Flow simulations of rectal evacuation: towards a quantitative evaluation from video defaecography.

Mechanistic understanding of anorectal (patho)physiology is missing to improve the medical care of patients suffering from defaecation disorders. Our objective is to show that complex fluid dynamics modelling of video defaecography may open new perspectives in the diagnosis of defaecation disorders. Based on standard X-ray video defaecographies, we developed a bi-dimensional patient-specific simulation of the expulsion of soft materials, the faeces, by the rectum. The model quantified velocity, pressure and stress fields during the defaecation of a neostool with soft stool-like rheology for patients showing normal and pathological defaecatory function. In normal defaecation, the proximal-distal pressure gradient resulted from both the anorectal junction which formed a converging channel and the anal canal. The flow of the neostool through these anatomical parts was dominated by its shear-thinning viscous properties, rather than its yield stress. Consequently, the evacuation flow rate was significantly affected by variations in pressure applied by the rectum, and much less by the geometry of the anorectal junction. Lastly, we simulated impaired defaecations in the absence of obvious obstructive phenomena. Comparison with normal defaecation allowed us to discuss critical elements which should lead to effective medical management.

Towards an assessment of rectal function by coupling X-ray defecography and fluid mechanical modelling.

Despite the numerous available clinical investi-gation tests, the associated alteration of quality of life and the socio-economic cost, it remains difficult for physicians to identify the pathophysiological origins of defecation disorders and therefore to provide the appropriate clinical care. Based on standardized dynamic X-ray defecography, we developed a 2D patient-specific computational fluid dynamic model of rectal evacuation. X-ray defecography was carried out in a sitting position with a standardized paste whose yield stress matched that of soft human feces. The flow was simulated with lattice-Boltzmann methods for yield stress fluids and moving boundary conditions. The model was applied for a patient with a normal recto-anal function. We deduced from the flow field that the main flow resistance during the defecation was due to the extrusion of the paste through the anal canal. We calculated also from pressure and stress fields the spatio-temporal evolution of the wall normal stress. This latter highlighted a gradient from the proximal to the distal part of the rectum. We discussed how this new set of hydrodynamical and biome-chanical parameters could be interpreted to gain new insights on the physiology of defecation and to diagnose underlying evacuation disorders. Clinical relevance - If confirmed, our approach should allow clinicians to obtain other parameters from a classic clinical examination and thus better adapt the response of clinicians to the defecation disorders observed in patients.

Detection of enterovirus RNA in postoperative thyroid tissue specimens.

CONTEXT: Autoimmune thyroiditis is a very common disease. A genetic predisposition and environmental factors such as viruses are thought to contribute to the development of autoimmune thyroiditis. Enteroviruses, which are involved in other autoimmune diseases, are attractive candidates. OBJECTIVE: To investigate the presence of enteroviral genome sequences in postoperative thyroid tissues with lymphocytic infiltration, a common histological feature of thyroiditis. SUBJECTS AND METHODS: Postoperative thyroid specimens collected prospectively from 86 patients were blindly frozen at -80 degrees C. The presence of EV genome sequences in the samples was blindly investigated by real-time RT-PCR. Clinical data, histological findings and levels of anti-TPO antibodies were collected. RESULTS: EV-RNA detection was positive (up to 36 cycles) or weakly positive (37-39 cycles) in 22 out of 86 patients (25%). EV-RNA (positive or weakly positive signal) was detected in 5 out of 27 (18.5%) thyroid specimens with lymphocytic infiltration, and in 17 out of 59 (29%) thyroid specimens without lymphocytic infiltration (P = 0.4). No correlation was observed between EV-RNA detection in thyroid and the presence of anti-TPOAb. EV-RNA was detected in 3 out of 11 patients histologically diagnosed as thyroiditis (27.3%) and in 18 out of 74 patients (24.3%) with thyroid tumours (multinodular goitre, adenoma and carcinoma) (P = 0.5) and in one patient with a normal thyroid. CONCLUSION: EV-RNA can be detected in thyroid tissue from patients with various thyroid diseases, but there is no relationship between the presence of EV-RNA and thyroiditis. Further studies are needed to clarify the role of EV in thyroid diseases.

Technical and functional results after laparoscopic rectopexy to the promontory for complete rectal prolapse. Prospective study in 54 consecutive patients.

INTRODUCTION: Laparoscopic rectopexy for complete rectal prolapse offers short-term advantages compared with operations performed by laparotomy. The aim of this prospective study was to report technical and functional outcome after laparoscopic rectopexy to the promontory in consecutive patients operated on by a single surgeon. PATIENTS AND METHODS: From May 1996 to July 2004, 54 consecutive patients (47 women), median age 53 years (range: 16-84 years), underwent laparoscopic rectopexy to the promontory for complete rectal prolapse. Preoperative evaluation included physical examination, dynamic videoproctography and, in patients with constipation, colonic transit time (with radiopaque markers). Postoperative evaluation included the same examinations and a simple global quality-of-life questionnaire. RESULTS: Conversion to laparotomy was required for three patients during the learning curve. Median duration of operation was 157 minutes (range: 50-370). There was no mortality and morbidity was 5.5% (brachial plexus palsy in two patients and urinary tract infection in one). Median hospital stay was 3.5 days (range: 1-11). There were 4 recurrences (7.4%). Functional outcome at 12 months showed the presence of constipation in 20.3% of patients (persistence in eight and de novo in three) and the presence of outlet obstruction in 25.9% of patients (persistence in six and de novo in eight). Anal continence improved in 72.4% of the 29 patients who complained of this symptom. The global quality-of-life questionnaire showed a satisfactory result in 96% of patients. CONCLUSION: Laparoscopic rectopexy to the promontory is a safe and efficient procedure to treat complete rectal prolapse; morbidity is low. Functional outcome is at least equivalent to that obtained with open procedures in terms of continence, constipation and outlet obstruction.

[Larynx cancer in France: descriptive epidemiology and incidence estimation]. / Les cancers du larynx en France: éléments d'épidémiologie descriptive et estimation de l'incidence nationale.

The epidemiology of cancers is known in France through mortality data provided by Inserm and morbidity data obtained by French tumor registries. The purpose of this study was to compare the incidence of laryngeal cancers in 9 French departments and to give an estimate of this incidence for the whole of France, based on this data. Incidence and mortality data were collected over the period 1978-1997. The incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The estimated number of laryngeal cancers was 3,865 in males and 361 in females. There were pronounced contrasts in laryngeal cancer incidence between cancer registries. The incidence rate of laryngeal cancers were especially high in the Somme and Calvados department compared to those observed in Haut-Rhin and Tarn. The ratio incidence/mortality was 2.4 in Doubs and 1.3 in Somme. France is among the countries which have the highest rates of incidence and mortality for laryngeal cancer in Europe.

ZD1839 (Iressa) modifies the activity of key enzymes linked to fluoropyrimidine activity: rational basis for a new combination therapy with capecitabine.

PURPOSE: The efficacy of new oral fluoropyrimidines, including capecitabine, is improved in cells expressing high levels of thymidine phosphorylase (TP) and low levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase. We used a human head and neck cancer cell line (CAL33) to examine the influence of cell cycle modifications on TS, TP, and dihydropyrimidine dehydrogenase activity. EXPERIMENTAL DESIGN: Cells were exposed to the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa(2)) and 5'-deoxy-5-fluorouridine (5'-DFUR), alone and in combination, for up to 96 h, and modifications in cell cycle, enzyme activity, and gene expression were examined. RESULTS: ZD1839 (24- to 72-h exposure) markedly reduced proliferation and caused a rapid increase in G(0)-G(1) and a decrease in S phase; a 40-fold decrease in TS activity at 24 h and a 2.5-fold increase in TP activity at 48 h were observed. A significant link between TP activity and expression was observed (r(2) = 0.98; P = 0.0068). Additional investigations pointed out an increased cellular production of 5-fluorouracil anabolites from 5'-DFUR when cells were preincubated with ZD1839. Dose-effect curves of ZD1839 and 5'-DFUR, alone and in combination, were examined. Combination indices for ZD1839 + 5'-DFUR were 0.58 +/- 0.1 and 0.63 +/- 0.1 for 50% survival and 25% survival, respectively. Additional investigations pointed out an increased cellular production of 5-fluorouracil anabolites from 5'-DFUR when cells were preincubated with ZD1839. CONCLUSIONS: These data demonstrate a strong synergistic interaction between ZD1839 and 5'-DFUR when ZD1839 is applied before or concurrently with 5'-DFUR. Such a drug combination would have two advantages: (a) the theoretical advantage of tumor selectivity of epidermal growth factor receptor-targeted therapy; and (b) the practical advantage of a combination therapy that could be administered p.o.

Oxaliplatin-5-fluorouracil and ionizing radiation. Importance of the sequence and influence of p53 status.

OBJECTIVES AND METHODS: The association oxaliplatin (OXA)-5-fluorouracil/folinic acid (FUFA) is currently a standard first-line treatment for advanced colorectal cancer. The main objective of this experimental study was to examine the cytotoxic effects resulting from the addition of ionizing radiation (Rgamma) to the combination OXA-FUFA on 2 human colon cancer cell lines (SW403, p53 wild type and WiDr, p53 mutated). A clinically relevant drug sequence was used consisting in OXA during 2 h followed by FUFA over 24 h. The impact of the position of radiation (1 and 4 Gy) was tested: radiation 2 h before drug application, in the middle of the drug application or 24 h after the drug application. RESULTS: Both cell lines exhibited similar dose response curves to Rgamma alone, WiDr being more radio-sensitive than SW403 (IC50: 4.8 Gy and 7 Gy, respectively). The effects of Rgamma-drug combinations were assessed using a conventional isobolographic method and by computing a potentiation factor (F) defined as the ratio of IC50 drug combinations/IC50 drug combinations combined with Rgamma. The results from both calculation methods concurred: the combination of OXA-FUFA with Rgamma led to additive-antagonistic effects for the p53 mutated cell line (WiDr), whatever the sequence. In contrast, for the p53 wild type cell line (SW403), additive-synergistic effects were observed with, in this case, an optimal position for Rgamma occurring when applied before or at mid-drug application. CONCLUSIONS: These results could be taken into consideration for an optimal design of clinical protocols associating Rgamma and OXA-FUFA.

The concept of persistence as applied to metals for aquatic hazard identification.

The criteria persistence (P), bioaccumulation (B), and toxicity (T) are applied by domestic and international regulators and modelers to the hazard identification of chemical substances, including metals and metalloids, that may present harm to the environment. In this paper, we critically examine the literature to determine the weight of evidence for the application of water column partition half-times as a surrogate for the persistence criterion in the aquatic hazard identification of metals and metal compounds. Dissolved metals such as Fe, Mn, Cu, Pb, Co, Cs, Hg, and Zn, as well as the metalloids As and Se, tend to partition from the water column by adsorption onto sinking particulates, with reported and calculated partition half-times in the range 4 to 30 d, with outliers of 0.07 and 280 d. Within freshwater lakes, values of t1/2 for the transition metals Cr, Mn, Fe, Co, and Cu averaged about 10 d, while those for the nontransition metals Sr, Zn, Cs, and Hg and the metalloids As and Se varied up to 55 d. These data are consistent with the well-established complexing properties of the transition metals, which are significantly greater compared to the nontransition metals and the metalloids. While the considerable variations in the literature at present preclude the use of metal partition half-times in aquatic hazard identification, the surrogate for the persistence criterion could be the partition half-time of the bioavailable fraction of the total dissolved metal concentration as determined in a laboratory protocol under standardized conditions.