Pseudarthroses aseptiques des os longs [Pseudarthrosis of the long bones].

5 to 10% of all fractures present with a delayed union, whereas 1 to 5% progress to a nonunion, which can be defined as a fracture older than 6 months and lacks any potential to heal without any further intervention. Different fracture and patient related risk factors exist, and the management of a nonunion needs a thorough clinical, radiological and biological workup to classify them in one of the two main categories, the viable nonunions that need essentially more stability, usually by a more rigid fixation, and the non-viable nonunions that need essentially a biological stimulation by decortication and bone grafting. This treatment still remains the first choice with bony healing obtained in 85 to 95% of cases, but it also comes along with certain risks, and some valuable alternatives exist if chosen on the basis of rigid criteria.

Long-term effects of cannabis on brain structure.

The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich in cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study, we investigate (using Voxel-based Morphometry) gray matter changes in a group of regular cannabis smokers in comparison with a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with gray matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich in cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the 3 months before inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant gray matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger gray matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence.

Bilateral uveal pigmented alterations with remarkable evolution: long term follow-up in a case of possible bilateral diffuse uveal melanocytic proliferation

Purpose: to describe a case of probable bilateral diffuse uveal melanocytic proliferation (BDUMP) with scleral involvement, free from systemic malignancies and cataract. Methods: fifty months of follow up with recurrent complete ophthalmological examinations, including fundus photography, fluorescein/indocyanine green angiography (FA) and optical coherence tomography (OCT). Investigations also included an electroretinography (ERG) and histological examination of scleral biopsy. Extraocular malignancies were repeatedly searched. Results: the patient was a 61 year-old Italian man with chronic hepatitis type C. At first visit his best corrected visual acuity (BCVA) was 20/32 in OS and 20/25 in OD. Funduscopy showed multiple patch-shaped pigmented alterations involving macular region and mid retinal periphery. FA showed corresponding areas of late-phase hyperfluorescent pinpoints (figure 1a, OS) and intemediate-phase hypocyanescence (figure 1b, OS), with subtle serous neurosensory retinal detachment confirmed by OCT. Photopic and scotopic ERG tested normal. Systemic prednisone was administered for one month without any improvement. After ten months round pigmentary lesions appeared also in superior scleral surface of both eyes. Biopsy allowed to disclose slightly pigmented spindle cells. BCVA worsened for further 10 months, with enlargement of FA alteration areas but lenses still clear. After 30 months spontaneous coalescence and atrophy of retinal lesions started, paralleled by progressive visual recovery. At the end of our follow up BCVA was 20/25 in OU while scleral pigmentary lesions remained unchanged. Conclusions: we report the case of a patient with main features of BDUMP and some unusual findings. Although not all classical diagnostic criteria were fulfilled, the presence of scleral pigmented lesions and spontaneous visual recovery may enlarge clinical spectrum of the disease.

Uncontrollable hypertension in patients on hemodialysis: long-term treatment with captopril and salt subtraction

It has been suggested that an inappropriate relationship between renin and exchangeable sodium is responsible for the hypertension of patients with chronic renal failure. Long-term blockade of the renin system by captopril made it possible to test this hypothesis in 8 patients on maintenance hemodialysis. Captopril was administered orally in 2 daily doses of 25 to 200 mg. Previously, blood pressure averaged 179/105 +/- 6/3 (mean +/- SEM) pre- and 182/103 +/- 7/3 mm HG post-dialysis, despite intensive ultrafiltration and conventional antihypertensive therapy. The 4 patients with the highest plasma renin activity normalized their blood pressure with captopril alone, whereas in the 4 remaining patients, captopril therapy was complemented by salt subtraction which consisted in replacement of 1-2 liters of ultrafiltrate by an equal volume of 5% dextrose until blood pressure was controlled. After an average treatment period of 5 months, blood pressure of all 8 patients was reduced to 134/76 +/- 7/5 mm Hg (P less than 0.001) pre- and 144/81 +/- 9/5 mm Hg (P less than 0.001) post-dialysis without a significant change in body weight. The present data suggest that captopril alone or combined with salt subtraction normalizes blood pressure of patients on chronic hemodialysis with so called uncontrollable hypertension.

"Periodic crises": Clément Juglar between theories of crises and theories of business cycles

Business cycle theory is normally described as having evolved out of a previous tradition of writers focusing exclusively on crises. In this account, the turning point is seen as residing in Clément Juglar's contribution on commercial crises and their periodicity. It is well known that the champion of this view is Schumpeter, who propagated it on several occasions. The same author, however, pointed to a number of other writers who, before and at the same time as Juglar, stressed one or another of the aspects for which Juglar is credited primacy, including the recognition of periodicity and the identification of endogenous elements enabling the recognition of crises as a self-generating phenomenon. There is indeed a vast literature, both primary and secondary, relating to the debates on crises and fluctuations around the middle of the nineteenth century, from which it is apparent that Juglar's book Des Crises Commerciales et de leur Retour Périodique en France, en Angleterre et aux États-Unis (originally published in 1862 and very much revised and enlarged in 1889) did not come out of the blue but was one of the products of an intellectual climate inducing the thinking of crises not as unrelated events but as part of a more complex phenomenon consisting of recurring crises related to the development of the commercial world - an interpretation corroborated by the almost regular occurrence of crises at about 10-year intervals.

Long-term use and tolerability of irbesartan for control of hypertension.

In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150-300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics.

Poor value of pulsed-field gel electrophoresis to investigate long-term scale epidemiology of methicillin-resistant Staphylococcus aureus.

Pulsed-field gel electrophoresis (PFGE) is widely used for epidemic investigations of methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we evaluated its use in a long-term epidemiological setting (years to few decades, country to continent level). The clustering obtained from PFGE patterns after SmaI digestion of the DNA of 20 strains was compared to that obtained using a phylogenetic typing method (multiprimer RAPD). The results showed that the analysis of small PFGE bands (10-85kb) correlates better with multiprimer RAPD than the analysis of large PFGE bands (>85-700kb), suggesting that the analysis of small bands would be more suitable for the investigation of long-term epidemiological setting. However, given the technical difficulties to obtain a good resolution of these bands and the putative presence of plasmids among them, PFGE does not appear to be a method of choice for the long-term epidemiology analysis of MRSA.

Lapband Versus SAGB for Morbid Obesity. Long-Term Results of a Prospective Randomized Trial

Background: Gastric banding is currently one of the most performed procedures for morbid obesity. Results are related in part to the surgical technique and the quality of follow-up. Several bands are currently on the market, and it may bethat the type of band also plays a role in long-term results. The aim of this prospective randomized study was to compare the long-term results of the Lapband and the SAGB.Patients and methods: In three institutions with a common bariatric surgeon, consecutive patients undergoing laparoscopic gastric banding for morbid obesity were randomized to receive either a Lapband or a SAGB. The Lapband was placed using the perigastric and the SAGB with the pars flaccida technique. All data were collected prospectively. The median duration of follow-up was 131 months (103-147). Patients who lost their band were excluded from analysis as of band removal.Results: 180 patients were included between December 1998 and June 2002, 90 in each group. Except for age, which was lower in SAGB patients, the pre-operative characteristics were similar in the two patient groups. Early band-related morbidity was higher in the SAGB group (6,6 vs 0 %, p=0,03). Patients with a Lapband lost weight quicker than those with SAGB (EBMIL 50,8 vs 39,8 after 12 months, p<0,001), but the two weight loss curves joined after 24 months, and no difference could be observed later on up to 12 years after surgery (EBMIL 53,7 vs 58,1 % after 10 years, P=0,68). Long-term complications developed in 91 patients (50,5 %). Severe complications leading to band removal±conversion to another procedure developed in 30 and 40 patients in the Lapband and SAGB group respectively (33,3 vs 44,4 %, p=0,16).Conclusions: This prospective randomized study shows no significant difference in the long-term results of gastric banding between the Lapband and the SAGB. Both bands were associated with significant long-term complication and band removal/conversion rates. Patients who retain their band have acceptable long-term weight loss. It is likely that the concept of gastric banding rather than the device itself plays the most important role in longterm results.

Toward partial reorientation of land management for sustainability in view of material circulation: biophysical and historical analysis

This paper explores two major issues, from biophysical and historical viewpoints. We examine land management, which we define as the long-term fertility maintenance of land in relation to agriculture, fishery and forestry. We also explore humans’ positive role as agents aiming to reinforce harmonious materials circulation within the land. Liebig’s view on nature, agriculture and land, emphasizes the maintenance of long-term land fertility based on his agronomical thought that the circulation of matter in agricultural fields must be maintained with manure as much as possible. The thoughts of several classical economists, on nature, agriculture and land are reassessed from Liebig’s view point. Then, the land management problem is discussed at a much more fundamental level, to understand the necessary conditions for life in relation to land management. This point is analyzed in terms of two mechanisms: entropy disposal on the earth, and material circulation against gravitational field. Finally from the historical example of the metropolis of Edo, it is shown that there is yet another necessary condition for the sustainable management of land based on the creation of harmonious material cycles among cities, farm land, forests and surrounding sea areas in which humans play a vital role as agent.

Characterization of subpopulations (clones and subclones) of the 21 SF strain of Trypanosoma cruzi after long lasting maintenance in the laboratory

Several studies have shown a clonal structure of Trypanosoma cruzi and its possible correlation with the behavioral heterogeneity of the parasite strains. In the present study, the 21 SF strain, that have been maintained in laboratory by successive passages in mice, for more than 15 years, showing a stability of biological and isoenzymic characteristics has been cloned, with the objective of establishing the characters of its clones and subclones. With the technique of isolation of a single parasite from the blood of infected mice, 5 clones and 14 subclones have been obtained. After four passages into mice, inoculum of 10(5) was obtained for each clone and subclone and inoculated into mice weighing 10 to 12 g. These were used for the study of the biological behavior of the clones: evolution of parasitemia, morphology of blood forms and host mortality. For isoenzymic characterization, the clones and subclones were analyzed for ALAT, ASAT, GPI and PGM enzymes. Results have shown that the 5 clones and the 14 subclones disclosed a biological behavior similar to the parental strain, with minor variability of the parasitemic profiles and also the same isoenzymic patterns. These results confirm the stability of the 21 SF strain and indicate a clonal homogeneity of its populations. This is compatible with the hypothesis that the T. cruzi strains represent an equilibrium of either homogenous or heterogeneous populations.

Circulating microRNAs as long-term biomarkers for the detection of erythropoiesis-stimulating agent abuse.

MicroRNAs (miRNAs) are small, non-protein coding transcripts involved in many cellular and physiological mechanisms. Recently, a new class of miRNA called 'circulating miRNAs' was found in cell-free body fluids such as plasma and urine. Circulating miRNAs have been shown to be very stable, specific, and sensitive biomarkers. In this paper, we investigate whether circulating miRNAs can serve as biomarkers for erythropoiesis-stimulating agent abuse. To this end, we analyzed miRNA levels in plasma by miRNA microarrays and quantitative real-time polymerase chain reaction (PCR). Plasma samples are derived from a clinical study with healthy subjects injected with erythropoiesis-stimulating agent (C.E.R.A.). Based on microarray results, we observed a significant difference in the levels of miRNAs in plasma after C.E.R.A. injection. We demonstrated that a specific miRNA, miR-144, exhibit a high increase that lasts 27 days after C.E.R.A. stimulation. Considering the fact that miR-144 is an essential erythropoiesis agent in different organisms, these findings suggest the possibility of using miR-144 as a sensitive and informative biomarker to detect C.E.R.A. abuse. Copyright © 2011 John Wiley & Sons, Ltd.

Regional value added in Italy over the long run (1891-2001): linking indirect estimates with official figures, and implications

This paper presents value added estimates for the Italian regions, in benchmark years from 1891 until 1951, which are linked to those from official figures available from 1971 in order to offer a long-term picture. Sources and methodology are documented and discussed, whilst regional activity rates and productivity are also presented and compared. Thus some questions are briefly reconsidered: the origins and extent of the north-south divide, the role of migration and regional policy in shaping the pattern of regional inequality, the importance of social capital, and the positioning of Italy in the international debate on regional convergence, where it stands out for the long run persistence of its disparities.

Pilot study of induction chemotherapy followed by concomitant chemotherapy and IMRT or tomotherapy for nasopharyngeal carcinoma

Objective: Standard treatment of locally advanced (stages III and IV A-B) nasopharyngeal carcinoma (NPC) consists in chemoradiotherapy with 5-y survival rates of around 60%. However, acute toxicity prevents the administration of adequate adjuvant chemotherapy in nearly half of the patients. This situation has led to the hypothesis that induction chemotherapy followed by chemoradiotherapy may be a superior approach. Many ongoing studies are testing the role of induction chemotherapy in this setting. Newer radiotherapy techniques are becoming available (intensity modulated radiotherapy [IMRT] and tomotherapy). They can achieve a higher degree of accuracy in conforming the radiation to the planned target volume while sparing normal tissue resulting in less acute and long-term toxicity. Methods: We report here our local experience of 11 consecutive locally advanced NPC patients treated between June 2004 and October 2007. Median age was 46 years (range, 17-65). All but one were male patients. Initial stage was stage III in 5, and stage IVA-B in 6 patients. Treatment consisted of 3 cycles of induction TCF (Docetaxel 75 mg/m2- Cisplatin 75 mg/m2- 5-fluorouracil 750 mg/m2/d 5 days) chemotherapy followed by concomitant chemoradiotherapy with 3 cycles of cisplatin (100 mg/m2), or carboplatin (AUC 5) in case of renal impairment. Radiotherapy was delivered by either IMRT or tomotherapy. Macroscopic disease (tumor + involved lymph nodes) was treated with 70 Gy, 2 Gy/fraction (IMRT), or 69.6 Gy, 1.12 Gy/fraction (simultaneus integrated boost [SIB] technique). Elective nodal irradiation of 46-54 Gy lymph was performed in all patients, whereas elective irradiation of the entire nasopharynx (60 Gy) half of patients. Results: All but one tumor were EBV positive. Induction chemotherapy was done as planned for 8 patients (73%). Two patients had only 2 cycles, 1 patient had only1 cycle of TCF, and the other without docetaxel. Concomitant chemotherapy was given as planned in 7 patients (64%). Four patients had only 2 cycles. Radiotherapy could be delivered as planned in all patients. Eight weeks post treatment all patients proved to have a CR (CR or uCR). After a median follow-up of 11 months (range, 6-38 months) only one patient has relapsed. Details on acute and 1 year toxicities will be presented. Conclusion: Treatment of locally advancedNPC with induction and concomitant chemotherapy is feasible and well tolerated. The use of IMRT or tomotherapy technique seems to ameliorate the therapeutic index particularly in regard with xerostomia. All our patients presented a complete response. For the assessment of survival and long-term toxicity, a longer follow-up period is needed.

No news in business cycles

This paper uses a structural, large dimensional factor model to evaluate the role of 'news' shocks (shocks with a delayed effect on productivity) in generating the business cycle. We find that (i) existing small-scale VECM models are affected by 'non-fundamentalness' and therefore fail to recover the correct shock and impulse response functions; (ii) news shocks have a limited role in explaining the business cycle; (iii) their effects are in line with what predicted by standard neoclassical theory; (iv) the bulk of business cycle fluctuations are explained by shocks unrelated to technology.