Search

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals >= 500 ms. No correlation between Escit-PL and QTc-length was found (r = 0.08; p = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted beta = 0.26, SE = 9.1; p = 0.01) was an independent predictor of QTc-length (R (2) = 0.096, F = 4.68, df = 2,88; p = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01-12.52]; p < 0.05) and medication load (OR 1.32 [95% CI 1.06-1.64]; p < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test chi (2) = 9.5, df = 2; p < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.

There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n = 53); melphalan (n = 83); or a combination of thiotepa, fludarabine, and busulfan (n = 50). A parametric model, with detailed Tac-Sir consecutive blood levels, describing time to AKI was developed using the NONMEM software version 7.4. Overall, 81 of 186 (44%) RIC allo-HSCT recipients developed AKI with a cumulative incidence of 42% at a median follow-up of 25 months. Time to AKI was best described using a piecewise function. AKI-predicting factors were melphalan-based conditioning regimen (HR, 1.96; P < .01), unrelated donor (HR, 1.79; P = .04), and tacrolimus concentration: The risk of AKI increased 2.3% per each 1-ng/mL increase in tacrolimus whole blood concentration (P < .01). In multivariate analysis, AKI grades 2 and 3 according to KDIGO staging were independent risk factors for 2-year nonrelapse mortality (HR, 2.8; P = .05; and HR, 6.6; P < .0001, respectively). According to the KDIGO score, overall survival decreased with the increase in severity of AKI: 78% for patients without AKI versus 68%, 50%, and 30% for grades 1, 2, and 3, respectively (P < .0001). In conclusion, AKI is frequent after Tac-Sir-based RIC allo-HSCT and has a negative impact on outcome. This study presents the first predictive model describing time to AKI as a function of tacrolimus drug concentration. (C) 2017 American Society for Blood and Marrow Transplantation.

The puborectoplasty in fecal incontinence (FI) has been described through retropubic approach. Here, we describe a puborectal sling placement through transobturator approach with a device used for vaginal vault prolapse and report long-term outcome at 5 years. Six women with FI for whom usual treatments (including sacral nerve stimulation) have failed were enrolled in a pilot study. Cleveland Clinic Incontinence Score (CCIS) and FI quality of life (FIQL) were used to evaluate results. The median CCIS was significantly improved at 12 months (18.5 [15–20] vs 7.5 [4–20] in postoperative assessment; p = 0.037). The median FIQL was improved at 12 months (6.05 [5.6–7] vs 10.2 [5.6–12.5]; p = 0.0542). No adverse event was recorded except the distension of the device in one patient. Finally, at 5 years, 3 patients were improved, 1 had recurrence of FI symptoms (at 24 months) and 2 had no change. This technique is a minimally invasive surgical treatment and constitutes a new therapeutic option for FI in case of failure of conventional treatment.

Resume Objectifs Evaluer l’efficacite et les resultats fonctionnels (activite sexuelle) du lambeau d’avancement vaginal dans le traitement des fistules recto-vaginales de la maladie de Crohn. Patientes et methodes De mai 2004 a mars 2008, nous avons propose un lambeau d’avancement vaginal aux patientes qui presentaient une fistule recto-vaginale de la maladie de Crohn et pour qui le lambeau rectal etait techniquement impossible. Le suivi comprenait un examen clinique a 1 mois puis tous les 3 mois pendant 1 an, le PDAI pour l’evaluation de l’activite sexuelle. Chaque annee et en avril 2009, l’equipe de soins infirmiers au cours d’un entretien telephonique remplissait un questionnaire standardise. Resultats Nous avons traite 5 patientes. A 6 mois, 4 des 5 patientes etaient gueries. A 7 mois, une patiente presentait une nouvelle poussee de la maladie de Crohn avec reouverture de la fistule. Les 3 autres patientes etaient gueries avec un suivi median de 30,66 mois (15 a 59). Une patiente presentait une dyspareunie pendant 3 mois. Les bons resultats obtenus par cette technique sont tres probablement favorises par les anti-TNFα. Discussion et conclusion Il s’agit d’une technique efficace qui ne s’accompagne pas de dyspareunie prolongee, la stomie n’est pas systematique.

Summary Objectives In France, seton drainage followed by fistulotomy is currently the standard treatment for high cryptoglandular fistula-in-ano. Biological or synthetic glues, such as Glubran ® 2, have been recently proposed for sealing the fistula tract. The purpose of this study is to determine the healing rate with glubran 2 and to assess the functional outcome after cure of fistula-in-ano. Patients and methods From July 2006 to July 2008, 34 patients (20 males; median age 48.5 years, range 22–55 years) with high cryptoglandular anal fistulas were treated with glubran 2. Patients were seen for physical examination at 1, 3 and 6 months, then interviewed by telephone at 1 and 2 years, and in September 2009. The Fecal incontinence severity index (FISI) score was used to assess continence. Results The healing rate at 1 month was 67.6% (23 patients); the fistula failed to heal in 11 patients. All 23 patients with a healed fistula remained recurrence-free, with no continence disorders noted, during the median 34-month follow-up period (range 21–43 months). One patient was lost to follow-up after 6 months. Conclusion Glubran 2 provides an effective treatment for high fistula-in-ano, with no change in continence. In future, a randomized comparison of this agent with fibrin glues should be useful.

Background/Aims: Mutations in the PRSS1 and the SPINK1 genes have variably been associated with alcohol-related, idiopathic and hereditary chronic pancreatitis (CP). The aim of this study was to determine for the first time the significance of PRSS1, SPINK1 mutations and genetic variants of AAT in a group of Spanish patients with CP. Methods: 104 consecutive patients with CP were included, as well as 84 healthy control subjects. The R122H and N29I mutations in the PRSS1 gene, the N34S mutation in the SPINK1 gene and PiS and PiZ mutations in the AAT gene were analyzed by RFLP-PCR methods. Results: No R122H mutation was found in the PRSS1 gene, and N29I mutation was detected in 7.7% of CP patients. A N29I mutation was observed in 3.9% of patients with alcohol-related pancreatitis (ACP). A total of 5.8% of CP patients were identified with the N34S mutation. Genotype MS, SS and MZ were detected in 18.3, 3.8 and 1.3% of CP patients, respectively. Conclusion: The percentage of N29I mutations in ACP patients was higher than that reported in other studies, while the percentage of N34S and AAT mutations in ACP and idiopathic CP patients was similar. Copyright (C) 2009 S. Karger AG, Basel and IAP

Background: Reference intervals for serum creatinine remain relevant despite the current emphasis on the use of the estimated glomerular filtration rate for assessing renal function. Many studies on creatinine reference values have been published in the last 20 years. Using criteria derived from published IFCC documents, we sought to identify universally applicable reference intervals for creatinine via a systematic review of the literature.Methods: Studies were selected for inclusion in the systematic review only if the following criteria were met: (a) reference individuals were selected using an “a priori” selection scheme, (b) preanalytical conditions were adequately described; (c) traceability of the produced results to the isotope dilution–mass spectrometry (IDMS) reference method was demonstrated experimentally, and (d) the collected data received adequate statistical treatment.Results: Of 37 reports dealing specifically with serum creatinine reference values, only 1 report with pediatric data and 5 reports with adult data met these criteria. The primary reason for exclusion of most papers was an inadequate demonstration of measurement traceability. Based on the data of the selected studies, we have collated recommended reference intervals for white adults and children.Conclusion: Laboratories using methods producing traceable results to IDMS can apply the selected reference intervals for serum creatinine in evaluating white individuals.

Background Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. Patients and methods Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. Results Mean BU exposure (AUCss) (+/-DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade > or = II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. Conclusions The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD.

Neural networks are specialized artificial intelligence techniques that have shown high efficiency in dealing with complex problems. Paradigms such as backpropagation have been successfully applied in a number of biomedical applications, but not in attempts to identify women at risk of postmenopausal osteoporotic complications. In this paper, several neural networks were trained using different combinations of biochemical variables as inputs. Bone densitometric measurements in Ward's triangle and in the spinal column were used as separate classification criteria (outputs) between slow and fast bone mass losers. The most parsimonious model with the best performance included plasma concentrations of estrone, estradiol, osteocalcin, parathyrin and urine concentrations of calcium and hydroxyproline (expressed as ratio to creatinine excretion) as input neurons; ten neurons in a single hidden layer; and one neuron in the output layer. Diagnostic efficiency was 76 % in Ward's triangle and 74 % in the spinal column; sensitivity was 70 and 81 %, and specificity was 77 and 65 %, respectively. Linear discriminant analysis showed a diagnostic efficiency of 66 % in Ward's triangle and 64 % in the spinal column, sensitivity was 55 and 86 %, and specificity was 75 and 13 %, respectively. We conclude that performance of the stepwise discriminant analysis was not superior to the neural networks.

SummaryIntroduction Patients with persistent high levels of serum vitamin B12 were often referred to Hematology departments. In this study, characteristic of patients with serum vitamin B12 levels higher than 2500 pmol/L (high B12) were studied. Methods Prevalence of high B12 was evaluated during a 10-month period. Samples with high B12 were incubated with polyethylene glycol (PEG) and a new measurement of vitamin B12 was carried out using the supernatant. As a pilot study, 26 frozen samples with high B12 were evaluated for changes in vitamin B12 after PEG. Moreover, a prospective study was carried out during three consecutive months. Size exclusion chromatography was employed to demonstrate the presence of immune complexes (ICs) with plasma vitamin B12-binding proteins in some serum samples with high B12. Results Prevalence of high B12 was 1.3%. Results from 26 frozen samples and from a prospective study (28 cases) showed that undergoing vitamin B12 treatment was the main cause of high B12. However, ICs were detected in 10 frozen samples and in seven cases (25%) of the prospective study, respectively. Serum vitamin B12 decreased to normal values after precipitation with PEG, and size exclusion chromatography confirmed ICs. An association with autoimmune or hematological disorders was observed. Conclusions In patients with repeatedly high B12 levels, ICs were detected in approximately 25% of samples. Precipitation with PEG is an easy method to confirm the presence of ICs and to evaluate serum vitamin B12 levels in these patients.

This study was conducted to assess the predictive value of different variables including the response to dexamethasone suppression test (DST), in 105 patients with resistant depression after the addition of lithium (600 to 800 mg/day) for 4 weeks to antidepressant medication. Clinical remission was observed in 57 patients and no improvement in 48. A dramatic and rapid relief of depression occurred in 12 patients. Variables with significant or marginally significant differences between responders and non-responders were included in a stepwise logistic regression model. Weight loss (P = 0.0013) and depressive psychomotor activity (P = 0.045) in the Newcastle diagnostic index (NDI) scale, and overall score of the Hamilton Rating Scale for Depression (HRSD) before adding the lithium (P = 0.0039) were significantly associated with clinical remission. The difference in post-DST cortisol plasma levels between both groups was marginally significant. The logistic equation resulted in a sensitivity of 78% and a specificity of 65% and total correct classification of the lithium-added response of 72%. The clinical profile of patients who improve with the addition of lithium may include significant weight loss, psychomotor retardation and possibly, poor control of cortisol secretion. Partial remission before adding lithium as well as endogenomorphic traits according to NDI may also be considered additional criteria for response.

Plasma holotranscobalamin (holoTC) transports active cobalamin. Decreased levels of holoTC have been considered to be the earliest marker of cobalamin (Cbl) deficiency. In this work, holoTC was evaluated in low or borderline serum Cbl (LB12) and a concordance analysis was carried out with methylmalonic acid (MMA) and homocysteine (Hcy). Levels of Cbl, holoTC, MMA, and Hcy were investigated in a reference group in 106 patients with LB12 (≤200 pmol/l) and in 27 with folate deficiency (FOL). HoloTC levels were evaluated by an automated immunoassay (Active B12, Abbott Lab, Abbott Park, IL, USA). Lower levels of holoTC were observed in both LB12 and FOL groups (reference group vs LB12; p < 0.0001. Reference group vs FOL; p = 0.002). HoloTC levels were lower in LB12 than in FOL (p = 0.001). In LB12, concordance between Hcy and MMA was 82.1 % (chi-square test, p < 0.001; Kappa Index, 0.64, p < 0.0001). Concordance between Hcy and holoTC was 62 % (chi-square test, p = 0.006; Kappa index, 0.245, p = 0.006). Concordance between holoTC and MMA was 55.6 % (p = 0.233). Some cases with LB12 and elevated MMA did not show decreased holoTC. By contrast, MMA and Hcy were not increased in some patients with low holoTC and LB12. In conclusion, levels of holoTC were decreased in LB12 and FOL. In LB12 patients, holoTC concordance with MMA was poor. MMA/Hcy levels were not increased in a significant number of subjects with LB12 and low holoTC. This profile was found in iron deficiency. The significance of these changes remains to be clarified.

Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The objective of this work was to investigate the degree of overlap between iron deficiency anemia (IDA) and cobalamin deficiency and to develop a predictive model for differentiating IDA from combined deficiency. A prospective case and control study was carried out to investigate vitamin B-12 and folate status in iron deficiency anemia. A total of 658 patients were recruited, 41 of whom (6.2 %) were excluded. The remaining 617 subjects consisted of 130 controls and 487 with IDA. Low vitamin B-12 (LB12) was considered when serum vitamin B-12 was a parts per thousand currency sign200 pmol/L. High serum homocysteine (Hcy) was defined by Hcy > 17 mu M/L. A multivariate analysis (including a logistic regression) was performed to develop a diagnostic model. Low vitamin B-12 levels were found in 17.8 % of IDA subjects. Ten out of 11 subjects (91 %) with IDA and serum vitamin B-12 (B12) a parts per thousand currency sign100 pmol/L showed vitamin B-12 deficiency. Moreover, vitamin B-12 deficiency was demonstrated in 48 % of cases with IDA and B12 between 101 and 150 pmol/L and in 40 % with IDA and B12 between 151 and 200 pmol/, respectively. As a result of multivariate logistic analysis, neutrophil counts and age predicted subjects with vitamin B-12 a parts per thousand currency sign200 and Hcy > 17 mu mol/L, . Using the age of 60 as a cutoff, sensitivity was 91 % (39 out of the 43 patients with vitamin B-12 deficiency and IDA were identified). In summary, low vitamin B-12 was found in 18 % of patients with IDA. Vitamin B-12 deficiency was demonstrated in many patients with LB12 and IDA. Age over 60 years was used to separate patients with combined deficiency (sensitivity 91 %). Therefore, for a diagnostic purpose, serum vitamin B-12 should be evaluated in IDA patients over 60 years. This diagnostic model needs to be validated in a different population.

International audience; Aim: The study aimed to assess, for the first time, the effectiveness of interferential therapy (IFT) in the treat-ment of slow transit constipation in adults and its impact on the quality of life.Method: All consecutive patients with slow transit constipation diagnosed by symptomology and a colonic transit time (CTT) of > 100 h measured with radiopaque markers were included in this prospective study. IFT was performed for 1 h/day over 3 months. Clinical improvement was based on the stool diary and the Knowles–Eccersley–Scott Symptom and Cleveland Clinic Constipation Scores. Quality of life was assessed with the Gastrointestinal Quality of Life Index questionnaire.Results: Eleven patients with a median age of 51 years were included. At the end of the follow-up period, seven (63.6%) had significantly improved after IFT with a median of 0.66 stools per week [interquartile range (IQR) 0.33–0.66] before treatment and 1.66 (IQR1.33–1.66) after (P = 0.007). The Knowles–Eccersley– Scott Symptom score changed from 30 (IQR 27–33) before treatment to 19 (IQR 17–26) after treatment (P = 0.005) and the Cleveland Clinic Constipation Score from 26 (IQR 25–28) to 17 (IQR 13–24; P = 0.005). The CTT improved from 103 h (IQR 101–113) to 98 h (IQR 94–107; P = 0.02). The Gastrointestinal Quality of Life Index score improved from 60 (IQR 57–63) to 95 (IQR 68–100; P = 0.005).Conclusion: IFT is a new non-invasive treatment for slow transit constipation. Further studies to confirm these results with longer follow-up are necessary.

This study aimed at assessing the relationship between thrombosis, hyperhomocysteinemia and vitamin B12 deficiency using a case–control study carried out in 326 patients with thrombosis (case group) and 351 patients from the same hospital (control group). Apart from the classic risk factors, a number of hematological variables were evaluated, including serum vitamin B12 (B12), red cell folate (RCF), and serum homocysteine (Hcy). An evaluation of serum methylmalonic acid (MMA) and a clinical study were carried out to investigate B12 pathology. Results of univariate analysis demonstrated decreased B12 levels in thrombosis (Student’s t test, p < 0.0001). Vitamin B12 below 200 pmol/l (LB200) or below 150 pmol/l (LB150), and red cell folate below 600 nmol/l were found in 17.2, 8.6, and 2.2% of cases with thromboembolism, respectively. An increase in Hcy was detected in 86 cases with thrombosis (26.3%). An abnormality in vitamin B12 and/or renal function was found in 80% of cases with hyperHcy and thrombosis. The MMA increase demonstrated that vitamin B12 deficiency was present in these patients with low levels of vitamin B12 in serum, and the MMA levels were in concordance with Hcy levels. The clinical study revealed B12 malabsorption in most cases with LB200. Multivariate analysis showed that serum vitamin B12 (RR 0.998, CI 0.997–0.999) was moderately related to thromboembolism. The results indicated that vitamin B12 deficiency was common among patients with hyperhomocysteinemia and thrombosis. Moreover, HyperHcy was caused by vitamin B12 deficiency and/or chronic renal failure in most patients with thrombosis. As the main cause of vitamin B12 deficiency was vitamin malabsorption, parenteral vitamin B12 with or without folic acid should be administered for the treatment of this condition. However, it remains to be demonstrated whether this treatment approach prevents recurrent thromboses in patients with vitamin B12 deficiency and thrombosis, as suggested by some case reports.

Background: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. Methods: AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18–85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. Results: AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 μkat/L), allowing a single RI of 11–34 U/L (0.18–0.57 μkat/L) to be defined. Interregional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8–41 U/L (0.13–0.68 μkat/L) for females and 9–59 U/L (0.15–0.99 μkat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6–40 U/L (0.11–0.66 μkat/L) for females and 12–68 U/L (0.20– 1.13 μkat/L) for males, respectively. Conclusions: For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is applicable worldwide appears unlikely due to differences among populations. Clin Chem Lab Med 2010;48:1593–601.

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article. Clin Chem Lab Med 2010;48:999–1008.

Objective: The activity of cytochrome P-450 enzyme 2D6 (CYP2D6) could be related to heroin-dependent patient satisfaction with methadone maintenance treatment. We sought to compare satisfaction with the usual methadone treatment in patients who are ultrarapid, extensive or poor metabolizers, according to CYP2D6 genotyping. Methods: Two hundred and five heroin-dependent patients filled out the Verona Service Satisfaction Scale for methadone maintenance treatment (VSSS-MT), before CYP2D6 genotyping. Results: VSSS-MT overall scores were comparable in the poor metabolizer (N = 9) and extensive metabolizer (N = 185) groups, although they were higher in poor metabolizers and extensive metabolizers taken together than in the ultrarapid metabolizers (N = 11) (p < 0.003). Likewise, ultrarapid metabolizers scored higher than the rest of the sample on the VSSS-MT Basic Interventions subscale (p < 001). Regarding this subscale, no poor metabolizers felt dissatisfied, and ultrarapid metabolizer males (N = 7) reported lower satisfaction than ultrarapid metabolizer females (N =4 ) (p < 0.022). Ultrarapid metabolizer genotype accounted for 4.2% of the variance on the VSSS-MT total scores, and 5.0% on the Basic Intervention scores. Conclusion: Heroin-dependent patients who are CYP2D6 ultrarapid metabolizers according to genotyping present deficient satisfaction with methadone maintenance treatment. © 2007 Elsevier Ireland Ltd. All rights reserved.

We estimated reference change value and steady state disease biological variation of glycohemoglobin (HbA1c) from serial measurements in 47 clinically stable type 2 diabetes patients whose home-measured capillary glucose was stable throughout the study. Whole blood HbA1c assays were performed by turbidimetric inhibition immunoassay. The analytical imprecision (coefficient of variation) was 7.1% and 5.0% for control materials with HbA1c of 5.1% and 10.7%, respectively (n=152). The sampling interval was 6 months. Patients were classified into three groups (good, acceptable and poor control) according to the American Diabetes Association (ADA) clinical practice recommendations of 1999 based on HbA1c reference interval. Steady state disease biological variation for each control group was 7.9%, 5.4% and 3.9%. HbA1c absolute reference change value was 1.42, 1.50 and 1.37%, or as relative reference change value, 29.1%, 24.4% and 17.8%, respectively. The analytical goal, defined as one-half of the biological variation, was lower than 3.9% for well-controlled patients.

Diffuse esophageal leiomyomatosis is a rare disorder which may be found in association with leiomyomas in other locations or with other disorders. We report two cases in men, one with associated tracheobronchial involvement, which illustrate the value of imaging in differentiating this entity from other causes of dysphagia and in establishing a diagnosis.

Summary: Dynamic interpretation of results is an alternative approach to the conventional cut-off procedure. Reference change limit is a valuable reference point to interpret dynamically tumour marker values when only very few serial results can be obtained from a patient after treatment. In this paper, a reference change limit of 2.0 μ§/1 was estimated for carcinoembryonic antigen in patients with complete remission of colorectal cancer. This figure means that a difference greater than 2.0 μg/l has at least a chance of being statistically significant (at 0.05 probability). As complementary information to the reference change limits, with more than four successive results, a simple time series model can be used to obtain predictive limits for the next observation.

Introduction La prise en charge des fistules rectovaginales de la maladie de Crohn (FRV MC) implique une approche multidisciplinaire gastro-enterologique, colo-proctologique et gynecologique. Lorsque l’orifice rectal est bas, de diametre peu important, le traitement chirurgical de reference est le lambeau d’avancement rectal [(flap rectal (FR)], realise sur un rectum sans lesion Crohnienne active, apres un drainage sur seton lâche [1, 2]. Peut-on proposer un flap vaginal (FV) comme traitement alternatif au FR lorsque celui-ci est techniquement impossible ? Patients et Methodes De mai 2004 a mars 2008 nous avons propose aux patientes qui presentaient une FRV MC et chez lesquelles un FR n’etait pas possible, un flap vaginal (FV) en precisant que le traitement n’etait pas valide, l’alternative etant le drainage prolonge sur seton. Apres traitement medicamenteux de la poussee, verification de l’absence de lesion active par coloscopie, la technique employee etait le « miroir » du FR : confection d’un lambeau qui debutait au niveau de la fourchette et qui s’etendait sur 2,5 a 3 cm de hauteur au dessus de l’orifice, fermeture de l’orifice vaginal, et lorsque cela etait possible, une petite myorraphie recouvrait l’orifice prealablement ferme, la reparation etait recouverte par le FV. Aucune diversion n’etait realisee. Une antibiotherapie orale, avec 1 g de ciprofloxacine et 1 g de metronidazole, etait prescrite en postoperatoire pendant sept jours. Les bains etaient contre-indiques pendant 15 jours. Resultats Nous avons propose ce traitement a 6 patientes, 5 l’ont accepte. L’âge moyen etait de 51,6 ans. Les patientes etaient revues a 8 semaines, puis tous les 3 mois. A 8 semaines 4 des 5 patientes etaient cicatrisees, la patiente qui n’avait pas cicatrise avait subi une colectomie totale avec anastomose ieorectale. A 6 mois, une patiente a presente une poussee de la MC avec reouverture de la fistule. Les 3 autres patientes etaient toujours cicatrisees sur un suivi median de 23,8 mois (11 a 52). Discussion Lorsque pour des raisons techniques le lambeau ne peut etre realise (stenose anale et/ou sclerose de la paroi rectale), un drainage sur seton ou l’abstention therapeutique sont les solutions le plus souvent choisies. Les gros orifices, les fistules hautes, sont traites par une interposition de tissu (graciloplastie, Martius…). Conclusion Le FV est une technique simple, peu agressive, ne necessitant pas de derivation, probablement efficace, qui merite d’etre proposee lorsque le FR n’est pas techniquement possible.

Introduction Plusieurs options chirurgicales peuvent etre proposees chez les patients presentant une incontinence anale (IA) et une rupture sphincterienne. La sphincteroplastie est la plus largement pratiquee, mais sa morbidite est significative et a moyen terme son efficacite est reduite. Conaghan et Farouk ont observe de bons resultats de la neuromodulation sacree (NMS) pour des patientes presentant une rupture du sphincter externe [1]. Recemment nous avons rapporte l’utilisation de la STP par TENS dans le traitement de l’incontinence anale idiopathique [2]. Cette etude a ete concue pour determiner si les indications STP par TENS pouvaient etre etendues aux patients presentant une incontinence anale et une lesion sphincterienne. Patients et Methodes De juillet 2004 a septembre 2007 nous avons propose ce traitement aux patients qui consultaient pour IA en rapport avec une rupture sphincterienne et qui relevait d’une reparation sphincterienne. Nous avons informe les patients qu’il s’agissait d’un traitement en evaluation et que a tout moment, ils pouvaient opter pour la solution chirurgicale prealablement prevue. L’evaluation pre-therapeutique incluait un examen medical detaille un examen des cahiers de selles, une echographie endo-anale, une manometrie ano-rectale. Le score de Wexner et la version francaise de la qualite de vie de l’incontinence fecale ont ete employes pour mesurer la severite de l’incontinence avant, et apres traitement. En fin de traitement les patients representaient leur satisfaction vis-a-vis de ce traitement sur une echelle analogique de 10 cm (EVA). Une unite TENS (Schwa-medico) delivrait un courant de 200-μs, 10-Hz tous les jours pendant 4 semaines au domicile des patients. Les patients etaient revus a 1 mois, 3 mois 6 mois puis tous les ans. Resultats Nous avons ainsi traite par STP 21 patients (19 femmes) d’âge median de 57,4 ans (48 - 71). Tous les patients avaient un defect du sphincter externe mesure entre 40° et 110°. 7 avaient un defect associe du sphincter interne mesure entre 140° et 180°. L’etiologie de l’incontinence etait 16 fois obstetricale et 3 fois traumatique (fistule), 2 fois traumatique et obstetricale (hemorroidectomie, viol). 12 des 21 patients traitees par STP ont rapporte une diminution des episodes d’incontinence et une amelioration de qualite de la vie, l’EVA median etait de 6,5 (4 - 9). Les 12 patients qui ont repondu a la STP (amelioration du Wexner d’au moins 30 % et ou diminution du nombre d’accident d’IA de 50 %) ont prefere poursuivre le traitement (quotidiennement pendant 3 mois puis 5 jours par semaines) que de subir une reparation sphincterienne et ce sur un recul median de 21 mois (15 - 34). Conclusion Notre etude suggere que dans cette indication, la STP par TENS doit probablement etre essayee avant la NMS. Remerciements, financements, autres Remerciements au Dr Laurent Abramowitz (GREP).

Introduction Le traitement chirurgical des fistules anales hautes doit tenir compte de deux logiques opposees : respecter les sphincters, garant d’une guerison sans sequelle sur la continence, eradiquer le trajet fistuleux, garant d’une guerison sans recidive. Actuellement, la technique du drainage par seton puis la section progressive des sphincters est la methode la plus employee en France, elle a comme avantages d’etre simple, de ne presenter qu’un faible taux de recidives, mais a comme inconvenient d’avoir un taux de morbidite non negligeable sur la continence. Depuis la mise sur le marche de colles et de bouchons, les techniques « d’epargne sphincterienne » connaissent un regain d’interet. Nous avons voulu evaluer le cyanoacrylate (colle chimique) [1] dans le traitement des fistules hautes tant sur le taux de cicatrisation que sur les resultats fonctionnels. Patients et Methodes De juillet 2006 a juillet 2008 nous avons propose ce traitement aux patients qui presentaient une fistule anale cryptoglandulaire haute. Apres un drainage sur seton lâche, le trajet fistuleux etait curete et lave. La colle etait injectee lentement par l’intermediaire d’un catheter prealablement place dans le trajet. Lorsqu’une bulle de colle apparaissait a l’orifice interne, le catheter etait lentement retire, la colle etait injectee jusqu’a la sortie du catheter. Une antibiotherapie orale, avec 1 g de ciprofloxacine et 1 g de metronidazole, etait prescrite en postoperatoire pendant sept jours. Les bains etaient contre-indiques pendant 15 jours. Les patients ont ete revus a un, trois et six mois, a 1 et 2 ans ils etaient contactes par telephone, on recherchait une recidive, une incontinence anale, des suintements. Resultats 34 patients consecutifs (20 hommes) ont ainsi ete traites. A un mois 23 (67,4 %) patients etaient gueris. Il n’a pas ete observe de recidive sur un suivi median de 15,5 mois (3 a 27 mois), 11 patients ont presente un echec. Un patient a ete reencolle 2 fois sans succes. Six fois, nous avons observe des complications : trois fois, un cone de colle trop important etait responsable de douleurs au niveau de l’orifice secondaire, l’excision de l’excedent de colle a permis la regression immediate des symptomes ; deux fois, des douleurs anales ont cedees a des antalgiques ; enfin une fois, une ulceration creusante au niveau de l’orifice interne etait responsable de douleurs imposant la prescription de morphiniques, la cicatrisation a ete longue : dix semaines. Aucun des 23 patients cicatrises n’a presente des troubles de la continence. Conclusion Le traitement par cyanoacrylate est peu onereux, simple, permet une reprise rapide des activites, le taux de cicatrisation est satisfaisant sans alteration de la continence. Des complications mineures ont ete observees au debut de notre experience et peuvent etre evitees. Une complication connue et imputable au produit, rare mais severe doit nous inciter a evaluer avec le patient les avantages attendus par rapport au risque.

Phenylacetic acid (PAA), a metabolite of phenylethylamine, has been found in the urine of depressed patients at lower levels than in control subjects. It has been suggested that the determination of PAA in urine could be used as a biological marker of the depressive condition. In this study the levels of PAA in urine were investigated by gas-liquid chromatography in 39 patients diagnosed as having major depression according to DSM-III criteria, and in 32 healthy subjects. The values found in the patients were markedly lower than in controls. No relationship was found between the decrease of PAA excretion and weight loss. Using a discriminant equation, a value of 69% was obtained for both sensitivity and specificity. The results suggest that the determination of urine PAA could be a biological parameter comparable to the dexamethasone suppression test.

We evaluated the analytical and clinical performance of six commercial immunoradiometric assay kits for thyrotropin (TSH) in serum in 218 subjects, with and without thyroid dysfunction. Detection limits of the six kits were lower (from 0.07 to 0.25 milli-int. unit/L) than that of conventional TSH RIA (0.7 milli-int. unit/L). Precision was adequate over a wide range of concentrations, although interassay CVs at very low concentrations were good for only two kits (7.3% and 13.1%). Results by all the kits correlated to about the same degree with the TSH RIA (r = 0.92 to 0.98). All showed a positive correlation between both the basal and post-thyroliberin (TRH)-stimulation values for TSH (r = 0.78 to 0.88), and all showed similar euthyroid reference ranges for basal concentrations of TSH. With four of the six kits we could clearly distinguish most of the hyperthyroid patients from healthy euthyroids; however, basal and post-TRH TSH values were not sufficient to discriminate among groups of patients with different grades of thyroid hyperfunction.