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Biomedical subjects

P Denis

Publications and source records attributed to P Denis.

At least 55 records · Page 3Linked to original sources
PubMed2002

The effect of cholecystectomy on duodenojejunal motility in humans.

We hypothesized that certain gastrointestinal symptoms following cholecystectomy could be explained by motor disturbances. To test this hypothesis, we compared pre- and post-operative motor patterns between symptomatic and asymptomatic patients after surgery to evaluate whether some motor changes could be induced by gallbladder removal and associated with symptoms. Twenty-three patients were prospectively evaluated before and 3 months after cholecystectomy. After surgery, 17 patients were asymptomatic and six were symptomatic. Duodenojejunal manometric recordings were performed for 3 h during fasting, then 3 h after a 750-kcal meal. Patient motor results were compared to those obtained in the duodenojejunum of 20 healthy controls. After surgery, only a few modifications in duodenojejunal motility were observed compared to the preoperative period. Motor changes related to cholecystectomy were increase in phase III amplitude and the absence of progressive decrease of the duodenojejunal motor response after the meal. After surgery, symptomatic patients had a lower postprandial duodenal motility index after the meal than asymptomatic patients (P < 0.03) and more frequent propagated clusters of contractions (PCCs) (P < 0.02). Preoperative motor patterns associated with postoperative symptoms were postprandial only and included a low duodenal motility index (P < 0.03), and a higher number of PCCs (P < 0.02). Removal of the gallbladder has a limited effect on duodenojejunal motility. Few motor differences existed between symptomatic and asymptomatic patients after surgery. However, a low duodenal motor response to a meal and PCCs were often associated with symptoms.

Area Under Curve↗
PubMed2002

Does water-perfused catheter overdiagnose anismus compared to balloon probe?

BACKGROUND: The purpose of this study was to compare the manometric assessment of straining effort as if to defecate and rectoanal inhibitory reflex obtained with a rectosphincteric balloon probe and with a water-perfused catheter in the same subject. METHODS: Twelve healthy volunteers underwent two manometric assessments of anal sphincter function and electromyographic (EMG) surface recordings. one with a rectosphincteric balloon and one with a water-perfused catheter, 7 days apart in random order. RESULTS: Increased EMG activity in the external anal sphincter in the midst of the rectoanal inhibitory reflex (P < 0.001) and during straining for defecation (P < 0.001) was more frequently observed with the perfused system than with the balloon probe. There was a discrepancy between the EMG activity of the external anal sphincter and the anal pressures during straining recorded with the perfused system. Duration of the reflex elicited by rectal distension with 10 and 20 ml of air was significantly greater with the rectosphincteric balloon than with the perfused catheter (P = 0.02 and P = 0.05, respectively). CONCLUSION: Water instilled in the anal canal by the perfused system induces artifacts in EMG recording and active anal contractions. These artifacts and induced contractions could lead to an erroneous diagnosis of anismus, particularly if pelvic floor EMG is only taken into account for the diagnosis of anismus.

Adult↗
PubMed2002

[Creating a specific quality-of-life questionnaire in patients with glaucoma: item generation].

The methods for developing Health-Related Quality-of-Life (HRQoL) measures and their application in medical research have demonstrated their utility in various chronic, progressive, or life-threatening diseases. The efforts made to allow the patient's perspective to be included in the methodological framework of evidence-based medicine have been successful. The assumption of a strong relationship between clinical status and daily life is certainly valid in ophthalmology. However, there is a lack of specific HRQoL measures dedicated to ophthalmic diseases. Our work aimed at creating the first Glaucoma-specific Quality of Life scale - the Glau-QoL questionnaire - to provide researchers and physicians with a comprehensive, practical, and validated tool. This article describes the first stage of the process, which consisted in generating items and formatting them in order to create a questionnaire that exhaustively covers the relevant concepts. The whole process was conducted by an expert committee including clinicians and methodologists. The standard recommendations in the development of a HRQoL questionnaire were followed: we first identified existing tools and performed a preliminary collection of concepts from the published literature; we then designed an interview guide with the help of clinicians; a trained psychologist interviewed 22 patients at various disease severity stages (from isolated hypertonic to severely impaired); the interviews were tape-recorded and scripted; general domains and related detailed concepts were identified from the script; they were then analyzed and organized; the format of the questionnaire was set up; and questions were derived from the patient's verbatim to capture the identified detailed concepts. The test questionnaire was applied to seven patients for cognitive debriefing. We finally amended the test questionnaire and designed the pilot questionnaire according to the patients' tests and the clinician's review. The test questionnaire was well accepted by the patients, despite a completion duration ranging from 14 to 35 minutes. The pilot questionnaire contained 151 items, grouped into 5 sections: (1) vision problems, physicians, and daily treatment (49 items); (2) activities of daily living (37 items); (3) self-expression (37 items); (4) vision problems and mood (14 items); and (5) other questions (14 items). The next step of our work will be the item reduction process and the psychometric validation of the Glau-QoL questionnaire.

Activities of Daily Living↗
PubMed2001

Esophageal involvement and pulmonary manifestations in systemic sclerosis.

OBJECTIVE: To assess whether esophageal manometric motor disturbances are associated with abnormalities consistent with interstitial lung disease (ILD) on both pulmonary function tests (PFT) and high resolution computerized tomography (HRCT) scans in patients with systemic sclerosis (SSc), during initial evaluation and at 2 years followup. METHODS: Esophageal manometry, PFT, and HRCT scans were performed in 43 consecutive SSc patients. PFT and HRCT scan parameters were compared between patients with severe esophageal motor dysfunction (i.e., aperistalsis and decreased low esophageal sphincter pressure), patients with moderate esophageal motor dysfunction (hypoperistalsis), and patients without esophageal motor dysfunction on manometry. RESULTS: During initial evaluation of SSc, patients with severe esophageal motor impairment, compared with those with moderate and without esophageal dysmotility, exhibited significantly decreased median values of diffusing capacity for carbon monoxide (DLco) (68% vs. 94% vs. 104%) and exhibited higher prevalence of evidence for ILD on HRCT scan (57% vs. 27% vs. 18%). At 2 years followup of SSc, patients with severe esophageal motor disturbances, compared with those without, had faster deterioration of DLco median values (-16% vs. +1%) and higher frequency of ILD on HRCT scan (70% vs. 25%). CONCLUSION: Our series underscores a correlation between the degree of esophageal manometric motor disturbances and evidence for ILD on PFT and HRCT scan in SSc patients, suggesting that gastroesophageal reflux (GER) may be one of the contributing factors of ILD in SSc. Our findings further indicate that patients with severe esophageal impairment may require closer followup of lung parameters. In turn, it suggests that aggressive therapy of GER should be initiated in these SSc patients, as it may result in decreased deterioration of pulmonary function.

Adult↗
PubMed2001

Effect of sacral nerve stimulation in patients with fecal and urinary incontinence.

PURPOSE: Preliminary studies have shown improvement in fecal incontinence in several patients who received temporary or permanent stimulation. The purpose of this study was to report our experience in sacral nerve stimulation in the treatment of fecal incontinence and to target patients who would benefit most from stimulation. METHODS: Patients with fecal incontinence were studied clinically and manometrically before, during, and after temporary nerve stimulation. If temporary nerve stimulation was clinically successful, the patient was implanted and followed up for six months. RESULTS: Nine patients (6 female) with a mean age of 50.7 +/- 12.3 years underwent temporary nerve stimulation. Temporary nerve stimulation was successful in eight patients, six of whom were implanted. Of the patients who could be evaluated, three of five had improved at the six-month follow-up visit, particularly in relation to the number of urgency episodes and delay in postponing defecation. All implanted patients had urinary symptoms. Urinary urgency was also improved by stimulation. During temporary nerve stimulation, the maximal squeeze pressure amplitude increased. After implantation, only the duration of maximal squeeze pressure seemed to improve. CONCLUSION: Sacral nerve stimulation can be used in the management of fecal incontinence, particularly in cases of urge fecal incontinence associated with urinary urgency. This study seems to confirm the effect of sacral nerve stimulation on striated sphincter function.

Adult↗
PubMed2001

Additive IOP-reducing effect of latanoprost in patients insufficiently controlled on timolol.

PURPOSE: To evaluate the effect on intraocular pressure (IOP) of switching from timolol to latanoprost or adding latanoprost to timolol in patients with open angle glaucoma or ocular hypertension where IOP is not adequately controlled with timolol. METHODS: This was a 6-week, double-masked, randomised multi-centre study. 53 patients with primary open angle glaucoma, capsular glaucoma, or ocular hypertension with an IOP of at least 21 mmHg on current therapy were recruited. After a run-in period of at least 2 weeks on timolol, 5 mg/ml twice daily, patients were randomised to one of three groups. One group continued on timolol, one switched from timolol to latanoprost, 50 microg/ml once daily, and a third group received latanoprost in addition to timolol. The efficacy was evaluated by comparing IOP at 9 AM at baseline and after 6 weeks of treatment. RESULTS: IOP at baseline and after 6 weeks of treatment (mean +/- SEM) were 24.2 +/- 0.9 and 23.8 +/- 1.0 mmHg (n = 16) for patients continuing on timolol, 26.3 +/- 1.2 and 19.6 +/- 1.1 mmHg (n = 17) for patients switching to latanoprost, and 23.2 +/- 1.0 and 17.5 +/- 0.8 mmHg (n = 17) for patients with combined treatment. Adding latanoprost to timolol reduced IOP with 5.9 +/- 0.9 mmHg (p < 0.001) and switching from timolol to latanoprost reduced IOP with 5.0 +/- 0.9 mmHg (p < 0.001), which caused in each group a significant IOP reduction of about 25%. CONCLUSIONS: The effect of latanoprost was additive to that of timolol, and a good effect on IOP reduction was also achieved by switching from timolol to latanoprost, suggesting that a switch in many patients is an effective alternative to combination treatment.

Adult↗
PubMed2001

Does the supplementation of the formula with fibre increase the risk of gastro-oesophageal reflux during enteral nutrition? A human study.

BACKGROUND & AIMS: Fibre-supplements in enteral feeding could increase the risk of gastro-oesophageal reflux (GOR). The aim of this study was to assess in humans the physiological effects of the supplementation of the enteral diet with different types of dietary fibre on gastro-oesophageal reflux episodes, gastric acidity and gastric emptying. METHODS: pH profiles were compared in 12 healthy volunteers between three different formula (500 kcal, 250 mL x h-1) delivered in a random order and containing either no fibre, either soy polysaccharide fibre only or mixed fibre from pea and inuline. Enteral diets were instilled through a nasogastric tube. Oesophageal and gastric pH recordings were combined with the ultrasound measurement of gastric antral area during the infusion. RESULTS: More GOR were observed with a fibre-free diet (median 4, range 1-10) than with a mixed (median 1.5, range 0-5) (P=0.04) or soy polysaccharide fibre (median 1.5, range 0-5) (P=0.04) diet. The median duration of GOR was longer with the mixed fibre (median 3.6, range 1.8-7.2) than with the fibre-free diet (mean 1.8 min, range 1-3.6) (P<0.05). The number of GOR episodes lasting more than 5 min, the duration of the longest GOR and the percent of time under pH 4 were not significantly different with the three diets. The intragastric pH profile and the ultrasound antral area were not different with all three diets. CONCLUSIONS: Addition of fibre to the enteral formula had limited effects on the onset of GOR episodes. It decreased the number of GOR but increased their duration. These effect were more pronounced with the formula containing soluble fibre. At variance, the addition of fibre had no significant effect on gastric emptying and gastric acid secretion.

Adult↗
PubMed2001

Effects of polyethylene glycol 4000 on 24-h manometric recordings of left colonic motor activity.

BACKGROUND: It has been shown that low doses of polyethylene glycol (PEG) 4000 are effective in the treatment of chronic constipation. The aim of this study was to describe the effects on colonic motility of oral PEG 4000 treatment and intraluminal instillation of PEG 4000. METHODS: Left colonic and rectosigmoid manometric recordings were performed for 27 h in six constipated patients and in six healthy volunteers. At the end of the recording, bisacodyl and PEG 4000 were instilled into the lumen of the colon. To assess the effects of oral administration of PEG 4000 on colonic motility, manometric recordings were also performed in constipated patients after 4 weeks of treatment with PEG 4000. RESULTS: All patients had significantly more stools during than before PEG treatment. There was no significant difference between the number and the characteristics of high-amplitude propagating contractions (HAPC) or the area under the curve (AUC) before or during treatment with PEG 4000. Intraluminal instillation of PEG induced HAPC in only one patient and in no controls. CONCLUSION: This study shows that PEG 4000 has no effect on left colonic and rectosigmoid motor activity during oral treatment, despite its clinical effectiveness, or after local instillation.

Administration, Oral↗
PubMed2001

Gastric involvement in systemic sclerosis: a prospective study.

OBJECTIVES: This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances. METHODS: Fasting and postprandial gastric electrical activity was studied in 22 consecutive patients with SSc (17 with and 5 without clinical gastric manifestations) and 22 age- and sex-matched healthy subjects. Gastric emptying of radiopaque pellets and gastroscopy were also performed in SSc patients. RESULTS: The prevalence of EGG disturbances was as high as 81.82% in SSc patients. SSc patients exhibited, compared with controls, higher median percentage of dominant frequency in bradygastria during the fasting period and lower median values for postprandial electrical power and postprandial to fasting ratio for electrical power. Gastric emptying of radiopaque pellets was delayed in 11 SSc patients, and gastroscopy demonstrated "watermelon stomach" in 3 SSc patients. No correlation was found between the severity of gastric impairment and clinical presentation, SSc duration and subsets, and esophageal manometric impairment. CONCLUSIONS: Our study underlines the high frequency of gastric dysfunction in SSc patients. It suggests the usefulness of EGG in SSc in noninvasively detecting disorders of gastric electrical activity at an early stage and symptomatic patients with gastroparesis (because there was a correlation between values of postprandial to fasting ratio for electrical power of < 1 on EGG and delayed gastric emptying). Gastric-emptying evaluation of radiopaque pellets may further be a helpful method to depict symptomatic SSc patients with gastroparesis. Finally, our series confirms that watermelon stomach diagnosis should be excluded in SSc patients presenting with gastrointestinal hemorrhage or with anemia related to iron deficiency.

Adult↗
PubMed2001

[Conjunctival epithelial carcinoma in a 9-year-old child with xeroderma pigmentosum. Case report].

We report the case of a conjunctival tumor in a 9-year-old patient, suffering from Xeroderma Pigmentosum. Our patient presented a raspberry-colored conjunctival tumor. The tumor was resecked without any additional treatment. The histological study revealed squamous cell carcinoma. A suspicion of relapse appeared two months later of the same location and a new resection was performed. The initial checkup of this tumor was negative. In this disease, ocular localizations are frequent. The conjunctiva, the cornea, the eyelids and, into a lesser extent, the orbit can be involved. Basal cell carcinoma and squamous cell carcinoma are the most frequent tumors observed in Xeroderma Pigmentosum. Their treatment is mainly surgical.

Carcinoma, Squamous Cell↗
PubMed2000

A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's beta -secretase.

The novel transmembrane aspartic protease BACE (for Beta-site APP Cleaving Enzyme) is the beta-secretase that cleaves amyloid precursor protein to initiate beta-amyloid formation. As such, BACE is a prime therapeutic target for the treatment of Alzheimer's disease. BACE, like other aspartic proteases, has a propeptide domain that is removed to form the mature enzyme. BACE propeptide cleavage occurs at the sequence RLPR downward arrowE, a potential furin recognition motif. Here, we explore the role of furin in BACE propeptide domain processing. BACE propeptide cleavage in cells does not appear to be autocatalytic, since an inactive D93A mutant of BACE is still cleaved appropriately. BACE and furin co-localize within the Golgi apparatus, and propeptide cleavage is inhibited by brefeldin A and monensin, drugs that disrupt trafficking through the Golgi. Treatment of cells with the calcium ionophore, leading to inhibition of calcium-dependent proteases including furin, or transfection with the alpha(1)-antitrypsin variant alpha(1)-PDX, a potent furin inhibitor, dramatically reduces cleavage of the BACE propeptide. Moreover, the BACE propeptide is not processed in the furin-deficient LoVo cell line; however, processing is restored upon furin transfection. Finally, in vitro digestion of recombinant soluble BACE with recombinant furin results in complete cleavage only at the established E46 site. Taken together, our results strongly suggest that furin, or a furin-like proprotein convertase, is responsible for cleaving the BACE propeptide domain to form the mature enzyme.

Alzheimer Disease↗
PubMed2000

Characterization of Alzheimer's beta -secretase protein BACE. A pepsin family member with unusual properties.

The cerebral deposition of amyloid beta-peptide is an early and critical feature of Alzheimer's disease. Amyloid beta-peptide is released from the amyloid precursor protein by the sequential action of two proteases, beta-secretase and gamma-secretase, and these proteases are prime targets for therapeutic intervention. We have recently cloned a novel aspartic protease, BACE, with all the known properties of beta-secretase. Here we demonstrate that BACE is an N-glycosylated integral membrane protein that undergoes constitutive N-terminal processing in the Golgi apparatus. We have used a secreted Fc fusion-form of BACE (BACE-IgG) that contains the entire ectodomain for a detailed analysis of posttranslational modifications. This molecule starts at Glu(46) and contains four N-glycosylation sites (Asn(153), Asn(172), Asn(223), and Asn(354)). The six Cys residues in the ectodomain form three intramolecular disulfide linkages (Cys(216)-Cys(420), Cys(278)-Cys(443), and Cys(330)-Cys(380)). Despite the conservation of the active site residues and the 30-37% amino acid homology with known aspartic proteases, the disulfide motif is fundamentally different from that of other aspartic proteases. This difference may affect the substrate specificity of the enzyme. Taken together, both the presence of a transmembrane domain and the unusual disulfide bond structure lead us to conclude that BACE is an atypical pepsin family member.

Amino Acid Sequence↗
PubMed2000

Results of sphincteroplasty in 86 patients with anal incontinence.

PURPOSE: This study was designed to analyze critically the short-term and long-term outcome of sphincteroplasty and to identify high-risk factors. METHODS: Eighty-six patients with fecal incontinence associated with an ultrasound defect of the external anal sphincter were treated by anal sphincteroplasty. Clinical and physiologic assessment was made before surgery, and clinical evaluation was made three months and an average of 40 months after surgery. RESULTS: The evaluation of 86 patients three months after surgery showed that 42 patients were totally continent (49 percent), 28 were incontinent for gas (33 percent), and 16 still had fecal incontinence (19 percent). Seventy-four patients (86 percent) were contacted 40 months after surgery. Twenty-one patients (28 percent) were totally continent, 17 were incontinent to gas (23 percent), and 36 were incontinent to feces (49 percent). Forty-six percent of patients felt they were clearly improved after surgery. Poor results were associated with an internal anal sphincter defect. CONCLUSIONS: Our study suggests that in the long term, one-third of patients are totally continent after sphincteroplasty. One-half of patients are satisfied, but only if their incontinence to feces has totally disappeared. Results of sphincteroplasty deteriorate with time. One factor in poor prognosis is the presence of an associated defect of the internal anal sphincter.

Adult↗
PubMed2000

[Is cognitive change related to hypothyroidism reversible with replacement therapy?].

PURPOSE: Although cognitive impairment related to hypothyroidism has been investigated, issues regarding treatment have been less extensively studied. The aim of this study was to assess cognitive function in patients with hypothyroidism just before treatment and after hypothyroidism had resolved. METHODS: Standardized psychometric assessment (including ten tests) was done in 30 outpatients with biochemical evidence of hypothyroidism (TSH = 92.1 mU/L, range: 11.4-400) and in 30 control subjects matched for age and gender with normal thyroid function. These tests were repeated twice before treatment and after hypothyroidism had been cured. Statistical analysis was done using the Mann-Whitney U test. RESULTS: The baseline characteristic of patients with hypothyroidism showed that attention, motor speed, memory and visual-spatial organization were significantly impaired. Cognitive decline was significantly greater with increasing age. Cognitive impairment significantly decreased after hypothyroidism had been cured, reaching values obtained in age-matched control subjects. CONCLUSION: Attention, motor speed, memory and visual-spatial organization are significantly impaired in hypothyroidism, particularly in the elderly, suggesting that ageing could have potential effects on cognitive functions. Hormone-replacement therapy leads to normalization of the cognitive functions.

Age Factors↗