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Biomedical subjects

P Burtin

Publications and source records attributed to P Burtin.

At least 19 recordsLinked to original sources

Use of human skin equivalent Apligraf for in vitro assessment of cumulative skin irritation potential of topical products.

The main goal of the present study was to investigate the response of the human skin equivalent Apligraf in vitro to the application of irritant substances and its predictivity as a screening tool for cumulative skin irritant potential in humans. Vaseline, calcipotriol, trans-retinoic acid, and sodium lauryl sulfate were applied to Apligraf in vitro for 24 h. Cell viability (lactate dehydrogenase leakage), release and mRNA expression of the proinflammatory cytokines IL-1alpha and IL-8, and morphological changes were assessed. The same products were applied to 30 healthy volunteers in a double-blind, randomized, vehicle-controlled within-subject study. The skin reactions after repeated 24-h applications over 3 weeks under Finn chamber patches were monitored by visual scoring and biophysical methods (trans-epidermal water loss, chromametry, and blood flow). Sodium lauryl sulfate was cytotoxic to Apligraf, and increased the release and expression of cytokines at low (0.2%, 0. 4%), but not at high (0.8%, 1%) concentrations. It induced severe irritancy in vivo. Trans-retinoic acid increased the expression and release of cytokines with no detectable cytotoxicity and showed moderate irritancy in humans. Although calcipotriol did neither affect cell viability nor the production of cytokines, it induced morphological signs of irritation and was mildly irritant for healthy volunteers. Vaseline was innocuous in vivo and induced no changes in Apligraf. In conclusion, the cumulative skin irritation potential of the tested products could be predicted with Apligraf in a sensitive and specific manner, by monitoring cytotoxicity, proinflammatory cytokines, and morphological changes.

Double-Blind Method↗

[Nuclear magnetic resonance cholangiography in biliary disease. Prospective study in 60 patients].

PURPOSE: The aim of this prospective study was to evaluate a new MR cholangiography sequence, with thick slices, single shot fast spin echo (SSFSE) in biliary obstructive diseases. PATIENTS AND METHODS: This study included 60 patients (36 males and 24 females, mean age: 69 years) with cholestatic syndrome and suspected bile duct obstruction. All patients were prospectively investigated with MR cholangiography using SSFSE sequence with thick slices. The gold standard was ERCP (n = 47), per cutaneous cholangiography (n = 1), and surgical intervention (n = 12). According to this gold standard, 22 patients had obstructive gallstones, 23 had neoplastic obstruction, eight had inflammatory or postoperative stenosis and 7 had normal bile ducts. RESULTS: The sensitivity and specificity of MR cholangiography were 100 and 94% in the diagnosis of obstructive gallstones, and 95 and 97% in the diagnosis of neoplastic obstruction, respectively. A good agreement was observed between MR cholangiography and the gold standard, regardless of the site of obstruction (range of kappa value: 0.79-1). CONCLUSION: MR cholangiography with SSFSE sequence is an effective and easy technique. Acquisition of thick slices in a very short time (< 2 sec) limits cardiorespiratory artefacts and eliminates the need for post-processing.

Adult↗

Argon plasma coagulation for the treatment of hemorrhagic radiation proctitis.

BACKGROUND AND STUDY AIMS: Chronic radiation proctitis is a complication of radiotherapy for malignant pelvic diseases. Rectal bleeding caused by radiation proctitis is difficult to manage. Argon plasma coagulation (APC) is an electrocoagulation technique that appears to be an effective and low-cost alternative to the use of lasers in gastrointestinal endoscopy. The aim of this study was to evaluate the efficacy of APC, as well as patients' tolerance of the procedure, in the treatment of bleeding radiation-induced proctitis. PATIENTS AND METHODS: The charts of 16 patients with chronic radiation proctitis were analyzed retrospectively. Their average age was 73.5 (range 62-80). Fifteen patients had prostate cancer, and one had uterine cancer. The average time to onset of symptoms after radiotherapy was 15 months (range 6-36 months). All patients had intermittent or daily rectal bleeding, and three patients needed blood transfusions. The severity of bleeding was graded from 0 to 4. APC treatment was administered every month; the argon gas flow was set at 0.6 l/min with an electrical power setting of 40 W. RESULTS: All patients were improved with APC treatment. A mean of 3.7 sessions was necessary to relieve symptoms. APC therapy resulted in a reduction in the mean severity score from 2.4 to 0.6. Seven patients had no recurrent rectal bleeding, and the bleeding was significantly reduced to occasional and negligible spotting (less than one bleeding episode per week) in nine patients. None of the patients required transfusions after treatment. During the follow-up period (average 10.7 months, range 8-28 months), one patient had a recurrence of rectal bleeding that required two repeat sessions. The tolerance was good, with no long-term treatment-related complications. CONCLUSIONS: APC is an effective, safe and well-tolerated treatment for rectal bleeding caused by chronic radiation proctitis. It should be considered as a first-line therapy for radiation proctitis.

Aged↗

Predictivity of an in vitro model for acute and chronic skin irritation (SkinEthic) applied to the testing of topical vehicles.

An in vitro human reconstructed epidermis model (SkinEthic) used for screening acute and chronic skin irritation potential was validated against in vivo data from skin tolerability studies. The irritation potential of sodium lauryl sulfate (SLS), calcipotriol and trans-retinoic acid was investigated. The in vitro epidermis-like model consists of cultures of keratinocytes from human foreskin on a polycarbonate filter. The modulation of cell viability, the release and gene expression of proinflammatory cytokines, interleukins 1alpha and 8, and morphological changes were evaluated during 3 days as endpoints representative for an inflammatory reaction. The cumulative irritation potential of the topical products was evaluated in a human clinical study by visual scoring and biophysical measurement of inflammatory skin reaction after repeated 24 h applications over 3 weeks under Finn chamber patches. All topical products that were nonirritating in the human study were noncytotoxic and did not induce cytokine expression in the in vitro acute model (day 1 exposure). All irritating controls exhibited specific cell viability and cytokine patterns, which were predictive of the in vivo human data. The ranking of mild to moderate skin irritation potential was based on the lack of cytotoxicity and the presence of cytokine patterns including gene expression specific for each irritant, using the chronic in vitro model (up to 3 days exposure). The human reconstructed epidermis model SkinEthic was shown to be a reliable preclinical tool predicting the irritation potential of topical products. Moreover, it is a useful model in a two-step tiered strategy for screening acute and chronic irritation potential for the selection of vehicles for new topical drugs.

Adult↗

[Superficial stomach cancers: surgical experience and study of prognostic factors in 102 patients].

STUDY AIM: The aim of this retrospective study was to analyze the characteristics, treatment and prognosis of early gastric carcinoma in a series of 102 patients. METHODS: Between 1973 and 1994, 102 patients (68 males, 34 females) with a mean age of 65 years, were operated on for an early gastric carcinoma. Mean follow-up was 7 years. Survival was calculated using the Kaplan-Meier method. Prognosis was determined with univariate and multivariate analysis according to Cox model. RESULTS: The carcinoma was limited to the mucosa in 57 patients (56%) and extended to the submucosa in 45 (44%). There was a lymph node invasion in 17 patients (16.5%). The postoperative mortality rate was 5.8% (n = 6). Secondary deaths occurred in relation with the gastric cancer in 10.4% (n = 10). The 5- and 10-year actuarial crude survival rates were 84% and 68.6%, respectively. Univariate analysis of prognosis factors showed a significant survival difference according to the age (P = 0.001), submucosal extension (P = 0.03), lymph node invasion (P = 0.0005) and type of gastric resection performed (P = 0.03). With multivariate analysis of prognostic factors, advanced patient age and lymph node metastases were the only statistically significant independent prognostic factors, advanced patient age and lymph node metastases were the only statistically significant independent prognostic factors (P = 0.0002 and P = 0.002, respectively). CONCLUSIONS: Prognosis of early gastric cancer is usually excellent. Patients with high risk of recurrence may be identified in relation with prognostic factors and mainly with lymph node invasion.

Adult↗

Gastroesophageal endoscopic signs of cirrhosis: independent diagnostic accuracy, interassociation, and relationship to etiology and hepatic dysfunction.

BACKGROUND: The main objective of this prospective study was to evaluate the independent diagnostic accuracy of gastroesophageal endoscopic signs for cirrhosis. METHODS: Endoscopic signs were evaluated in vivo by one observer and on standardized videotape recordings by a consensus opinion of two endoscopists, with the stomach and esophagus examined both separately ("blind video") and together ("unblind video") in 168 consecutive patients with cirrhosis (n = 91), with non-cirrhotic liver disease (n = 29), and without liver disease (n = 48). The results were then tested in 149 different patients. RESULTS: Discriminant analysis of the "blind video" examination, considered to be the reference examination, showed that esophageal varices and portal hypertensive gastropathy had independent diagnostic accuracy (> or = 87%) for cirrhosis regardless of control group. However, in the "unblind video" and in in vivo examinations with different control groups, these results were altered. Prior knowledge of gastric patterns influenced the assessment of esophageal patterns. There was no independent association between portal hypertensive gastropathy or esophageal varices and the etiology of liver disease or the Child-Pugh score. CONCLUSIONS: When methodologic biases are eliminated, esophageal varices and portal hypertensive gastropathy have independent diagnostic accuracy for cirrhosis: esophageal varices had a diagnostic accuracy of 77% at the first step and increased to 89% with portal hypertensive gastropathy at the second step.

Adult↗

Metastatic gastric cancer arising from breast carcinoma: endoscopic ultrasonographic aspects.

Linitis plastica of the stomach was diagnosed in four patients. Endoscopic ultrasonography (EUS) was performed in four cases; they were monitored by EUS and had their treatment adapted accordingly. According to the present study, the typical criteria of gastric linitis at EUS are: (a) rigidity of the gastric wall; (b) a wall thickness exceeding 6 mm; (c) a second enlarged layer marginally more echogenic than the fourth hypoechogenic layer (muscularis propria); (d) a third hyperechogenic enlarged layer; and (e) a poor demarcation between layers. Gastric linitis appears more likely to be specific metastasis from lobular breast carcinoma. In most of the follow-up cases, EUS showed correlation with a subsequent decrease of the CA15.3 level. At present, EUS seems to be the most effective and least invasive examination for clinical diagnosis and treatment surveillance of secondary gastric linitis arising from infiltrating lobular carcinoma (ILC) of the breast.

Aged↗

Clinical relevance of therapeutic drug monitoring of digoxin and gentamicin in the saliva of children.

Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often difficult. In 11 children treated with digoxin for various cardiac conditions, and in 24 children treated with gentamicin (14 patients were administered gentamicin three times a day, and 10 once-daily), drugs levels were measured in plasma and saliva. There was no correlation between plasma total or free digoxin concentrations and saliva levels, precluding the clinical use of the saliva test for digoxin. No correlation was found between plasma gentamicin concentrations and saliva levels when the drug was administered three times a day; however, good correlation was found when the drug was administered once-daily (r2 = 0.89, p < 0.0001). Saliva may be used as a noninvasive method of measuring gentamicin serum concentrations to guide dosage adjustments in patients administered the drug once-daily.

Anti-Bacterial Agents↗

Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients.

PURPOSE: A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial. PATIENTS AND METHODS: Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined. RESULTS: A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase. CONCLUSION: Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.

Adenocarcinoma↗

[Prognostic value of Fürhman's grade in renal cell carcinoma. A study of 170 cases].

In order to evaluate the prognostic value of the anatomical stage (pTNM 1992) and of the histological factors (Führman's grade, cellular and architectural types), 170 renal cell carcinoma diagnosed between 1971 and 1991 were reviewed. In univariate analysis, the prognosis was correlated with the anatomical stage and Führman's grade: for the 125 patients without metastasis, grades 1 and 2 had a good prognosis, whereas grades 3 and 4 did poorly. The cellular type was not related to survival. Among architectural types, only the pseudo-sarcomatous type was correlated with prognosis. Multivariate analysis revealed that grade and metastasis at diagnosis were two independent predictors of survival; the grade was prognostically superior to metastasis. Führman's grade is essential in determining prognosis; its statistical value is superior to anatomical stage in multivariate analysis.

Adult↗

[Evaluation of a new MRI cholangiography sequence with a half-Fourier acquisition technic].

PURPOSE: The aim of this study was to evaluate a new MR cholangiography sequence in which thick slices are obtained with half Fourier acquisition (SSFSE) in biliary obstructive diseases. PATIENTS AND METHODS: Fifty patients with suspected bile duct obstruction were prospectively investigated with MR cholangiography using SSFSE sequence with thick slices. The gold standard was ERCP (n = 40), percutaneous cholangiography (n = 1) or surgical findings (n = 9). According to this gold standard, 17 patients had bile duct lithiasis and 21 had neoplastic obstruction. RESULTS: The sensitivity and specificity of MR cholangiography were 100% and 94% for the diagnosis of lithiasis obstruction and 95% and 97% for neoplastic obstruction. Agreement between the MR cholangiogram and the gold standard was good whatever the site of obstruction (range of kappa values: 0.79-1). CONCLUSION: MR cholangiography with SSFSE sequence is a useful, precise and easy to use technique. Acquisition time for thick slices is short (< 2 sec) limiting cardiorespiratory artefacts and eliminating the need for post-treatment.

Adult↗

Endoscopic detection of early esophageal cancer in a high-risk population: does Lugol staining improve videoendoscopy?

BACKGROUND: The aim of this study was to prospectively compare the diagnostic accuracy of videoendoscopy, with and without Lugol staining, for the detection of esophageal cancer in alcoholic or smoking patients older than 40 years. METHODS: Daily alcohol and tobacco consumption and overt and latent symptoms were noted. The 158 patients included were examined by videoendoscopy and with Lugol dye. RESULTS: The mean consumption of alcohol and tobacco was 86 +/- 49 gm/day for 26 +/- 11 years, and 30 +/- 18 pack-years, respectively. Twenty-five patients had no symptoms. Before Lugol staining, 12 patients had endoscopically identified cancerous lesions. After Lugol staining, 13 patients had 17 esophageal cancers, 3 of which were high-grade dysplasia. The prevalence of esophageal cancer was 8.2%: 95% CI [4,14]. Dye-free surfaces were significantly larger than the endoscopic patterns observed before Lugol staining (11.6 +/- 9.2 cm2 vs 1.4 +/- 1.7 cm2; p < 0.02). CONCLUSIONS: In an alcoholic smoking population, the prevalence of esophageal cancer detected by endoscopy is high and not related to symptoms described by patients. Lugol staining only moderately improves the diagnostic accuracy of videoendoscopy; its main advantage is the assessment of the mucosal extension of esophageal cancer.

Adult↗

Interobserver agreement on endoscopic diagnosis of bleeding peptic ulcers.

BACKGROUND: The aim of this prospective study was to evaluate the interobserver agreement of stigmata of recent hemorrhage of bleeding peptic ulcers. METHODS: Sixty-one consecutive adult patients were enrolled in the study and nine (three junior and six senior) endoscopists reviewed standardized video recordings of endoscopic examinations. Interobserver agreement was evaluated using the kappa (kappa) index, intraclass correlation coefficient, and proportion of agreement. Observer bias and poorly trained observers were investigated. RESULTS: Interobserver agreement was very good for oozing (kappa = 0.68), good for clot (kappa = 0.51), poor for spurting (kappa = 0.29) and visible vessels (kappa = 0.33), and excellent for the absence of stigmata (kappa = 0.82). Observer bias sometimes occurred and the number of poorly trained observers was low. The kappa indexes were significantly better in senior than in junior investigators: 0.48 +/- 0.16 versus 0.37 +/- 0.26, respectively, p < 0.05. The agreement between the in vivo evaluation and video tape recordings (intraobserver agreement) was good (kappa = 0.60 +/- 0.19). There was no training phenomenon between the first and the second half of the patient group. CONCLUSIONS: The endoscopic classification of bleeding ulcers might be simplified by limiting grading to a few classes. Special attention should be paid to the training of endoscopists.

Adult↗