapy and supervised physical training, and may serve as aids in selecting patients likely to benefit most from a particular treatment strategy. The uniqueness of the outcome variables underscores the importance of implementing a comprehensive set of endpoints relevant to the impacts of the condition.

Aged↗
PubMed2004

Multicenter clinical experience with large core soft tissue biopsy without vacuum assistance.

The increasing interest in accurate pretreatment diagnosis of solid tumours by morphology, immunohistochemistry, genetics and molecular biology requires clinicians to obtain undamaged large core biopsies. Simultaneously, medical imaging and surgery give priority to minimal tissue injury, affordable technology and optimal patient compliance. A new large core soft tissue biopsy device has been developed to meet the above criteria. After intensive preclinical testing, 30 patients gave informed consent and 26 underwent the new diagnostic biopsy procedure. The sample was studied by morphology, immunohistochemistry and, where indicated, by molecular biology. Successful diagnosis was considered when in line with clinical follow-up and, as for all malignant lesions, when confirmed by open biopsy or surgery. No difficulties in the technique were encountered in 25 patients. In one patient the procedure was prematurely stopped because of anxiety. In all other 25 procedures a complete diagnosis was reached with regard to morphology, immunohistochemistry and molecular biology. A number of radiologists suggested some automation of the technique. This new large core soft tissue biopsy system performs well in the clinical context without injury to the breast parenchyma or artefacts in the harvested tissue specimen. The system meets almost all of the proposed technical and financial requirements. Automation is underway.

Artifacts↗
PubMed2001

Treatment efficacy of intermittent claudication by invasive therapy, supervised physical exercise training compared to no treatment in unselected randomised patients II: one-year results of health-related quality of life.

OBJECTIVE: to compare the effectiveness of invasive therapy, supervised physical training and no treatment in terms of health-related quality of life (HRQL) in patients with intermittent claudication (IC). DESIGN: a prospective, randomised, controlled study. MATERIALS: a total of 253 unselected patients with stable IC were sequentially randomised into 3 balanced treatment groups. At 1 year follow-up data from a battery of generic and disease specific HRQL questionnaires, and global indices of quality of life and physical condition were available in 171 patients. RESULTS: compared with a non-diseased reference group, claudicants were substantially limited in daily physical functioning, but little affected regarding emotional, cognitive and social functioning, or well-being. Invasive therapy yielded significantly greater improvements in some aspects of physical functioning and walk-related symptoms than training. Training was not superior to invasive therapy on any HRQL dimension and superior to no treatment on only one dimension. Treatment effects, however, were generally small-to-moderate and levels of physical dysfunction in all groups remained higher than reference values. CONCLUSIONS: invasive therapy is more effective than supervised training in alleviating illness-specific symptoms and improving certain aspects of physical functioning - the primary HRQL domains impacted on by IC and the principal goals of its treatment. However, since treatment effect sizes were at most moderate and given that untreated claudicants reported at most small deterioration in HRQL, the level of evidence supporting invasive therapy is modest.

Activities of Daily Living↗
PubMed2001

Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.

OBJECTIVES: to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. DESIGN: prospective, randomised study. METHODS: a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis. RESULTS: invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure. CONCLUSION: invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.

Adult↗
PubMed2000

Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids.

The potential interaction between cyclooxygenase (Cox) and NO metabolic pathways in the control of local tumor growth was evaluated. Mice bearing either a sarcoma-derived tumor (C57B1; MCG 101) or a malignant melanoma (C3H/HeN; K1735-M2) were used. These models were principally different because they demonstrate, in tumor hosts, conditions with and without cancer cachexia, seemingly related to high and low production of prostanoids, respectively. Cox inhibitors (Cox-1 and Cox-2) decreased tumor growth by 35-40% in MCG 101-bearing mice but had no such effect on melanoma-bearing mice, despite the expression of the Cox-2 protein in melanoma cells. Indomethacin reduced prostanoid production in both tumor (MCG 101) and host tissues and reduced tumor cell proliferation, mainly in vivo. Nitric oxide synthase (NOS) inhibitors (N(omega)-nitro-L-arginine methyl ester and N(omega)-nitro-L-arginine) reduced tumor growth in vivo by approximately 50% in both tumor models. Tumor growth reduction, related to NOS inhibition, was unrelated to prostanoid production and was an in vivo phenomenon in both tumor models. Specific inhibitors of inducible NOS activity, unexpectedly, had no effect in any tumor model, although inducible NOS protein was present in tumor tissues in large amounts. A combination of Cox and NOS inhibitors had no additive effect on tumor growth (MCG 101). Cox inhibition increased tumor tissue (MCG 101) expression of cNOS mRNA but had no significant effect on tumor tissue expression of the transferrin receptor, vascular endothelial growth factor, or basic fibroblast growth factor. NOS inhibition increased tumor tissue content of cNOS mRNA but showed as well a trend to increase mRNA content of the transferrin receptor and vascular endothelial growth factor. Our results suggest that NOS inhibitors can decrease the local growth of tumors that are either responsive or unresponsive to Cox inhibition. This effect may reflect cross-talk between Cox and NOS pathways within or among tumor cells, or it may represent unrelated effects on tumor and host cells. Whether NO inhibition may be used therapeutically in clinical tumors that are unresponsive to eicosanoid intervention remains to be evaluated.

Animals↗
PubMed1996

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.

Cachexia↗
PubMed1994

Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors.

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 +/- 28 days to 510 +/- 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.

Aged↗
PubMed1994

Imaging of polypoid endoluminal growing bile duct tumors.

We reviewed the radiological documents and protocols of 196 cases of bile duct tumors examined over a period of 12 years: 20 of them (10.2%) presented with a polypoid endoluminal growth. The aim of this study was to provide a better knowledge about the radiological features of this less frequent kind of tumor. In these 20 cases, the correct diagnosis of bile duct lesion was provided in 100% by E.R.C.P., P.T.C., U.S. as well as C.T., and in 42% by arteriography. The correct diagnosis of tumor was made by E.R.C.P. in 86%, by P.T.C. in 88%, by U.S. in 61%, by C.T. in 63%, and by arteriography in 25%. A correct diagnosis of tumor could be reached in all cases by combination of several examination techniques. The anatomopathological diagnosis was: bile duct adenocarcinoma (7 cases), adenocarcinoma of the ampulla of Vater (4), villous adenoma of Vater's ampulla (2), cystadenoma (1), cystadenocarcinoma (1), hepatocellular carcinoma (1), apudoma (1), and metastases (3).

Adenocarcinoma↗
PubMed1993

Acute-phase proteins in response to tumor growth.

This study has evaluated the relationship between tumor growth and induction of acute-phase proteins. It has also determined whether an intact cellular immunity is obligatory for a fully expressed acute-phase plasma protein response in the presence of a highly antigenic tumor. Quantitatively, acute-phase responses (protein synthesis, plasma concentrations, hepatic RNA content, anorexia) were proportional to tumor burden. Anti-inflammatory drugs (indomethacin 1 micrograms/g body wt, dexamethasone 0.5 micrograms/g body wt) had no direct effect on the attenuation of the systemic acute-phase responses, but did affect them indirectly by decreasing tumor growth. Immune suppression (cyclosporine A at 20 or 60 micrograms/g body wt) had no effect on either acute-phase reactions or local tumor growth. In endotoxin-stimulated (lipopolysaccharide) normal mice, immune suppression aggravated anorexia and caused high mortality, while dexamethasone partly reversed these effects in endotoxin-stimulated mice. Plasma levels of acute-phase proteins correlated to circulating levels of IL-6 in untreated tumor-bearing mice, but this relationship was not obvious in either drug-treated tumor-bearing or endotoxin-stimulated mice. Tumor tissue induced the synthesis of different acute-phase proteins compared to endotoxin. However, disintegrated normal liver tissue induced the synthesis of serum amyloid protein to the same extent as the growing tumor. This effect was primarily associated with the mitochondrial/lysosomal and microsomal liver cell fractions. In conclusion, the overall acute-phase protein response is not a modulating factor of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1992

Co-variation between walking ability and circulatory alterations in patients with intermittent claudication.

Unselected patients (n = 183) with subjective symptoms of intermittent claudication were examined clinically and by various circulatory tests (calf blood-flow, ankle, toe pressures). The aims of the present study were to evaluate to what extent the central or peripheral circulation is limiting in unselected patients with subjective symptoms of intermittent claudication, to determine the co-variation between the maximum walking capacity and traditional haemodynamical measures mentioned above and to evaluate to what extent a traditional bicycle ergometer exercise test and treadmill walking test give similar information regarding maximum performance. Eighty-five per cent of all patients were or had been smokers and 16% were diabetics. The mean ankle/brachial blood pressure index was 0.58 +/- 0.02 and the average post-ischemic maximum calf bloodflow was 13.3 +/- 0.6 ml/min/100 ml tissue. Leg arterial insufficiency was the limiting factor of walking capacity in 90% of all patients at 87 +/- 2 W corresponding to a walking distance of 282 +/- 13 m, while leg exhaustion was the limiting factor in 80% of the patients during test on the bicycle ergometer at maximum 84 +/- 2W. The mean maximum walking capacity for all patients was 86 +/- 3W and the mean maximum capacity on the bicycle ergometer was 87 +/- 2W. The ankle/brachial index showed only a weak correlation (r = 0.30, p < 0.002) to walking capacity. Our results demonstrate that the maximum walking capacity on a treadmill agrees with mean values of maximum exercise capacity on a bicycle ergometer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Effects of indomethacin, cytokines, and cyclosporin A on tumor growth and the subsequent development of cancer cachexia.

C57BL/6J mice bearing a low or undifferentiated rapidly growing tumor were treated daily with either i.p. injections of the recombinant cytokines interleukin(IL)-1 alpha, IL-1 beta (21 ng/g), and tumor necrosis factor alpha (21 ng/g) or s.c. injections of cyclosporin A (60 micrograms/g) or indomethacin (1 micrograms/g). In some experiments, indomethacin was administered in the drinking water corresponding to the amount of s.c. injections. Survival and the time course of tumor growth and food and water intake were measured. The nutritional state (body composition) of the animals was registered at spontaneous death in the course of tumor disease. Indomethacin prolonged survival from 14 +/- 1 to 22 +/- 1 days in tumor-bearing mice when administered either in the drinking water or as s.c. injections. This effect, which was due to tumor growth inhibition, was equally effective irrespective of whether indomethacin was instituted on Day 1, 5, 7, or 9 following tumor implantation. Indomethacin did not inhibit tumor cell growth in vitro. Indomethacin-treated tumor-bearing mice were also less anorectic than untreated tumor-bearing mice, and their nutritional state, particularly lean body mass, was significantly improved by indomethacin at doses (1 micrograms/g) that did not influence the food intake or body composition in non-tumor-bearing mice. At spontaneous death, indomethacin-treated tumor-bearing mice had a significantly larger tumor burden when accounting for their degree of malnutrition as compared with untreated tumor bearers. Indomethacin did not decrease the elevation in hepatic concentrations of RNA seen in response to tumor progression. Adherent peritoneal macrophages from tumor-bearing mice had a lower prostaglandin E2 synthesis compared with macrophages from non-tumor-bearing controls in the basal state (1100 +/- 150 pg/10(6) cells versus 3700 +/- 922 pg/10(6) cells). Lipopolysaccharide stimulated macrophages from tumor-bearing mice to produce significantly more prostaglandin E2 in vitro compared with control macrophages (39,500 +/- 4208 pg/10(6) cells versus 12,500 +/- 4330 pg/10(6) cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia.

The aim of this study was to evaluate to what extent tumor necrosis factor alpha (TNF-alpha) and interleukin 1 may explain the development of experimental cancer cachexia. For this purpose, C57BL/6J mice bearing a transplantable low differentiated rapidly growing tumor were passively immunized every other day with rabbit or rat neutralizing immunoglobulins against either TNF-alpha (anti-TNF) or against an interleukin 1 receptor (anti-IL-1r). Anti-IL-1r in itself had no agonistic effect to the type I, T-cell/fibroblast IL-receptor. Tumor-bearing mice receiving either preimmune antiserum or nonimmune rat hybridoma IgG served as controls. Anti-TNF and anti-IL-1r inhibited tumor growth significantly, as measured by a lower wet and dry tumor weight at the end of 11 days of antiserum treatment (P less than 0.05). The acute phase response in tumor-bearing animals, measured as an increase in liver weight, hepatic RNA content, and increases in plasma concentrations of circulating IL-6, serum amyloid P, transferrin, complement (C3), and a decrease in plasma albumin, were unaffected by the specific antiserum treatments. Food intake, which declined significantly in pre/nonimmune injected tumor-bearing controls, was significantly improved in tumor-bearing animals immunized against TNF-alpha or the IL-1r. Whole body lipid content showed a trend to improvement in specifically immunized animals (P less than 0.07). The effects on whole body fat-free dry weight were insignificant, although numerically higher in specifically immunized tumor-bearing animals. The combination of anti-TNF and anti-IL-1r antiserum had no additive effects compared to single antiserum treatment suggesting that the two antibody treatments acted through a common mechanism. Cultured tumor cells, established from growing tumors, were sensitive to anti-TNF and anti-IL-1r, which both reduced tumor growth in vitro. This inhibitory effect by the antiserum could in part be reversed by the addition of recombinant IL-1 alpha and TNF alpha. We conclude that both TNF and IL-1 are involved in tumor growth and thus the progression of cancer cachexia. It seems as if the role of TNF and IL-1 was to promote tumor growth rather than restrict tumor growth in the present model. In this sense both TNF and IL-1 may act as tumor growth factors.

Acute-Phase Proteins↗
PubMed1990

Tumor necrosis factor-alpha and interleukin-1 alpha production in cachectic, tumor-bearing mice.

Weight-stable mice bearing a syngeneic, methylcholanthrene-induced, rapidly growing tumor lost approximately 22% of their lean tissue, became significantly hypoalbuminemic and had a marked increase in serum amyloid P concentrations during progressive tumor growth. Tumors from cachectic mice were producing both TNF-alpha and IL-1 alpha in vivo as documented by the presence of TNF-alpha and IL-1 alpha mRNA and immune-reactive protein for IL-1 alpha. Only spleens from tumor-bearing mice had statistically significantly elevated quantities of IL-1 mRNA. In general, alterations in tissue concentrations of IL-1 mRNA in tumor-bearing animals agreed qualitatively with those found in endotoxin-stimulated, non-tumor-bearing control mice. However, endotoxin-stimulated mice had significantly elevated tissue concentrations of TNF mRNA in spleen and livers, while TNF mRNA levels were not significantly increased in any host tissues. Cytokine mRNA levels in tumor tissue were not higher than those found constitutively in various tissues from non-tumor-bearing control animals. Plasma from tumor-bearing mice and endotoxin-stimulated controls contained high levels of IL-6 but low (endotoxin-stim.) or no measurable levels (tumor-bearing) of either IL-1 or TNF. When tumor cells from cachectic mice were placed into long-term cell culture, immune reactive TNF-alpha and IL-1 alpha were produced, but IL-6 bioactivity ws not produced in measurable amounts.

Animals↗
PubMed1990

The effect of indomethacin on food and water intake, motor activity and survival in tumour-bearing rats.

This investigation has addressed the question whether food and water intake, motor activity and tumour growth are influenced by indomethacin in experimental cancer. Growing rats implanted with a methylcholanthrene-induced sarcoma were studied in metabolic cages connected to a computer. Food intake, water consumption and motor activity were continuously recorded over 30 days following tumour implantation. Treated tumour-bearing animals received indomethacin 1.0 mg/kg per day in drinking water. Food intake declined early in untreated tumour-bearing animals, but water intake was not affected. Motor activity decreased in untreated tumour-bearing animals from days 16-17 onward. Indomethacin treatment prolonged survival and 40% of these tumour-bearers were 'complete responders'. In some animals tumour growth was only marginally affected, but survival was still significantly improved ('partial responders'). Food intake was significantly improved in complete responders. Thus this positive effect seen in complete responders was secondary to less active tumour growth. Motor activity was also significantly higher in responders compared with non-responders.

Animals↗
PubMed1989

The cause of death in non-metastasizing sarcoma-bearing mice. A study with relevance for tumor treatment experiments in mice.

Adult sarcoma-bearing mice were used to demonstrate whether hypoglycemia was the immediate cause of death in experimental animals with rapidly growing tumors without metastases. This kind of tumor model is representative of the majority of animal models used in experimental cancer research. Tumor-bearing animals died with severe hypoglycemia under all experimental conditions, while pair-killed controls were normoglycemic. Anorexia prevented tumor-bearing animals from attenuating the hypoglycemia by drinking glucose-containing water while completely starved control animals survived more than 14 days with glucose-containing water as the only energy source. Adrenalectomy shortened survival in tumor-bearing animals, but survival of adrenalectomized tumor-bearing animals could be normalized by daily injections of pharmacologic doses of hydrocortisone (25 mg/25 g body wt/day) but not by physiologic replacement (20 micrograms/25 g body wt/day). Injections of pharmacologic doses of hydrocortisone did not influence on survival or body composition in tumor-bearing animals with intact adrenals. Glucagon was without effect on either survival, tumor growth or body composition. Based on the results in this study and in our previous reports we conclude that hypoglycemia is the cause of death in the majority of murine tumor models. This hypoglycemic theory is important, since any treatment modality in animal experiments that influences glucose metabolism in the host may indirectly change tumor growth and may thus be misinterpreted as a direct tumor effect.

Adrenalectomy↗