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Biomedical subjects

P Rampal

Publications and source records attributed to P Rampal.

At least 19 recordsLinked to original sources
PubMed2001

Antiproliferative effects of nitrosulindac on human colon adenocarcinoma cell lines.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of colon cancer, but their use is limited by toxicity in the gastrointestinal tract. The coupling of a nitric oxide-releasing moiety to NSAIDs strongly reduces these side effects. We demonstrated that the NO-releasing sulindac (nitrosulindac) has much more potent effects on colon adenocarcinoma cell lines compared to sulindac. Moreover, it could inhibit the growth of cells in soft agar experiments, demonstrating the antineoplastic activity at low concentration of nitrosulindac. However, this reduction in the growth of colon cancer cells seemed to be independent of the classical apoptosis pathway and could be explained by a cytostatic effect. Nitrosulindac caused a light perturbation of the cell cycle parameters not linked to a modification of the levels of p21 or the proliferating cell nuclear antigen. Moreover, neither sulindac, nor nitrosulindac, were able to inhibit the NF-kappa B pathway. These data suggested that nitrosulindac could be a better solution compared to other NSAIDs in the treatment of colon cancer.

Adenocarcinoma↗
PubMed2001

Role of fibrates and HMG-CoA reductase inhibitors in gallstone formation: epidemiological study in an unselected population.

Fibrate derivatives and HMG-CoA reductase inhibitors modify homeostasis of cholesterol. The aim of this study was to assess in an unselected population whether these hypolipidemic drugs are risk factors for cholelithiasis or, conversely, are protective agents. Both sexes, all socioeconomic categories, pregnant women, and cholecystectomized subjects were included. Clinical data collection and gallbladder ultrasonography were both carried out in a double-blind fashion. Fibrate derivatives were predominantly fenofibrate, HMG-CoA reductase inhibitors were simvastatin and pravastatin. On univariate analysis, age (>50 years), sex, and use of fibrates were found to be significantly related to the presence of cholelithiasis. Age, sex, and fibrate treatment remained independently correlated with the presence of gallstones on multivariate analysis. With fibrates, the relative risk for lithiasis was 1.7 (P = 0.04). The HMG-CoA reductase inhibitors were not associated with a protective effect on univariate analysis. Of the lipid-lowering drugs, only fibrate derivatives were found to increase the risk of gallstone formation.

Anticholesteremic Agents↗
PubMed2001

Argon plasma endoscopic section of biliary metallic prostheses.

We report our recent experience of using argon plasma to endoscopically cut biliary Wallstent prostheses in these patients. The first patient had a bleeding duodenal ulceration caused by the impaction of the prosthesis meshes whereas the second patient had an ill-positioned biliary stent with impaction into the opposite duodenal wall. Both prostheses were shortened using argon plasma. In the third patient, the lower extremity of a obstructed biliary Wallstent was positioned in the third duodenum preventing its endoscopic catheterization. After shortening using argon plasma, a new plastic stent could be inserted to allow drainage. The outcomes in these cases demonstrate the feasibility of endoscopically shortening metallic Wallstents after release using argon plasma.

Aged↗
PubMed2001

Implication of mitogen-activated protein kinases in T84 cell responses to enteropathogenic Escherichia coli infection.

Enteropathogenic Escherichia coli (EPEC) infection of T84 cells induces a decrease in transepithelial resistance, the formation of attaching and effacing (A/E) lesions, and cytokine production. The purpose of this study was to investigate the ability of EPEC to activate mitogen-activated protein (MAP) kinases in T84 cells and to correlate these signaling pathways with EPEC-induced cell responses. T84 cells were infected with either the wild-type (WT) EPEC strain E2348/69 or two mutants, intimin deletion strain CVD206 (deltaeaeA) and type III secretion apparatus mutant strain CVD452 (deltaescN::aphA). Infection of T84 cells with WT but not mutant EPEC strains induced tyrosine phosphorylation of several proteins in T84 cells, including the p46 and p52 Shc isoforms. Kinetics studies revealed that ERK1/2, p38, and c-Jun N-terminal kinase (JNK) MAP kinases were activated in cells infected with strain E2348/69 but not with the mutant strains. Inhibition of MAP kinases with PD98059 or SB203580 did not affect the EPEC-induced decrease in transepithelial resistance or actin accumulation beneath the WT bacteria, but these two inhibitors significantly decreased interleukin-8 (IL-8) synthesis. We demonstrate that EPEC induces activation of ERK1/2, p38, and JNK cascades, which all depend on bacterial adhesion and expression of the bacterial type III secretion system. ERK1/2 and p38 MAP kinases were equally implicated in IL-8 expression but did not participate in A/E lesion formation or transepithelial resistance modification, indicating that the signaling pathways involved in these events are distinct.

Adaptor Proteins, Signal Transducing↗
PubMed2001

[Atrophic polychondritis associated with ulcerative colitis].

We report the case of a 46-year-old patient in whom ulcerative colitis had been diagnosed three years ago. He was admitted to the hospital for swelling of the nose. Clinical course and complementary exams led us to diagnose atrophic polychondritis. Twelve cases of such an association have been published so far.

Colitis, Ulcerative↗
PubMed2000

Acarbose and lymphocytic colitis.

We report a case of lymphocytic colitis induced by acarbose. Our immunopathological findings shown before and after rechallenge are consistent with a colonic immune-cell activation by the drug.

Acarbose↗
PubMed2000

Total artificial nutrition is associated with major changes in the fecal flora.

BACKGROUND: Animal studies have demonstrated dramatic changes in the intestinal flora during total enteral (TEN) or parenteral (TPN) nutrition. AIM OF THE STUDY: To assess the impact of TEN and TPN on human intestinal microflora. METHODS: Eight patients on fiber-free TEN, five patients on TPN, and ten controls were studied. Fecal bacteria were identified and numbered (logCFU/g feces), and fecal short-chain fatty acids (SCFAs) were measured in stool samples, by gas-liquid chromatography. RESULTS: In TEN patients, compared to controls (P < 0.01), aerobes were increased (8.46 +/- 0.24) while anaerobes were decreased (5.79 +/- 0.84). In TPN patients, both aerobes and anaerobes were decreased compared to controls (5.64 +/- 0.27 and 5.31 +/- 1.09 respectively, P < 0.01). Total SCFAs were lower in TPN patients than in TEN patients (48.3 +/- 16.6 vs 118.6 +/- 24.1 mmol/kg, P < 0.05). CONCLUSIONS: Both TPN and TEN induce modifications in the intestinal microflora. During TPN, a homogeneous decrease occurs in both aerobic and anaerobic bacteria. TEN decreases only anaerobic bacteria, while aerobic bacteria are increased. This imbalance may play a role in the pathophysiology of TEN-induced diarrhea.

Bacteria, Aerobic↗
PubMed2000

Characterization of delta-opioid receptors and effect of enkephalins on IRD 98 rat epithelial intestinal cell line.

Using 3H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (3H-DADLE) as a radioligand, delta-opioid binding sites on the IRD 98 rat epithelial cell line were identified. These sites were found to be reversible, saturable, specific and displayed high affinity for DADLE. Scatchard analysis revealed a dissociation constant (Kd) of 4.9+/-0.5 nmol/l, a maximum binding capacity (Bmax) of 1.7 pmol/mg protein, and 5x10(5) binding sites per cell. The presence of opioid receptors suggests the possibility that enkephalins directly control ion transport in enterocytes. In order to verify this hypothesis, investigations were designed to determine whether these receptors are functional and whether enkephalins can inhibit the stimulation of adenosine 3',5' cyclic monophosphate (cAMP) synthesis induced by cholera toxin. The increase in cAMP synthesis induced by cholera toxin was inhibited in a dose-dependent manner by H-Tyr-D-Ser-Gly-Phe-Leu-Thr-OH (DSLET), a delta-agonist. The enkephalinase inhibitor thiorphan potentiated this effect on IRD 98 cells, which contain enkephalinase. The action of DSLET was increased by 40% in the presence of this inhibitor. This effect was reversed by naltrindole, a potent delta-antagonist. Enkephalins can regulate intestinal secretion by acting directly on enterocytes: they thus have an antidiarrheal role, especially in the presence of an enkephalinase inhibitor.

Analgesics, Opioid↗
PubMed2000

Endoscopic bilateral metal stent placement for malignant hilar stenoses: identification of optimal technique.

BACKGROUND: The aim of this study was to identify factors that facilitate bilateral insertion of metal stents in malignant hilar stenoses, for which plastic stents often result in incomplete drainage and subsequent cholangitis. METHODS: Between January 1994 and April 1998, we collected 45 cases of advanced (Bismuth stage II or higher) hilar malignant stenoses. The insertion technique was progressively modified and the success rate in the early period (1994 to 1995) was compared with that of a later period (1996) and the most recent period (1997 to 1998). RESULTS: Overall success rate was 73.3% (33 of 45). The success rates for the three periods were 50%, 67%, and 88% (p = 0.008), respectively. Cholangitis occurred in 3 of the patients with unilateral stents compared with 1 with bilateral stents. CONCLUSION: We have described a technique for endoscopic insertion of bilateral metallic stents for malignant hilar stenoses that results in high (>88%) and reproducible success rates.

Aged↗
PubMed2000

Endoscopic management of sump syndrome after choledochoduodenostomy: retrospective analysis of 30 cases.

BACKGROUND: Side-to-side choledochoduodenostomy is a frequently performed operation. Postoperative biliary "sump syndrome" is infrequent, a complication for which endoscopic sphincterotomy is regarded as the treatment of choice. METHODS: We retrospectively analyzed 30 cases of sump syndrome and describe the symptoms, the delay before the appearance of symptoms, laboratory abnormalities, the nature of the biliary obstruction, and the outcome of endoscopic sphincterotomy including its efficiency and complications. RESULTS: The median clinical latency was 5 years (range 1 month to 28 years), the median delay between surgery and diagnosis was 6 years (range 1 month to 28 years). Fourteen patients had abdominal pain with fever, 5 had isolated abdominal pain, 4 had post-prandial pain, 4 had hepatic abscesses, and 3 had acute pancreatitis. Liver function tests were abnormal in 79%. During endoscopic retrograde cholangiopancreatography, food debris was identified in 18 patients in the biliary sump, biliary calculi in 10 patients, and a mixture of food and calculi in 2 patients. All patients underwent endoscopic sphincterotomy without complication. Recurrence during a median follow-up of 36 months (range 3 months to 11 years) was not observed. CONCLUSIONS: Sump syndrome most often becomes symptomatic only after a long delay. Abdominal pain with fever was the most frequent symptom. Liver function tests were abnormal in the majority of patients. Food debris was the most frequent cause. Endoscopic sphincterotomy appeared to be a safe, reliable treatment.

Adult↗
PubMed2000

Energy metabolism and substrate oxidation in patients with Crohn's disease.

Weight loss and malnutrition are common features in patients with Crohn's disease. This study was designed to evaluate diet-induced thermogenesis and substrate oxidation in patients with Crohn's disease. Twenty-three patients (17 women, 6 men; age 34 +/- 2 y) and 17 healthy control subjects (13 women, 4 men; age 36 +/- 3 y) were studied. Resting energy expenditure and fasting substrate oxidation were measured by indirect calorimetry in the morning after an overnight fast. After a standard homogenized test meal (10 kcal/kg), indirect calorimetry was performed every 30 min for 3 h to measure the diet-induced thermogenesis and the postprandial substrate oxidation. In the fasting state, resting energy expenditure was significantly higher in patients than in control subjects (1433 +/- 43 versus 1279 +/- 53 kcal/24 h). Lipid oxidation was higher in patients with Crohn's disease than in control subjects (1.17 +/- 0. 07 versus 0.61 +/- 0.11 mg. kg(-1). min(-1), P < 0.01). Postprandially, diet-induced thermogenesis was significantly lower in patients with Crohn's disease than in control subjects (4.6% +/- 0.5 versus 6.3% +/- 0.5 of energy intake, P < 0.01). Lipid oxidation was significantly higher in patients with Crohn's disease than in control subjects (0.78 +/- 0.05 versus 0.56 +/- 0.08 mg. kg(-1). min(-1), P < 0.05), and glucose oxidation was lower in patients with Crohn's disease than in control subjects. In patients with Crohn's disease, lipid oxidation positively correlates with the disease activity evaluated by the Crohn's Disease Activity Index (r = 0.48, P150), fasting and postprandial lipid oxidation was significantly higher than in patients with inactive Crohn's disease (P < 0.05). In conclusion, patients with Crohn's disease have increased fat oxidation, which correlates with disease activity and this may explain the reduced fat stores in patients with Crohn's disease.

Adult↗
PubMed2000

Resting energy expenditure in chronic hepatitis C.

BACKGROUND/AIMS: Hypermetabolism is considered to be of clinical interest in liver disease and in several chronic viral infections. Whether resting energy expenditure (REE) increases during chronic hepatitis C is not known. Our aims were: (a) to determine the metabolic state of patients with chronic hepatitis C, and (b) to evaluate the effects of interferon therapy on REE. METHODS: Forty-seven patients and 20 controls were studied. Sixteen patients failed to respond to interferon and 12 patients stopped the treatment during the first 2 months for various reasons. The 19 responders all received 1 year of interferon. REE (indirect calorimetry) and fat-free mass (FFM, bioelectric impedance analysis) were evaluated before (day 0) and after 90, 180, and 360 days of interferon. The virus load was evaluated in patients before treatment. RESULTS: On day 0, REE expressed as a ratio of FFM (REE/FFM) was higher in patients than in controls (129.2 +/- 14.7 vs 117.9 +/- 9.6 kJ kg FFM(-1) 24 h(-1), p<0.01), and was positively correlated with the viral load (r=0.45, p=0.01). On day 90, REE/FFM had significantly decreased in responders but it did not decrease in non-responders (p<0.01). In responders, REE/FFM on days 180 and 360 was similar to that of the controls. CONCLUSIONS: Chronic hepatitis C induces hypermetabolism that is normalized by interferon therapy in responders. The underlying mechanisms of chronic hepatitis C-induced hypermetabolism and its clinical relevance remain to be determined.

Adult↗
PubMed2000

Quality of life in long-term home enteral nutrition patients.

BACKGROUND AND AIMS: Few data are available on the quality of life of home enteral nutrition (HEN) patients. This study was designed to assess both the quality of life of long-term HEN patients and the evolution of quality of life after initiation of HEN. METHODS: Quality of life-related parameters were analysed in 38 patients (24M, 14F) aged 56 +/- 5 years who had been on HEN for more than 2 months (mean 25 +/- 5 months). Patients or close relatives were asked to answer a subjective assessment questionnaire, and patients with normal consciousness (n+ 24) answered the self-administered SF-36 and EuroQol questionnaires. RESULTS: Since the initiation of HEN, patients had spent 1.9 +/- 0.5% of the time in the hospital, in 54% of cases because of HEN-related complications. Analysis of the generic questionnaires revealed poorer quality of life parameters in comparison to a general population, although better results were sometimes observed in younger patients (under 45 years), patients without cancer, and patients with more than one care-giver. Nevertheless, the patients' subjective assessment of the changes in their quality of life since beginning HEN was generally good, with most patients reporting improved or stable mental and physical well-being. CONCLUSIONS: Quality of life is poor in HEN patients, but subgroups of patients who score better in some quality of life dimensions can be identified. Most patients describe an improvement in their quality of life following the initiation of HEN that needs to be confirmed by a prospective study.

Adaptation, Psychological↗
PubMed2000

Effects of 1-year interferon-alpha 2a treatment in patients with chronic hepatitis C and persistently normal transaminase activity.

BACKGROUND: Certain chronic hepatitis C carriers have persistently normal transaminase activity. The aims of this study were to determine the virologic and histologic effects of 1 year of interferon-alpha treatment in such patients. METHODS: Thirty-one patients were followed up in our Liver Unit. Eleven accepted interferon-alpha therapy; the 20 others were not treated and served as controls. Interferon-alpha, 3 MU, was given thrice weekly for 1 year. Serum was examined for hepatitis C virus (HCV)-RNA before, at the end of, and 6 months after treatment. Liver biopsy was performed 6 months after the cessation of treatment in 10 of 11 treated patients (one refused biopsy) and after a mean of 30.6+/-22.7 months in the 20 untreated patients. RESULTS: At the end of follow-up two of the treated patients had undetectable serum HCV-RNA and five had increased alanine aminotransferase (ALAT) values. In contrast, only one of the untreated patients had abnormal ALAT activity. All 20 untreated patients were constantly viremic. No significant histologic improvement was observed in the treated patients evaluated by means of post-treatment liver biopsy. The mean annual progression rate of fibrosis was very slow and similar in the treated and untreated patients (0.09 (range, 0-0.62) versus 0.07 (range, 0-0.60) fibrosis units). CONCLUSIONS: One year of interferon-alpha treatment can suppress HCV-RNA in patients with chronic hepatitis C and persistently normal ALAT values followed up over long periods. The rate of fibrosis progression in such patients is very slow, and therapeutic strategies should take this fact into account. Antiviral treatment is debated for patients without fibrosis in initial biopsy specimens.

Adult↗
PubMed2000

Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease.

OBJECTIVES: Chondrex (YKL-40) is a mammalian member of a protein family that includes bacterial chitinases. The pattern of its expression in certain tissues such as human liver or cartilage suggests a function in remodelling or degradation of extracellular matrix. The purpose of this study was to assess whether circulating YKL-40 might be a serum fibrosis marker in alcoholics. METHODS: Plasma YKL-40 was determined in 146 consecutive heavy drinkers (106 men, 40 women; mean age, 49.2 +/- 9.0 years). Liver biochemical parameters and serum fibrosis markers such as hyaluronate were also measured. Fibrosis and inflammation in liver biopsy were evaluated using a semi-quantitative scoring system. RESULTS: Plasma YKL-40 increased in parallel with the severity of fibrosis (P<0.00001). YKL-40 also increased in the presence of hepatic inflammation (P<0.01). Receiver operating characteristic curves of Chondrex revealed that a threshold of 330 microg/l gave a specificity of 88.5%; however, the sensitivity was only 50.8%. Only 11.5% of patients without severe fibrosis displayed a Chondrex plasma level above this threshold. A positive correlation was found between Chondrex and hyaluronate (r=0.40, P<0.0001), and a negative correlation was shown between Chondrex and the prothrombin index (r=-0.37, P<0.0001). CONCLUSIONS: The severity of liver fibrosis is associated with elevated circulating Chondrex levels. The overlap in YKL-40 values prevents use of Chondrex in a screening programme. High levels of Chondrex (above 330 microg/l) are predictive of severe liver fibrosis. Increased plasma YKL-40 may reflect the remodelling of liver fibrosis in alcoholics.

Adipokines↗
PubMed2000

Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells.

Use of the nonpathogenic yeast Saccharomyces boulardii in the treatment of infectious diarrhea has attracted growing interest. The present study designed to investigate the effect of this yeast on enteropathogenic Escherichia coli (EPEC)-associated disease demonstrates that S. boulardii abrogated the alterations induced by an EPEC strain on transepithelial resistance, [(3)H]inulin flux, and ZO-1 distribution in T84 cells. Moreover, EPEC-mediated apoptosis of epithelial cells was delayed in the presence of S. boulardii. The yeast did not modify the number of adherent bacteria but lowered by 50% the number of intracellular bacteria. Infection by EPEC induced tyrosine phosphorylation of several proteins in T84 cells, including p46 and p52 SHC isoforms, that was attenuated in the presence of S. boulardii. Similarly, EPEC-induced activation of the ERK1/2 mitogen-activated protein (MAP) kinase pathway was diminished in the presence of the yeast. Interestingly, inhibition of the ERK1/2 pathway with the specific inhibitor PD 98059 decreased EPEC internalization, suggesting that modulation of the ERK1/2 MAP pathway might account for the lowering of the number of intracellular bacteria observed in the presence of S. boulardii. Altogether, this study demonstrated that S. boulardii exerts a protective effect on epithelial cells after EPEC adhesion by modulating the signaling pathway induced by bacterial infection.

Apoptosis↗
PubMed2000

[Prevalence of hepatitis C in patients with chronic inflammatory bowel disease in the region of Nice and evaluation of risk factors].

OBJECTIVES: To estimate the prevalence of viral hepatitis C markers and to determine independent risk factors in a population of patients with inflammatory bowel disease. METHODS: We studied 117 consecutive out-patients (male/female, 53/64; mean age 41 +/- 16 yrs) with ulcerative colitis (43 patients) or Crohn's disease (74 patients). Anti-hepatitis C virus antibodies were tested with a third generation Elisa test. The following risk factors were tested for each patient: duration of inflammatory bowel disease, number of colonoscopies, history of surgical procedures, blood transfusions, intravenous drug abuse and immunosuppressive treatments. RESULTS: The seroprevalence of hepatitis C virus was 5.98% (7/117). The only risk factor independently associated with serological markers for hepatitis C virus was blood transfusion (odds ratio: 7.77; confidence interval: 95% (1.63-49.09); P=0.012). CONCLUSIONS: The prevalence of hepatitis C virus infection was high in patients with inflammatory bowel disease, mainly due to blood transfusions. Colonoscopies and surgical procedures were not found to be additional risk factors for infection with hepatitis C virus.

Adult↗