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Biomedical subjects

P Roy

Publications and source records attributed to P Roy.

At least 19 recordsLinked to original sources

Structural and thermal characterization of glyceryl behenate by X-ray diffraction coupled to differential calorimetry and infrared spectroscopy.

Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as sustained-release matrix in pharmaceutical applications are studied by coupled time-resolved synchrotron X-ray diffraction and Differential Scanning Calorimetry combined with Infrared Spectroscopy. With these techniques, all polymorphs formed in glyceryl behenate, analyzed as received and after various thermal treatments from quenching to slow crystallization, are characterized. By using different well-controlled mixtures of mono-, di- and tribehenate, we identify each lamellar phase observed in the glyceryl behenate. Finally the influence of the crystallization rate on the formation of preferential conformations was also analyzed in order to bring insights into the polymorphism of glyceryl behenate. By changing the crystallization rate of the sample, it was shown that one can favor the formation of preferential polymorphs in the sample. In particular the crystallization at 10 degrees C/min seems to be well adapted for producing a single lamellar phase with a period of 60.9 A while a crystallization rate of 0.4 degrees C/min produces three different lamellar phases.

Calorimetry, Differential Scanning↗

Extensive multiallelic analysis of the relationship between HLA-DRB1 and rheumatoid arthritis using a Bayesian partition model.

To analyse the association between individual HLA-DRB1 locus genotypes and rheumatoid arthritis (RA) susceptibility, taking in account the multiallelic nature of the shared epitope (SE). In total, 538 patients and 536 controls were genotyped for 12 alleles of the HLA-DRB1 locus. A Bayesian partition model and multivariate logistic models were used to assess the role of the SE and of its individual components. The SE was associated with RA susceptibility (odds ratio (OR) 2 versus 0 SE copy=9.99 (95 CI 4.69-15.30) and OR 1 versus 0 SE copy=3.16 (95% CI 2.42-4.12)). The Bayesian partition model supplied a permutation of the HLA-DRBA locus alleles ordered by increasing disease risk. Alleles associated with highest risks are those that code for the SE. The individual OR estimations for the HLA-DRB1 locus genotypes went from OR=1.00 (95% CI 1.00-1.25) for the less associated genotype to OR=21.40 (95% CI 8.02-65.79) for the most associated one. In conclusion, the allele order risk and the OR estimations for individual genotypes of the HLA-DRB1 locus were consistent with the SE theory. Using an exploratory statistical method without a priori hypothesis, our study allowed a detailed analysis of the multiallelic nature of the SE.

Adult↗

Bluetongue virus assembly and morphogenesis.

Like other members of the Reoviridae, bluetongue virus faces the same constraints on structure and assembly that are imposed by a large dsRNA genome. However, since it is arthropod-transmitted, BTV must have assembly pathways that are sufficiently flexible to allow it to replicate in evolutionarily distant hosts. With this background, it is hardly surprising that BTV interacts with highly conserved cellular pathways during morphogenesis and trafficking. Indeed, recent studies have revealed striking parallels between the pathways involved in the entry and egress of nonenveloped BTV and those used by enveloped viruses. In addition, recent studies with the protein that is the major component of the BTV viroplasm have revealed how the assembly and, as importantly, the disassembly of this structure may be achieved. This is a first step towards resolving the interactions that occur in these virus 'assembly factories'. Overall, this review demonstrates that the integration of structural, biochemical and molecular data is necessary to fully understand the assembly and replication of this complex RNA virus.

Animals↗

How to approach drug-eluting stent restenosis.

Drug-eluting stents (DES) have been a major advance in percutaneous coronary intervention reducing restenosis and repeat revascularization. The application of DES to the treatment of complex lesion and patient subsets has resulted in significant rates of DES restenosis or failure. Though predominantly focal, substantial rates of non-focal DES restenosis are being observed. Non-focal disease most likely represents a resistant process that will remain a therapeutic challenge. An understanding of the causative mechanical and biological factors is essential for the prevention and treatment of DES restenosis. Robust data relating to the treatment efficacy for this problem is lacking. At present, repeat DES or vascular brachytherapy appear to the best available options. Evidence from randomized controlled trials and large registries is required to establish a formal treatment approach. We provide guidelines based on current available evidence.

Coronary Restenosis↗

Signatures of the hydrogen bonding in the infrared bands of water.

Infrared spectroscopy measurements have been completed over a wide range of frequencies allowing to measure the evolution of both intramolecular and intermolecular vibrational modes in water as a function of temperature. Emphasis is made on the high frequency OH stretching band and the so-called connectivity band that lies in the far infrared region. The substructures of the two infrared bands are analyzed in terms of different levels of connectivity of the water molecules, along the statements of the percolation model. Both band profiles appear to be related to the different degrees of connectivity of water molecules. Comparison of the data with the predictions of the percolation model shows good agreement as for the temperature evolution of liquid water. This work provides additional support to the interpretation of water bands substructures as signatures of its very specific connectivity pattern.

Journal Article↗

A randomised, double-blind, parallel, placebo-controlled study to evaluate the efficacy of MF 5232 (Mucotrol), a concentrated oral gel wafer, in the treatment of oral mucositis.

OBJECTIVE: Oral mucositis is a major complication of cytotoxic chemotherapy and radiotherapy associated with significant morbidity, pain, odynophagia, dysgeusia and subsequent dehydration and malnutrition, and effective prophylaxis and/or treatment of this condition is essential. The currently available palliative treatment shows improvement only in patients with mild to moderate mucositis. The primary aim of this study was to compare the clinical efficacy of MF 5232 (Mucotrol), a concentrated oral polyherbal gel wafer formulation, with placebo in the management of chemoradiation-induced mucositis in cancer patients. PATIENTS AND DESIGN: In this randomised, double-blind, pilot study a total of 30 patients of either sex with chemoradiation-induced oral mucositis were randomised to receive MF 5232 (n = 15) or a matching placebo (n = 15) after food three times a day for 7-10 days. Patients were evaluated using validated and standardised scoring systems at baseline and after 7-10 days of treatment. RESULTS: There were 11 evaluable patients in each treatment group. There was a significant reduction in mean mucositis scores with MF 5232 as follows: WHO (from 3.0 to 1.8), Radiation Therapy Oncology Group (gross score: from 2.8 to 1.8; functional score: from 2.9 to 1.0), and Objective Scoring System (ulceration score: from 7.4 to 4.4; erythema score: from 13.7 to 7.0). There were no significant changes in scores for placebo recipients. The treatments were well tolerated, with the exception of two patients in the treatment group who reported a burning sensation in the mouth after dissolving the wafer. CONCLUSION: This pilot study provided positive evidence for the efficacy of MF 5232 therapy in chemoradiation-induced mucositis. This was probably a result of its local analgesic, antioxidant and immunomodulatory activity and wound-healing properties. Further in-depth analysis in a larger number of patients is required to confirm these positive results.

Administration, Oral↗

The single-dose pharmacokinetics of the novel CCK1 receptor antagonist, dexloxiglumide, are not influenced by age and gender.

OBJECTIVE: The effects of age and gender on the single-dose pharmacokinetics of dexloxiglumide, a selective cholecystokinin (CCK1-subtype) receptor antagonist, were assessed in healthy young and elderly male and female subjects. METHODS: In total, 24 males and 24 females (12 young and 12 elderly subjects per gender group) received a single oral dose of 200 mg dexloxiglumide under fasted conditions. Mean (range) ages were 23.8 (18 - 32) and 71.3 (66 - 88) years for young and elderly subjects, respectively. Analysis of covariance (ANCOVA) with age group and gender as factors and body weight as a covariate was performed on the dexloxiglumide pharmacokinetic parameters of peak plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC). The p values obtained from ANCOVA were considered for the assessment of age and gender effects. RESULTS: A small (approximately 18%) but statistically significant (p < or = 0.036) increase in the area under the plasma concentration-time curve from 0 to time of last quantifiable concentration (AUC(0-t) and the area under the plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) in elderly compared to young subjects was noted. Given the lack of age effects on the other pharmacokinetic parameters of dexloxiglumide, this limited difference is unlikely to be clinically relevant. Without the adjustment for body weights, female subjects exhibited mean C(max) and AUC values approximately 26% and 36% higher than male subjects; however, these exposure differences did not reach statistical significance (p > 0.05) following ANCOVA analysis with body weight as a covariate. Likewise, there were no statistically significant differences (p > 0.05) observed for any other pharmacokinetic parameters between young and elderly and between male and female groups. CONCLUSIONS: Dose adjustments based on age and gender are not necessary. Dexloxiglumide administration was safe and well tolerated in these subjects.

Adolescent↗

Nucleotide sequence analysis of the L1 loop variable region of hexon gene of fowl adenovirus 4 isolates from India.

Three fowl adenovirus 4 (FAV4) isolates from chicken and one from quail, all from Tamil Nadu, India were analyzed. The L1 loop variable region of hexon gene of these isolates was amplified by PCR and sequenced. The nucleotide sequences (442 bp) and deduced amino acid sequences of the four isolates were compared with those of other isolates of FAV4. The nucleotide sequences of the four isolates had a 98% homology with other Indian isolates and a 96% homology with Belgian and Russian isolates. The amino acid sequences of the four Indian isolates had a more than 98% homology with other Indian isolates and a more than 92% homology with Belgian and Russian isolates. Hence, the variable of L1 loop region of hexon gene was found to be highly homologous in all the FAV4 isolates tested both at nucleotide and amino acid level.

Adenoviridae Infections↗

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla.

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE-/- mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 microm spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.

Animals↗

Prevalence of BSE in cattle found dead, euthanased or emergency slaughtered on farms in western France in 2000, 2001 and 2002.

The overall trend and the trend within birth cohorts of the prevalence of bovine spongiform encephalopathy (BSE) in cattle found dead, euthanased or emergency slaughtered on farms in the Bretagne, Basse Normandie and Pays de la Loire regions of France, during the periods from August 7 to December 22 in 2000, 2001 and 2002, were analysed by non-conditional logistic regression, adjusted for the region and for the type of animals. The overall prevalence of BSE during these three periods decreased from 2.71 per 1000 in 2000 to 1.41 per 1000 in 2001 and 0.42 per 1000 in 2002. The prevalence within birth cohorts started to decrease for the cohort born between July 1, 1995 and June 30, 1996 (cohort 95/96) and the trend was reinforced for cohort 96/97, suggesting that the exposure of animals to the BSE agent had started to decrease for animals born after July 1995, that is, one year before the ban on specified risk materials in meat and bone meal was implemented in France. However, considering that most of the animals would have been infected at between six and 18 months of age, the decrease may have been due, at least partly, to this control measure.

Age Factors↗

Structural brain abnormalities in multiple sclerosis patients with major depression.

OBJECTIVE: To assess the association between major depression and structural brain abnormalities in patients with multiple sclerosis (MS). METHODS: Two groups of patients with clinically definite MS were studied: 21 with Diagnostic and Statistical Manual of Mental Disorders (4th ed.)-defined major depression and 19 without. The groups did not differ on demographic, disease, or cognitive measures. All subjects underwent brain MRI. Tissue segmentation and regional brain masking were applied to the MRI data. RESULTS: Compared with the euthymic subjects, those with major depression had a greater T2-weighted lesion volume (p = 0.003) and more extensive T1-weighted lesion volume in the left medial inferior prefrontal cortex (p = 0.01) and less gray matter volume (p = 0.01) and more CSF volume in the left anterior temporal region (p = 0.005). A logistic regression analysis identified two independent predictors of depression: left medial inferior prefrontal cortex T2 lesion volume and left anterior temporal CSF volume. These variables accounted for 42% of the depression variance score. CONCLUSION: Whereas both lesion burden and atrophy are important in the pathogenesis of depression in MS, psychosocial influences should also be considered.

Adult↗

Strictureplasty.

BACKGROUND: Advances in the use of bowel-sparing surgery for Crohn's disease have led to the development of strictureplasty as an important technique to conserve small bowel length and reduce morbidity associated with malabsorption. METHODS: A literature review of long-term studies on strictureplasty was undertaken, and evidence of its safety and efficacy was evaluated. RESULTS: The safety and efficacy of strictureplasty is confirmed in retrospective studies carried out over a period of 5-10 years, particularly when employed in patients at risk of short bowel syndrome, but certain questions regarding bowel function and disease activity after surgery remain unanswered. There is also concern that diseased tissue is left in situ after strictureplasty; this tissue has the potential for malignant transformation in the long term. CONCLUSION: Strictureplasty has been used in surgery for Crohn's disease for the past 25 years. Studies have proven its efficacy in the treatment of carefully selected patients at risk of malabsorption owing to short bowel syndrome.

Crohn Disease↗

Survival, anatomic, and functional long-term results in choroidal and ciliary body melanoma after ruthenium brachytherapy (15 years' experience with beta-rays).

PURPOSE: To analyze survival, radiation-related complications, local recurrence, enucleation, and visual acuity after ruthenium-106 irradiation of malignant uveal melanoma. DESIGN: Retrospective study. METHODS: A total of 213 patients treated with ruthenium-106 brachytherapy between 1983 and 1995. End point rates were estimated by life tables, and prognostic factors by Cox proportional hazards regression. Main outcome measures were survival rate, radiation-related maculopathy, radiation-related vascular occlusion, local tumor recurrence, enucleation, and visual acuity (<20/100 at 3 years). RESULTS: At 5 and 10 years, survival was 82% (standard error [SE] 2.7%) and 72% (SE 3.4%), local recurrence 21.7% (SE 3.0%) and 24.3% (SE 3.2%), and enucleation 18.0% (SE 2.7%) and 19.2% (SE 2.8%), respectively. Sixty-one patients showed maculopathy (29%), 36 retinal vascular occlusion (17%), in 33 local recurrence (16%), and 38 enucleation (18%). Age and large tumor diameter were independently associated with survival (P <.0001 and P <.0075, respectively). Age below 40 and melanoma located posteriorly were significant risk factors for maculopathy (P <.0085 and P <.0004, respectively) and vascular occlusion (P <.0415 and P <.0114, respectively). Diameter and Bruch membrane rupture were significant predictors (P <.0032 and P <.0390, respectively) of local recurrence. Visual acuity <20/100 was observed in only 26 of 97 (27%) cases of anterior but 34 of 42 (81%) of posterior tumor (P <.001). CONCLUSION: Although percentage tumor recurrence was high, survival was comparable to series using other treatments. Radiation-related complication rates were acceptable, especially for anterior tumors. Ruthenium therapy can, therefore, be recommended for small and medium-sized tumors with anterior location.

Adult↗

Survival after proton-beam irradiation of uveal melanomas.

PURPOSE: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DESIGN: Interventional case series. METHODS: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P =.045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. CONCLUSION: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

Adult↗

[Benefits of a thickened infant formula with lactase activity in the management of benign digestive disorders in newborns].

This study aimed at evaluating the interest of a thickened infant formula with lactase activity by comparison with a standard infant formula in the management of benign digestive disorders in infants. Infants of both sex (N =109), ranging in age from 0 to 3 months, were included in a randomised double blind trial. Infants went to the paediatrician because of benign digestive disorders such as regurgitation, eructation or hiccup, colic, persistent crying and/or meteorism. Nine hundred and three infants were included and randomised in two parallel groups: they consumed daily either the thickened infant formula with lactase activity or a standard infant formula. There were no significant difference in the infants included in both groups. Both formula were well accepted and tolerated. Growth of the infants and compliance during the study were identical and good in the two groups. The efficiency of the formula tested was showed on digestive symptoms through: a decrease of the intensity of the digestive discomforts more important in the test than in the standard formula group; a decrease of the intensity of the gaz significantly more important in the test than in the standard formula group; significant decreases in frequency and intensity of the gaz in the test group while there were no significant diminution in the standard group; This study showed the good tolerance, acceptability and efficiency of a thickened infant formula with lactase activity on benign digestive disorders of young infants.

Dietary Supplements↗

Stewart-Treves syndrome--treatment and outcome in six patients from a single centre.

AIMS: Stewart-Treves syndrome is an angiosarcoma associated with long-standing lymphoedema, most commonly seen as a rare complication of breast cancer treatment, and is associated with a poor outcome. We present results from six patients supporting the use of early radical surgery to improve prognosis. METHODS: Six patients with Stewart-Treves syndrome were diagnosed and treated at our centre over an 11-year period. Five patients had forequarter amputation and the sixth had a through-hip amputation. RESULTS: Four of the six patients are alive and well following surgery (at 3, 16, 23, and 135 months after amputation); one patient died from metastatic disease at 15 months and the second died due to an unrelated malignancy. CONCLUSION: Early diagnosis and treatment by radical ablative surgery confers a reasonable prognosis with this rare but aggressive disease. A nihilistic approach is unjustified.

Aged↗