[Proposal of guidelines for antibiotic prophylaxis in plastic, reconstructive, and aesthetic surgery]. / Proposition de recommandations sur l'antibioprophylaxie en chirurgie plastique, reconstructrice et esthétique.

BACKGROUND: In plastic surgery, guidelines about antibiotic prophylaxis are inaccurate and incomplete, due to result the absence of high-level studies on this subject. The main aim is to establish national common recommendations for plastic surgery antibiotic prophylaxis. MATERIALS AND METHODS: A working group will discuss and validate a multi-center analysis of practices in three University Hospital Centers compared to an interdisciplinary analysis of recommendations to the French Society of Anaesthesia and Intensive Care Medicine and scientific literature. This working group is composed of plastic surgeon members of the French Society of Aesthetic Reconstructive Plastic Surgery, infectious disease physicians, and anaesthesiologists to define clear and precise antibiotic prophylaxis recommendations. RESULTS: Antibiotic prophylaxis with cefazoline (or clindamycine±gentamicine in case of allergy), has been recommended for general surgery with flap or implants, for breast surgery, lipofilling, and rhinoplasty. In other plastic surgery, no antibiotic prophylaxis has been recommended. CONCLUSION: We established common recommendations for plastic surgery antibiotic prophylaxis that is the first step to update these recommendations. Now, they can be evaluated in clinical situation to validate them.

[Free latissimus dorsi flap lacing and local care in two-stage scalp reconstruction]. / Laçage de lambeau libre de grand dorsal dans le cadre des soins locaux d'un lambeau en nourrice du cuir chevelu.

Surgical treatment of large and multiple lesions of irradiated scalp may require subtotal scalp exeresis and reconstruction in two-stage free flap surgery: harvesting and placing the flap first, then scalp removing and defect covering in a second step. This strategy raises the question of how to care the flap between the two surgeries. We report an original technique of free latissimus dorsi flap lacing. A 70-year-old male, afflicted with familial cylindromatosis and treated by brachytherapy 18years ago, received a free latissimus dorsi myocutaneous flap in two-stage surgery, allowing 25×25cm pathological scalp exeresis. During first step, suture clips were fixed in two rows around the future scalp defect, in order to be used as anchors for the flap lacing. Braided wire were chosen for a better steerability, and to prevent knots untightening. Thus, the flap were placed in "anatomical" place, next to the scalp, pending secondary procedure. This situation permitted to avoid flap or pedicle compression or plication, and to ease flap care. The wires were tighten as shoelaces, allowing them to be undone and done as desired. The two-stage free latissimus dorsi flap reconstruction of scalp large defect permitted us to assess the flap reliability before final reconstruction. The lacing solution allowed us regular local care and convenient flap handling, while favoriting its optimal placing next to its future location.

Full-thickness skin grafts for lower leg defects coverage: Interest of postoperative immobilization.

INTRODUCTION: Full-thickness skin graft is an effective reconstruction method after excision of skin lesions on the lower limb that are not amenable to primary closure. The randomness of graft take is the major drawback of this procedure. OBJECTIVE: The objective of the study was to evaluate the outcome of full-thickness skin grafts (FTSG), used to repair lower leg defects after excision of skin lesions, after a 5-day immobilization period. MATERIAL AND METHODS: All consecutive patients who underwent FTSG to cover defects below the knee between November 2011 and January 2016 were retrospective reviewed. Graft take was assessed and defined as good (>90% graft take), moderate (between 50% and 90% graft take), or poor (<50% graft take). RESULTS: Seventy patients were included. Median age was 70 years (range, 18-92 years). The median area of the defect was 12cm2. Graft take was good in 64 patients (91.4%), moderate in 3 patients (4.3%), and poor in 3 patients (4.3%) at Day 5. Complications included hematoma (11%), infection (14%) and venous thrombosis (3%). CONCLUSION: Full-thickness skin graft is a reliable method to repair defects on the lower leg after removal of skin lesions. A 5-day immobilization period can improve the graft take. The authors have indicated no significant interest with commercial supporters.

Relevance of intraoperative indocyanine green injection in breast reconstruction using DIEP procedure for abdominal scars.

PURPOSE OF THE STUDY: The presence of midline sub-umbilical and/or suprapubic scar can sometimes hinder breast reconstruction using deep inferior epigastric perforator (DIEP) procedure. BASIC PROCEDURES: We report the use of indocyanine green injection in a 60-year-old woman in the context of deep inferior epigastric perforator (DIEP) procedure for unilateral breast reconstruction (bilateral breast cancer) with abdominal scar (midline sub-umbilical scar and Pfannenstiel incision scar). MOST IMPORTANT FINDINGS: This technique underlines the importance of neoangiogenesis mechanisms and helped simplify the surgical gesture initially planned (in order to ensure volume in spite of the scars as a DIEP procedure with double anastomoses was initially planned). PRINCIPAL CONCLUSIONS: This intraoperative vascular imaging technique is a minimally invasive, simple and quick procedure allowing the precise visualization of vascularized territories.

[Cayler syndrome: A case report and review of the literature]. / Syndrome de Cayler : à propos d'un cas et revue de la littérature.

BACKGROUND AND PURPOSE: Facial asymmetries to the tears are rare. We report a pediatric original case that may fall within the framework of a Cayler syndrome. Through its clinical presentation, we will discuss differential diagnoses, associated forms, its etiology, and its management. CASE REPORT: At the maternity unit, in a male infant, after vaginal delivery at term without extraction, was discovered a lack of mobility of the labial commissure on the right side, only when crying. The rest of the examination was unremarkable, except ipsilateral microtia. Genetically, karyotype was 46,XY, 22q11 without microdeletion. The head and neck MRI and echocardiogram were normal. DISCUSSION AND CONCLUSION: Asymmetry with tears has been described in the literature, through association with microdeletion 22q11 syndrome. The originality of this case was the presence of an isolated muscle abnormality. Muscles affected by this syndrome are: Musculus depressor labii inferioris, the Depressor anguli oris, and Mentalis musculus. The three muscles can be affected concomitantly. Isolated involvment of the Depressor anguli oris muscle has also been described. The mechanical dysfunction can be either linked to muscle innervation agenesis or to a defect thereof. There is no specific treatment. The symptoms improve with age by decreasing the frequency of crying. However, it is important to know this pathology in order to seek an optimum balance further in search of associated abnormalities (FISH 22q11, cardiac Doppler ultrasound) but also to educate, to reassure families often worried by the situation.

[The role of balneology in plastic surgery]. / Place du thermalisme en chirurgie plastique.

UNLABELLED: Balneology can be part of the plastic surgery care sector. The objectives of this study were firstly to the state of knowledge about the hydrotherapy and specify the place reserved for hydrotherapy by surgeons as an adjunct in plastic and reconstructive surgery (adult and child). MATERIALS AND METHODS: Multicentric national study by poll (Google Drive®) focused at plastic and/or pediatric surgeons. The following information was analyzed: frequency, timing of prescription, indications, the surgeon's feelings towards hydrotherapy and the differences between adult's and children's prescriptions. RESULTS: Fifty-four teams were contacted: 22 responses were received (15 "adult" plastic surgeons, 9 "pediatric" plastic surgeons, 6 pediatric surgeons, with 12 out of 22 working with burnt patients). Eighteen out of 22 prescribed hydrotherapy. Twenty out of 22 thought that hydrotherapy had a role as adjuvant therapy in plastic surgery. The indications were: burns (11/20), skin-graft hypertrophy (10/20), inflammatory and pruritic scar and cutaneous trophic disorders (9/20), psychological (3/20), retractions (2/20), weight loss and smoking (1/20). The timing of the prescription was: < 3 months (2/20), < 6 months (7/20), > 6 months and < 1 year (15/20), > 1 year (8/20) after surgery/trauma. Twenty out of 22 found a beneficial effect: physical (19/20): reduction of inflammatory signs, pruritus and pain, scar maturation, skin thinning improvement; psychological (14/20): positive for patient/family. Five out of 17 made the difference between child/adult, 10/17 made no difference but only treated adults or children. CONCLUSION: The respondents in the study are probably more sensitive to the effects of hydrotherapy that non-respondents. It is difficult to assess the real impact of hydrotherapy in plastic surgery because distinguishing spontaneous favorable evolution of a scar from one only due to the hydrotherapy or multidisciplinary management is difficult. However, hydrotherapy seems to have its role among multidisciplinary management.

[Umbilicus in children]. / L'ombilic chez l'enfant.

The umbilicus is our first scar. It is the last remain of our life in utero. Besides the umbilical hernia, a common pathology during the first three years of life that rarely requires surgery, there are some rare congenital abnormalities such as gastroschisis and omphalocele, which occur in about 1-5/10,000 births. Gastroschisis is a birth defect of the anterior abdominal wall, through which the fetal intestines freely protrude and are not covered by any membranes. During the 13th week prenatal ultrasound, the umbilical cord can be seen to be properly attached while the intestines float freely in the amniotic fluid. This defect is most common in young women who smoke and/or use cocaine and is not typically associated with genetic disorders. Omphalocele is an average coelosomy, in which a visceral hernia protrudes into the base of the umbilical cord. Omphalocele is typically diagnosed during the prenatal phase, and occurs most commonly in older mothers. It is frequently associated with genetic and morphologic abnormalities, therefore a karyotype should automatically be performed. For these two pathologies, the surgical problem lies in managing, during the reintegration, the conflict container/content responsible to lower vena cava syndrome and disorders ventilatory. Deciding on the technique will depend on the clinical form, and on the tolerance to reinsertion. The success of the surgery is directly linked to the postoperative emergence care for the pre-, per- and postnatal phases. The umbilical cord is preserved in the case of a gastroschisis. A primary or secondary umbilicoplasty will be performed for an omphalocele closure. The umbilicoplasty aims to create an umbilicus in a good position by giving it a shape, ideally oval, but also and especially an umbilication. The primary or secondary umbilicoplasty remains a challenge in a growing abdomen (change in position, deformation, loss of intussusception with growth). Many techniques are described: cutaneous flaps randomly placed, excision and skin plasty, resection and controlled wound healing. The choice of technique is a matter of practice but must be done in a rational way, depending on the scar condition when secondary reconstruction, and with minimal scarring, for primary reconstruction. To avoid morphological changes associated with growth, secondary umbilicoplasty should be proposed after the age of five.

Dipolar motions and ionic conduction in an ibuprofen derived ionic liquid.

It was demonstrated that the combination of the almost water insoluble active pharmaceutical ingredient (API) ibuprofen with the biocompatible 1-ethanol-3-methylimidazolium [C2OHMIM] cation of an ionic liquid (IL) leads to a highly water miscible IL-API with a solubility increased by around 5 orders of magnitude. Its phase transformations, as crystallization and glass transition, are highly sensitive to the water content, the latter shifting to higher temperatures upon dehydration. By dielectric relaxation spectroscopy the dynamical behavior of anhydrous [C2OHMIM][Ibu] and with 18.5 and 3% of water content (w/w) was probed from well below the calorimetric glass transition (Tg) up to the liquid state. Multiple reorientational dipolar processes were detected which become strongly affected by conductivity and electrode polarization near above Tg. Therefore [C2OHMIM][Ibu] exhibits mixed behavior of a conventional molecular glass former and an ionic conductor being analysed in this work through conductivity, electrical modulus and complex permittivity. The dominant process, σα-process, originates by a coupling between both charge transport and dipolar mechanisms. The structural relaxation times were derived from permittivity analysis and confirmed by temperature modulated differential scanning calorimetry. The temperature dependence of the ß-secondary relaxation is coherent with a Johari-Goldstein (ßJG) process as detected in conventional glass formers.

A comparative study of ibuprofen and ketoprofen glass-forming liquids by molecular dynamics simulations.

In this paper, structural and dynamical properties of ibuprofen and ketoprofen glass-forming liquids have been investigated by means of molecular dynamics simulations. Molecular mobility of both materials is analyzed with respect to the different inter-molecular linear/cyclic hydrogen bonding associations. For ibuprofen, the dominant organization is found to be composed of small hydrogen bonding aggregates corresponding to cyclic dimers through the carboxyl group. For ketoprofen, the propensity of cyclic dimers is significantly reduced by the formation of hydrogen bonds with the ketone oxygen of the molecule altering the hydrogen bond (HB) associating structures that can be formed and thus molecular dynamics. The issue of the presence/absence of the peculiar low frequency Debye-type process in dielectric relaxation spectroscopy (DRS) data in these materials is addressed. Results obtained from simulations confirm that the Debye process originates from the internal cis-trans conversion of the -COOH carboxyl group. It is shown that the specific intermolecular HB structures associated to a given profen control the main dynamical features of this conversion, in particular its separation from the α-process, which make it detectable or not from DRS. For ibuprofen, the possible role of the -CCCO torsion motion, more "local" than the -COOH motion since it is less influenced by the intermolecular HBs, is suggested in the microscopic origin of the quite intense secondary γ-relaxation process detected from DRS.

[Split-thickness skin graft donor site: which dressing use?]. / Site donneur de greffe de peau mince : quel pansement utiliser ?

INTRODUCTION: The management of split-thickness skin graft donor sites is targeted towards promoting the healing process, reducing pain. This has been an inconclusive topic. The aim of this study was to list and to discuss the French practices in term of split-thickness skin graft (STSG) donor site dressing. MATERIALS AND METHODS: Multicentric national study by questionnaire (Google Drive(®)) for the attention of the plastic and/or pediatric surgeons. The type of dressing used on skin and sclap and the rhythm of dressing changes were analyzed. RESULTS: The study included 26 surgical centers on 40 contacted. The alginate is mainly used (Algostéril(®)) (17/26). It is left in position until healing (13/17). Five other types of dressings have been reported: paraffin gauze (3/26), lipidocolloides (1/26), Mepitel(®) (1/26), Mepilex(®) (1/26), indifferent use of gauze or alginate dressings (4/26). Twenty-two out of 26 centers make no difference in dressing choice between skin and scalp. Medical practices did not differ between adult or pediatric departments. CONCLUSION: Cost-effectiveness has become an important issue in wound management, requiring judicious use. The lack of consensus regarding split-thickness skin graft donor site dressing and our clinical practices force us to reconsider the best therapeutic option. This study coupled with the analysis of the literature highlights the difficulties of the practitioner in choosing the best dressing. The alginate seems to get the preference of our practices by its ease of use, its absence of change (reduces pain by limiting manipulations) and its moderate cost.

Molecular mobility of amorphous S-flurbiprofen: a dielectric relaxation spectroscopy approach.

Amorphous S-flurbiprofen was obtained by the melt quench/cooling method. Dielectric measurements performed in the isochronal mode, conventional and temperature modulated differential scanning calorimetry (TMDSC) studies showed a glass transition, recrystallization, and melting. The different parameters characterizing the complex molecular dynamics of amorphous S-flurbiprofen that can have influence on crystallization and stability were comprehensively characterized by dielectric relaxation spectroscopy experiments (isothermal mode) covering a wide temperature (183 to 408 K) and frequency range (10(-1) to 10(6) Hz): width of the α-relaxation (ßKWW), temperature dependence of α-relaxation times (τα), fragility index (m), relation of the α-relaxation with the ß-secondary relaxation, and the breakdown of the Debye-Stokes-Einstein (DSE) relationship between the structural relaxation time and dc-conductivity (σdc) at deep undercooling close to Tg. The ß-relaxation, observed in the glassy as well as in the supercooled state was identified as the genuine Johari-Goldstein process, attributed to localized motions and regarded as the precursor of the α-relaxation as suggested in the coupling model. A separation of about 6 decades between the α- and ß-relaxation was observed at Tg; this decoupling decreased on increasing temperature, and both processes merged at Tαß = 295 K. The temperature dependence of the α-relaxation time, τα, was described by two Vogel-Fulcher-Tammann-Hesse equations, which intercept at a crossover temperature, TB = 290 K, close to the splitting temperature between the α- and ß-relaxation. From the low temperature VFTH equation, a Tg(DRS) = 265.2 was estimated (at τα =100 s) in good agreement with the calorimetric value (Tg,onset,TMDSC = 265.6 K), and a fragility or steepness index m = 113 was calculated allowing to classify S-flurbiprofen as a fragile glass former. The α-relaxation spectra were found to be characterized by a relatively large degree of nonexponentiality (ßKWW = 0.52). A breakdown of the DSE log10 σdc - log10 τ relation was observed revealing an enhancement of translational ionic motions in comparison with the orientational molecular motions as the glass transition temperature Tg is approached from above.

Leucocytosis in women with polycystic ovary syndrome (PCOS) is incompletely explained by obesity and insulin resistance.

OBJECTIVES: Low-grade chronic inflammation predicts cardiovascular outcomes and is observed in women with polycystic ovary syndrome (PCOS). Whether this is entirely a cause or consequence of insulin resistance (IR) is unknown. METHODS: Seventy pairs of women with and without PCOS, matched for age, body mass index (BMI) and IR (HOMA, QUICKI and Avignon index), were generated from a larger cohort of 103 women with and 104 BMI-matched women without PCOS. Women with PCOS were studied in the follicular phase of the menstrual cycle. White cell count (WCC), high-sensitivity CRP (hsCRP) and a series of 12 cytokines and growth factors were measured. These inflammatory markers were also compared between women with PCOS and 10 normal women studied in the follicular, peri-ovulatory and luteal stages. RESULTS: When all subjects were compared, WCC (6.75 × 10(9) vs 5.60 × 10(9 ) g/l, P < 0.005), hsCRP (4.04 vs 2.90 mg/l, P < 0.05) and IL-6 (1.11 vs 0.72 pg/ml, P < 0.05) were greater in women with PCOS. Pair-matching for IR eliminated between-group differences in hsCRP and cytokines but did not alter the difference in WCC (6.60 × 10(9) vs 5.60 × 10(9 ) g/l, P < 0.005). WCC was greater in PCOS compared to normal women at all stages of the menstrual cycle. CONCLUSIONS: Low-grade inflammation occurs in PCOS. Increased hsCRP and cytokines are associated with IR, but increased WCC is observed even when IR is accounted for. The explanation for this and its clinical significance is unknown.

Impact of temperature on immediate and secondary compression of MSW with high and low food contents.

Landfills in developing countries usually show municipal solid wastes (MSW) with large amount of food wastes, extraordinarily high moisture contents, and high internal temperatures. Because of these specific characteristics, significant post-closure settlements in landfills with high food waste are expected over time. This paper focused on the assessment of temperature impact on immediate and secondary compression behaviors of MSW with large contents of food, water, and plastic, comparatively to an aged low food content waste. A compression test was developed having a temperature-control system. The immediate compression index (C'c) of HFWC samples was found to be higher than those of low food waste content (LFWC) owing to the soft behavior of food content, although immediate compression was 15-30% of total strains for HFWC wastes, while for LFWC samples it was 80% of total strains. Mechanical creep was also greater in HFWC owing to the soft behavior of the wet food components intensified by temperature increases. Mechanical creep of LFWC samples was attributed to the deformation of large parcel of soft plastics, also accelerated by temperature. The HFWC waste showed a first dominant phase of biocompression with an intense and rapid biological degradation, and a second phase characterized by reduced biological activity. Temperatures higher and high compression stresses are required to provide significant impact on biocompression index magnitudes. Overall, the compressibility of high food content wastes has shown to be significantly higher and the temperature impact led to twice total settlements of the MSW with low organic content.

Polymorphism and stability of ibuprofen/nicotinamide cocrystal: The effect of the crystalline synthesis method.

The development over the past decade of design strategies for cocrystal preparation have led to numerous methods for the synthesis of cocrystal without take care of their influence on the precise structure and stability of cocrystalline states. On the other hand the mechanism of cocrystal formation remains widely unclear, especially the identification of the type of interactions mostly responsible for the cocrystalline stability. The present study focuses on the influence of the crystalline synthesis method on the polymorphism of cocrystals was analyzed from the preparation of S-ibuprofen/nicotinamide and RS-ibuprofen/nicotinamide cocrystals by co-milling, slow solvent evaporation and crystallization from the melt. X-ray diffraction and Raman spectroscopy experiments have shown that the polymorphic form of the cocrystals obtained by recrystallization from the melt (Form A) is different from that prepared by milling and by slow evaporation in solution (Form B). It was shown that both isothermal and non-isothermal recrystallizations from the melt blending are observed via a transient metastable micro/nano structure of form A. Additionally, it was observed that form A transforms into Form B upon heating via very weak changes in the hydrogen bond network. The crystallization in form A from the melt, instead of form B by other methods, was explained by the difficulty to form a supramolecular organization too far energetically from that existing in the melt. This study shows the crucial role of supramolecular H-bonding on the formation mechanism of cocrystals and how does the synthesis method of cocrystals change the supramolecular organization and the related structure of cocrystals.

Endothelium-derived nitric oxide is involved in the hypotensive and vasorelaxant effects induced by discretamine in rats.

The aim of this study was to investigate the pharmacological effects of discretamine, an isoquinoline alkaloid isolated from Duguetia magnolioidea Maas, on the cardiovascular system, using a combined in vivo and in vitro approach. Blood pressure and heart rate measurements, as well as changes in isometric tension in rat superior mesenteric arterial rings, elicited by discretamine were recorded. In normotensive non-anaesthetized rats (n = 6), discretamine (0.01; 0.05; 0.1; 0.5; 1, 5 and 10 mg/kg i.v., randomly) injections produced hypotension (-5.2 +/- 1.7; -5.1 +/- 2.1; -7.7 +/- 2; -8.9 +/- 1.7; -9.6 +/- 2.2; -16.8 +/- 2.8 and -13.4 +/- 1.3 mmHg, respectively) accompanied by tachycardia (24.2 +/- 6.1; 36.8 +/- 11.3; 44.2 +/- 7.7; 45.9 +/- 6.4; 48.2 +/- 9.1; 72.1 +/- 14.5 and 64 +/- 17 bpm, respectively). Hypotensive and tachycardic responses were significantly attenuated after L-NAME (20 mg/kg, i.v.) administration. In isolated rat mesenteric artery rings, with endothelium intact, discretamine (10(-12) - 10(-5) M) induced concentration-dependent relaxation of the contractions induced by phenylephrine (10 microM) [pD2 = 6.8 +/- 0.1]. The effect of the discretamine on phenylephrine induced contractions was significantly attenuated after removal of the vascular endothelium [pD2 = 5.8 +/- 0.04]. Similar results were obtained after pre-treatment with L-NAME 100 microM [pD2 = 5.8 +/- 0.04], L-NAME 300 microM [pD2 = 5.9 +/- 0.06], Hydroxocobalamin 30 microM [pD2 = 5.8 +/- 0.06] or ODQ 10 microM [pD2 = 5.8 +/- 0.04]. In addition, in rabbit aorta endothelial cell line, discretamine significantly increased NO3- levels. These results suggest that the hypotensive effect induced by discretamine is probably due to a peripheral vasodilatation, at least, in part, due to the release of NO from vascular endothelium and consequent activation of soluble guanylyl cyclase (GC) in the vascular smooth muscle cells.

Tuberculosis teaching in Brazilian medical schools.

To achieve tuberculosis (TB) control, National Tuberculosis Programme guidelines should be implemented effectively. In a survey conducted in 2005-2006, 33 Brazilian medical school coordinators answered a questionnaire about TB education. The median time dedicated to TB was 27 h (4-119 h), spread over several disciplines, mainly biological and clinical. This included 12 h (0-88 h) of practical activities, mainly in university hospitals (53%). The recommendation to offer human immunodeficiency virus testing for TB patients was taught in only 54% of the schools. TB education in Brazil is fragmented and restricted to a biological approach, while field activities are insufficient and carried out in inadequate settings. Important changes to the TB curriculum are necessary.

Risk of endometrial cancer following estrogen replacement with and without progestins.

BACKGROUND: Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we examined the endometrial cancer risk associated with combined estrogen-progestin regimens currently in use, since the safety profiles of these regimens have not been clearly defined. METHODS: We conducted a nationwide population-based, case-control study in Sweden of postmenopausal women aged 50-74 years. We collected information on use of hormone replacement from 709 case patients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as estimates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens. RESULTS: Treatment with estrogens alone was associated with a marked duration- and dose-dependent increase in the relative risk of endometrial cancer. Five or more years of treatment had an OR of 6.2 for estradiol (95% confidence interval [CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Following combined estrogen-progestin use, the association was considerably weaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with cyclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use). CONCLUSION: The risk of developing endometrial cancer is increased after long-term use of estrogens without progestins and with cyclically added progestins. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.

Stem Cell Leukemia: how a TALented actor can go awry on the hematopoietic stage.

TAL1/SCL/TCL5 is a critical transcription factor for hematopoietic stem cell maintenance and regulation of early hematopoiesis. However, aberrant expression of TAL1 in committed T-cell precursors is also directly implicated in the development of T-cell leukemia. Roughly 25 years ago TAL1 was identified in early hematopoietic cells and involved in leukemia. Here, we review the wealth of knowledge gained since then on its physiological roles and mechanisms by which TAL1 ectopic expression contributes to leukemogenesis. We emphasize recent findings that shed light into the intricacies of TAL1 (epi)genetic regulation and the transcription network orchestrated by this major T-cell oncogene. Importantly, an exciting time is coming when data using the mechanistic knowledge accumulated on TAL1 may be used to develop novel anti-leukemia targeted therapies.

Excess mortality in bipolar and unipolar disorder in Sweden.

BACKGROUND: Selected groups of patients with bipolar and unipolar disorder have an increased mortality rate from suicide and natural causes of death. However, there has been no population-based study of mortality of patients followed up from the onset of the illness. METHODS: All patients with a hospital diagnosis of bipolar (n = 15 386) or unipolar (n = 39 182) disorder in Sweden from 1973 to 1995 were identified from the inpatient register and linked with the national cause-of-death register to determine the date and cause of death. Overall and cause-specific standardized mortality ratios (SMRs) and numbers of excess deaths were calculated by 5-year age classes and 5-year calendar periods. RESULTS: The SMRs for suicide were 15.0 for males and 22.4 for females with bipolar disorder, and 20.9 and 27.0, respectively, for unipolar disorder. For all natural causes of death, SMRs were 1.9 for males and 2.1 for females with bipolar disorder, and 1.5 and 1.6, respectively, for unipolar disorder. For bipolar disorder, most excess deaths were from natural causes, whereas for unipolar disorder, most excess deaths were from unnatural causes. The SMR for suicide was especially high for younger patients during the first years after the first diagnosis. Increasing SMR for suicide during the period of study was found for female patients with unipolar disorder. CONCLUSIONS: This population-based study of patients treated in the hospital documented increased SMRs for suicide in patients with bipolar and unipolar disorder. The SMR for all natural causes of death was also increased, causing about half the excess deaths.