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Biomedical subjects

R Guimbaud

Publications and source records attributed to R Guimbaud.

27 records · Page 2Linked to original sources
PubMed1998

Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course.

The pleiotropic cytokine leukemia inhibitory factor (LIF) possesses proinflammatory properties in common with tumor necrosis factor (TNF-alpha), interleukine (IL) -1 and -6, such as the induction of acute phase protein synthesis. LIF may have chemotactic activity through the induction of IL-8 production. LIF is produced by normal and tumoral cells and appears to facilitate in vivo rat colon carcinoma cells growth. Inflammatory bowel diseases, ulcerative colitis (UC) in particular, are histologically characterized by the infiltration of the colonic mucosa with activated neutrophils, macrophages and lymphocytes. Cytokines with their inflammatory as well as their regulatory activities may play a role in the perpetuation and possibly the initiation of inflammation in this disease and its local and/or systemic complications. Moreover, colorectal cancer is a late well identified complication in patients with long standing inflammatory bowel disease, UC in particular. Taken together, these results suggest that LIF could be involved in tumorigenic and/or metastatic processes of colorectal cells in UC patients. The aims of the present study was to quantify and to compare the colonic and systemic productions of LIF in UC patients. We showed for the first time in patients with UC, a high local production of LIF well correlated with IL-8 production. We also analyzed the effect of LIF on a human colon carcinoma cell line HT29. We demonstrated that LIF stimulated HT29 cell growth in a dose dependent-manner. These results suggest that LIF may play a critical role in the susceptibility of colonic host cells to tumor growth in patients with UC.

Adult↗
PubMed1997

How to predict carboplatin clearance from standard morphological and biological characteristics in obese patients.

BACKGROUND: We previously proposed a formula to predict carboplatin clearance (CL) from four patient characteristics: plasma creatinine level, body weight, age, and sex (J Natl Cancer Inst 1995; 87: 573). Its accuracy was studied in a subpopulation of obese patients. PATIENTS AND METHODS: Twenty-five patients (16 male and 9 female, 23 to 82 years old) were studied. They were 20% to 67% (median 36%) over the ideal weight which was calculated according to the Lorentz equation. Their actual CL was obtained individually by the Siphar program. The pharmacokinetic population program NONMEM was used to determine the best value of substitution for weight in the formula. RESULTS: By using the actual weight, CL was significantly over predicted (by more than 20% for 7 of 25 patients). By using the mean value between the ideal and the actual weight, a good prediction of CL was obtained: the percentage of error ranged from -21% to +22%. CONCLUSION: The formula is applicable to obese patients if both ideal and actual weights are taken into account.

Adult↗
PubMed1997

Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans.

Exocrine pancreas from different species behaves differently in response to the presence of intact or digested nutrients in the duodenum. A failure of cholecystokinin (CCK) release after a meal has been shown among patients with exocrine pancreatic insufficiency. This abnormality could be restored by the administration of pancreatic extracts, suggesting that digested rather than intact nutrients are responsible for the release of CCK and subsequently gallbladder contraction in humans. The aim of this study was to determine the specific role of different lipidic stimuli in humans. Seven male patients (mean age, 52 years) with pancreatic insufficiency secondary to chronic pancreatitis were selected. Pancreatic insufficiency was considered severe in five of them (lipase output, < 1,000 IU/min) and moderate in another two (lipase output, > 1,000 and < 2,300 IU/min). Plasma CCK (by bioassay), gallbladder contraction (by ultrasound), and enzyme output (chymotrypsin) in response to duodenal administration of either oleic acid as free fatty acids or 20% Intralipid as triglycerides were measured in each patient with at least a 48-h interval between each test. In all these patients with pancreatic insufficiency, duodenal perfusion of free fatty acids generated a more pronounced (91 +/- 11 vs. 49 +/- 21 pM) and faster (15 vs. 30 min) (p < 0.05) CCK release than triglycerides. Furthermore, gallbladder contraction was more efficient when free fatty acids instead of triglycerides were administered in the duodenum (86 +/- 5 vs. 69 +/- 4%) at 10 min (p < 0.05) and (73 +/- 8 vs. 51 +/- 5%) at 15 min (p < 0.03). Among patients with measurable residual pancreatic function, enzyme outputs were shown to be higher during free fatty acid than triglyceride perfusion. In humans, free fatty acids rather than triglycerides, when present in the duodenum, stimulate CCK release and gallbladder contraction. In patients with moderate pancreatic insufficiency this phenomenon may increase residual enzymatic secretion. These results allow us to encourage the development of enzymatic preparations as acid-resistant lipases that cause a fast release of free fatty acids in the duodenum.

Adult↗
PubMed1995

Intraluminal excretion of PAF, lysoPAF, and acetylhydrolase in patients with ulcerative colitis.

PAF-acether (PAF) is a phospholipid synthesized by numerous inflammatory cells. PAF can produce several pathological changes in various organs, especially in the colon. In animals PAF causes colonic ulceration and inflammation, which are similar to the anatomic lesions seen in human ulcerative colitis. The aim of this study was to measure in vivo colonic production of PAF in active ulcerative colitis using a modified colonic perfusion method. Ten patients with active ulcerative colitis and six control patients were investigated. A colonic segment was continuously perfused with a buffer and the liquid was recovered 20 cm distally, after a 45-min period of equilibration, at 20-min intervals. PAF, lysoPAF, and acetylhydrolase were measured in the colonic samples. PAF and lysoPAF outputs were significantly higher in patients with active ulcerative colitis compared to controls patients. There was a significant correlation between colonic PAF output and, respectively, macroscopic mucosal lesions and myeloperoxidase colonic output. We thus conclude: (1) the colonic perfusion method allows in vivo study of the metabolism of PAF during ulcerative colitis and could also be used to study the efficiency of PAF antagonists in UC; and (2) colonic production of PAF is increased during ulcerative colitis and correlated to local injury and inflammation. Whether or not PAF plays a role in the pathogenesis of ulcerative colitis remains open for further investigations.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1992

Microscopic examination of bile directly collected during endoscopic cannulation of the papilla. Utility in patients with suspected microlithiasis.

The usefulness of microscopic examination of pure bile directly collected from the biliary tract during endoscopic retrograde cholangiography and without hormonal simulation was prospectively evaluated in 72 patients. According to clinical, biochemical, ultrasonographic, and radiographic data, the patients were separated into two groups: group 1, patients with proven stones (N = 50), and group 2, patients with suspected microlithiasis presenting symptoms suggestive of cholelithiasis but without evidence of macroscopic stones at echography or cholangiography (N = 22). Cholesterol crystals and/or bilirubinate granules were observed (eg, positive examination) in the bile of 41 of the 50 patients of group 1 (82%). Among patients of group 2, seven (32%) had a positive bile examination: cholecystectomy (N = 2) or endoscopic sphincterotomy (N = 5) disclosed minute stones in all cases. In the 15 patients of group 2 with a negative bile examination, cholecystectomy (N = 3), sphincterotomy (N = 2), and clinical (and/or echographic) 20-month follow-up (N = 9) revealed biliary lithiasis in only one patient, in whom recurrent cholangitis led to disclosure of one bile duct stone. According to these results, microscopic examination of bile samples collected during endoscopic retrograde cholangiography exhibited a sensitivity and a specificity for cholelithiasis recognition of 82.7% and 100%, respectively, with a positive predictive value of 88%. We conclude that the accuracy of this method makes it useful to investigate and manage patients with suspected microlithiasis.

Aged↗
PubMed1990

Decreased high affinity state in platelet alpha 2-adrenoceptors from diabetic patients with orthostatic hypotension.

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]yohimbine binding) were investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension due to autonomic neuropathy as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One-minute standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and KD) calculated by [3H]yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state (inhibition experiments of [3H]yohimbine by UK14,304, a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). Since platelet alpha 2-adrenoceptors are thought to be a suitable index of vascular alpha-adrenoceptors, the decrease in platelet alpha 2-adrenoceptors in high affinity state could explain the occurrence of orthostatic hypotension in insulin-dependent diabetic patients. Multiple pathophysiological mechanisms underly orthostatic hypotension in insulin-dependent diabetic patients and include anomalies both in the sympathetic nervous system and in alpha 2-adrenoceptor coupling.

Adrenergic alpha-Agonists↗