Use of immediate release melatonin in psychiatry: BMI impacts the daily-dose.

OBJECTIVE: There is a growing interest in psychiatry regarding melatonin use both for its soporific and chronobiotic effects. This study aimed to evaluate factors impacting the daily-dose. METHODS: In a university department of psychiatry in Paris (France), we conducted a posteriori naturalistic observational study from April 03, 2017 to January 31, 2018. We assessed links between sociodemographic and clinical characteristics and daily dose of melatonin (the daily-dose of melatonin initiation and the daily-dose at Hospital discharge). A survey of drug interactions was performed regarding metabolic inducers and inhibitors of the cytochrome P450 1A2. RESULTS: Forty patients were included and treated with immediate-release melatonin. For patients with no history of melatonin use, the initiation dose of was 2 or 4mg, with no effects of age, weight, BMI, melatonin indication, cause of hospitalization. We found that higher discharge dose was associated with higher BMI (P=0.036) and more reevaluations of melatonin dose (P=0.00019). All patients with a moderate inducer (n=3, here lansoprazole) were significantly more associated with the discontinuation melatonin group (P=0.002). CONCLUSION: The BMI and the number of reevaluations impact the daily dose of melatonin. Two mechanisms may explain that BMI may need higher doses: (i) melatonin diffuses into the fat mass, (ii) the variant 24E on melatonin receptor MT2, more frequent in obese patients, leads to a decrease of the receptor signal.

Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients.

OBJECTIVES: HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. METHODS: In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). RESULTS: Volumetric trabecular bone density was 17% lower in the tibia (P < 10(-4) ) and 16% lower in the radius (P < 10(-3) ) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10(-4) for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10(-3) and 10(-2) , respectively). Cortical thickness was not different between the two groups. CONCLUSIONS: The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients.

Characterization of Restenosis following Carotid Endarterectomy Using Contrast-Enhanced Vessel Wall MR Imaging.

BACKGROUND AND PURPOSE: Restenosis is an important determinant of the long-term efficacy of carotid endarterectomy. Our aim was to assess the role of high-resolution vessel wall MR imaging for characterizing restenosis after carotid endarterectomy. MATERIALS AND METHODS: Patients who underwent vessel wall MR imaging after carotid endarterectomy were included in this study. Restenotic lesions were classified as myointimal hyperplasia or recurrent atherosclerotic plaques based on MR imaging features of lesion compositions. Imaging characteristics of myointimal hyperplasia were compared with those of normal post-carotid endarterectomy and recurrent plaque groups. Recurrent plaques were matched with primary plaques by categories of stenosis, and differences in plaque features were compared between the 2 groups. RESULTS: Twenty-two recurrent lesions from 18 patients (14 unilateral and 4 bilateral) were classified as myointimal hyperplasia or recurrent plaque. Myointimal hyperplasia showed no difference in enhancement compared with normal post-carotid endarterectomy vessels (5 unilateral) but showed stronger enhancement than recurrent plaques (80.10% [SD, 42.42%] versus 56.74% [SD, 46.54%], P = .042). A multivariate logistic regression model of plaque-feature detection in recurrent plaques compared with primary plaques adjusted for maximum wall thickness revealed that recurrent plaques were longer (OR, 4.27; 95% CI, 1.32-13.85; P = .015) and more likely to involve a flow divider and side walls (OR, 6.96; 95% CI, 1.37-35.28; P = .019). Recurrent plaques had a higher prevalence of intraplaque hemorrhage (61.5% versus 30.8%, P = .048) by a χ2 test, but compositional differences were not significant in the multivariate model. CONCLUSIONS: Vessel wall MR imaging can distinguish recurrent plaques from myointimal hyperplasia and reveal features that may differ between primary and recurrent plaques, highlighting its value for evaluating patients with carotid restenosis.

Cell density mediated pericellular hypoxia leads to induction of HIF-1alpha via nitric oxide and Ras/MAP kinase mediated signaling pathways.

Environmental signals in the cellular milieu such as hypoxia, growth factors, extracellular matrix (ECM), or cell-surface molecules on adjacent cells can activate signaling pathways that communicate the state of the environment to the nucleus. Several groups have evaluated gene expression or signaling pathways in response to increasing cell density as an in vitro surrogate for in vivo cell-cell interactions. These studies have also perhaps assumed that cells grown at various densities in standard in vitro incubator conditions do not have different pericellular oxygen levels. However, pericellular hypoxia can be induced by increasing cell density, which can exert profound influences on the target cell lines and may explain a number of findings previously attributed to normoxic cell-cell interactions. Thus, we first sought to test the hypothesis that cell-cell interactions as evaluated by the surrogate approach of increasing in vitro cell density in routine normoxic culture conditions results in pericellular hypoxia in prostate cancer cells. Second, we sought to evaluate whether such interactions affect transcription mediated by the hypoxia response element (HRE). Thirdly, we sought to elucidate the signal transduction pathways mediating the induction of HRE in response to cell density induced pericellular hypoxia in routine normoxic culture conditions. Our results indicate that paracrine cell interactions can induce nuclear localization of HIF-1a protein and this translocation is associated with strong stimulation of the HRE-reporter activity. We also make the novel observation that cell density-induced activity of the HRE is dependent on nitric oxide production, which acts as a diffusible paracrine factor secreted by densely cultured cells. These results suggest that paracrine cell interactions associated with pericellular hypoxia lead to the physiological induction of HRE activity via the cooperative action of Ras, MEK1, HIF-1a via pericellular diffusion of nitric oxide. In addition, these results highlight the importance of examining pericellular hypoxia as a possible stimulus in experiments involving in vitro cell density manipulation even in routine normoxic culture conditions.

Vascular malformations.

Fourteen patients with hemangiomas or arteriovenous malformations treated with operative management are described. Particular emphasis is placed on the definition of terms and the methods of differentiating arteriovenous fistulas, hemangiomas, and arteriovenous malformations. Arteriovenous fistulas are acquired lesions consisting of a single communication. Hemangiomas are congential lesions that rarely pulsate or have an associated bruit; moreover by angiography they have multiple small feeding arterial vessels and histologically are composed of numerous thin-walled, but normal-appearing, blood vessels. Arteriovenous malformations are also congenital but they pulsate and have associated bruits; furthermore on angiography they have a number of larger arterial feeding vessels and histologically are composed of abnormal dysplastic vessels. Operative management of all lesions should be carefully planned and executed. Arteriovenous malformations and skeletal muscle hemangiomas will have a tendency to recur if not completely excised.

Treatment of acute methanol poisoning with fomepizole.

OBJECTIVE: To assess the efficacy and safety of fomepizole, a competitive alcohol dehydrogenase inhibitor, in methanol poisoning and to test the hypothesis that fomepizole obviates the need for hemodialysis in selected patients. DESIGN AND SETTING: Retrospective clinical study in three intensive care units in university-affiliated teaching hospitals. PATIENTS: All methanol-poisoned patients admitted to these ICUs and treated with fomepizole from 1987-1999 (n=14). MEASUREMENTS AND RESULTS: The median plasma methanol concentration was 50 mg/dl (range 4-146), anion gap 22.1 mmol/l (11.8-42.2), arterial pH 7.34 (7.11-7.51), and bicarbonate 17.5 mmol/l (3.0-25.0). Patients received oral or intravenous fomepizole until blood methanol was undetectable. The median cumulative dose was 1250 mg (500-6000); the median number of twice daily doses was 2 (1-16). Four patients underwent hemodialysis for visual impairment present on admission. Four patients with plasma methanol concentrations of 50 mg/dl or higher and treated without hemodialysis recovered fully. Patients without pretreatment visual disturbances recovered, with no sequelae in any case. There were no deaths. Fomepizole was safe and well tolerated, even in the case of prolonged treatment. Analysis of methanol toxicokinetics in five patients demonstrated that fomepizole was effective in blocking methanol's toxic metabolism. CONCLUSIONS: Fomepizole appears safe and effective in the treatment of methanol-poisoned patients. If our results are confirmed in prospective analyses, hemodialysis may prove unnecessary in patients presenting without visual impairment or severe acidosis.

Ulcer recurrence, morbidity, and mortality after operations for duodenal ulcer.

Due to fear of duodenal ulcer recurrence, PGV is not yet accepted by most surgeons in the United States as a satisfactory operation for treatment of intractable duodenal ulcer. Currently PGV has a 30 day operative mortality of 0.3 percent, a severe morbidity of 1 percent, and a long-term ulcer recurrence rate of about 11 percent. Truncal vagotomy and pyloroplasty has a mortality of 0.7 percent, a morbidity of 5 percent, and a recurrence rate of about 10 percent. Truncal vagotomy and antrectomy has a mortality of 1 percent, a morbidity of 5 percent, and a recurrence rate of about 2 percent. Thus, PGV is preferable to vagotomy and pyloroplasty since vagotomy and pyloroplasty has higher mortality and morbidity rates. The recurrence rate is similar. Furthermore, since postoperative morbidity is more difficult to manage than ulcer recurrence, a cogent argument can be made that PGV is superior to vagotomy and antrectomy as an operation for intractable duodenal ulcer.

The relative effects of lesser curvature vagotomy and esophageal vagotomy on the acid secretory effect of proximal gastric vagotomy.

Proximal gastric vagotomy is an operation consisting of division of all vagal fibers to the acid-secreting portion of the stomach. These fibers are usually divided along the lesser curvature of the stomach; however, because of a high rate of duodenal ulcer recurrence in some series, it has become apparent that it is important to divide the vagal fibers to the stomach leaving the main vagal trunks along the distal 5 cm of esophagus in order to achieve both adequate control of acid secretion and also a lower duodenal ulcer recurrence rate. The data presented in this study of ten mongrel dogs suggest that, in the dog, division of the vagal fibers along the lesser curvature is more important in reducing acid secretion than is esophageal vagotomy; but the data also emphasize the contribution of the vagal fibers along the distal esophagus since a marked reduction in 2 DG-stimulated acid secretion can only be achieved by dividing the vagal fibers around the distal esophagus as well as those along the lesser curvature.

Management of patients with hemangiomas and arteriovenous malformations.

Hemangiomas and AVMs are distinct congenital, benign, vascular lesions. Differentiation between the two is important because AVMs are amenable to embolization techniques and because patients with hemangiomas can be told they have a better prognosis than those with AVMs. A major error of management is to ligate the arterial blood supply to an AVM proximally, as the lesion will continue to grow, more collateral vessels will develop, and future angioaccess for purposes of evaluation or embolization will be denied. With care and prudence, many of these lesions can be successfully excised, or at least managed, so that the effect of these sometimes devastating lesions can be ameliorated.

Arteriovenous fistula simulating arteriovenous malformation.

A 36-year-old man was thought (for 20 years) to have an arteriovenous malformation that could not be excised. Repeated ligations of proximal arterial supply to the vascular lesion were only transiently beneficial and may have caused a delay in correct diagnosis because of impaired angioaccess. Once it was discovered that he had an arteriovenous fistula--probably caused by a tonsillectomy at age 6--it was possible to occlude the fistula with detachable balloons. The mass and his headaches subsequently resolved. AV fistulas are caused by trauma. Growth of AVMs is often stimulated by trauma. Both lesions have pulsatile masses associated with overlying bruits. The differential diagnosis can usually be made by arteriography, since AV fistulas are acquired lesions with a single communication between an artery and a vein, whereas AVMs are congenital lesions with multiple, large arterial feeding vessels and numerous arteriovenous communications. Proper diagnosis is important, since AVMs are aggressive lesions that tend to regrow if not completely excised. AV fistulas will be cured if the single arteriovenous communication can be obliterated. Proper treatment for AV fistula is obliteration of the single arteriovenous communication, operatively or with occlusive balloons; treatment of AVMs--when possible--is excision of the entire mass, combined (on occasion) with preoperative embolization of the tumor mass. This case report emphasizes the importance of accuracy in the differential diagnosis between arteriovenous malformations and arteriovenous fistulas; moreover, it demonstrates both the ineffectiveness and deleterious consequences of proximal arterial ligation, since collateral development is enhanced and angiographic access is compromised.

[Treatment of scabies and Ascabiol(®) supply disruption: what about the pediatric population?]. / Traitement de la gale et rupture d'Ascabiol(®) : quid de la population pédiatrique ? Gale chez l'enfant et rupture d'Ascabiol(®)

Scabies is a disease in steady increase in Île-de-France region. Standard treatment, Ascabiol(®) (benzyl benzoate/sulfiram), is back-order for several months and its return remains uncertain. Facing this drug shortage, French Drug Agency (ANSM) has imported a drug from Germany, Antiscabiosum 10 % (benzyl benzoate), to treat patients having contraindications for other scabicides available in France (ivermectin, esdepallethrine). However, infants less than 1 year (<15 kg) and asthmatics infants have no alternative treatment. A multidisciplinary workgroup explored the various existing therapeutic alternatives in France and worldwide. From ANSM's recommendations and group's experience, a decision algorithm was proposed for treating patients. However, pediatric context implied the use of off-label drugs. Proposed treatments widely known by practitioners, prescriptions-types, dose, modalities of use and dispensation, and flyers to patients were realized to optimize treatment efficacy.

Carotid plaque neovascularization and hemorrhage detected by MR imaging are associated with recent cerebrovascular ischemic events.

BACKGROUND AND PURPOSE: Pathologic studies suggest that neovascularization and hemorrhage are important features of plaque vulnerability for disruption. Our aim was to determine the associations of these features in carotid plaques with previous cerebrovascular ischemic events by using high-resolution CE-MRI. MATERIALS AND METHODS: Forty-seven patients (36 men; mean age 72.5 ± 10 years) underwent CE-MRI and MRA examinations for carotid plaque at 3T. IPH presence was recorded. Neovascularity was categorized by the degree of adventitial enhancement (0, absent; 1, <50%; 2, ≥50%). Reader variability was assessed by using weighted κ. Associations with events were determined by using multivariable logistic regression. RESULTS: Intra- and inter-reader agreement for grading adventitial enhancement were good to excellent. IPH was present in 49% of patients and was associated with events (P = .03). Patients grouped by categories 0, 1, and 2 adventitial enhancement had increasing frequencies of events (14% category 0, 48% category 1, 65% category 2; P = .02). Events were associated with IPH (OR, 10.18; 95% CI, 1.42-72.21) and adventitial enhancement (compared with category 0: OR, 14.90, 95% CI, 0.98-225.93 for category 1; OR, 51.17, 95% CI, 3.4-469.8 for category 2) after controlling for age, sex, cardiovascular risk factors, wall thickness, and stenosis. Stenosis was not associated with events. CONCLUSIONS: Adventitial enhancement and IPH are independently associated with previous events and may provide important insight into stroke risk not achievable by stenosis.

Identification of intraplaque hemorrhage on MR angiography images: a comparison of contrast-enhanced mask and time-of-flight techniques.

BACKGROUND AND PURPOSE: MRA is widely used to measure carotid narrowing. Standard CE- and TOF-MRA techniques use highly T1-weighted gradient-echo sequences that can detect T1 short blood products, so they have the potential to identify IPH, an indicator of plaque rupture. We sought to determine the accuracy and reliability of these MRA sequences to detect IPH. MATERIALS AND METHODS: 3D TOF and CE carotid MRA scans were obtained at 3T on 15 patients (age range, 58-86 years; 13 men) scheduled for CEA. The source images from the precontrast (mask) CE-MRA and the TOF sequences were reviewed by 2 independent readers for IPH presence (identified as hyperintense signal intensity compared with adjacent muscle). CEA specimens were stained with antibody against glycophorin A and Mallory stain to detect IPH and were correlated with MR images. RESULTS: Nine of 15 CEA specimens (61 of 144 MR images) contained IPH confirmed by histology. Compared with TOF, CE-MRA mask demonstrated greater sensitivity, specificity, PPV, and NPV for IPH detection. The accuracy for correctly identifying IPH by using CE-MRA mask images and TOF images was 94% and 84%, respectively. Inter- and intraobserver agreement for IPH detection was excellent by mask images (κ = 0.91 and κ = 0.94, respectively) and TOF images (κ = 0.77 and κ = 0.84, respectively). CONCLUSIONS: CE-MRA mask images are highly accurate and reliable for identifying IPH, more so than the TOF sequence, and can potentially provide valuable information about risk for rupture.

[Intracameral cefuroxime injections in prophylaxis of postoperative endophthalmitis after cataract surgery: implementation and results]. / Injections intracamérulaire de céfuroxime dans la prophylaxie des endophtalmies après chirurgie de cataracte: organisation et résultats.

INTRODUCTION: The European Society for Cataract and Refractive Surgery (ESCRS) endophthalmitis study demonstrated a significant decrease in the rates of postoperative endophthalmitis with the use of intracameral cefuroxime during cataract surgery. We report the organization of the implementation of this procedure in our departments and our results after 2 years. METHODOLOGY: All patients operated on for cataract between January 2007 and December 2008 in the ophthalmology departments of the Pellegrin University Hospital in Bordeaux and Lariboisiere University Hospital in Paris received an intracameral injection of cefuroxime at the end of the surgery. The cefuroxime was prepared in ready-for-use syringes by the hospital's central pharmacy. RESULTS: A convenient method of preparation and conditioning cefuroxime with stable preservation lasting longer than 1 week was set up in our hospitals. Between January 2007 and December 2008, out of 3316 patients who had a cataract surgery, two presented an endophthalmitis (0.06%). CONCLUSION: The intracameral cefuroxime injection at the end of the cataract surgery is a means to consider to prevent endophthalmitis. It can be implemented as a part of regular practice with appropriate preparation rules. The major barrier to its further use appears to be the lack of a commercially available preformulated preparation.

Anomalies of the inferior vena cava.

The inferior vena cava is formed by a complex process of embryogenesis during the sixth to tenth week of gestation. Improper completion of the process may result in four anatomic anomalies: duplication of the inferior vena cava, transposition or left-sided inferior vena cava, retroaortic left renal vein, and circumaortic left renal vein. The first two anomalies can be diagnosed by sonography and all four anomalies can be seen on CT scan of the abdomen. Duplication and transposition of the inferior vena cava should be further delineated by preoperative phlebography. Preoperative diagnosis of the anomalies should reduce the complication rate of abdominal aortic operations.